DigitalUM :: Browsing by Subject "Colorectal cancer"

Browsing by Subject "Colorectal cancer"

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Open Access
A new practical classification of desmoplastic reaction in endoscopic forceps biopsy of colorectal cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Jing, Haiyan; Shang, Liang; Zhao, Shulei; Yao, Zhigang; Lv, Beibei; Zhu, Xiaolong
Background. The histopathological discrepancy between endoscopic forceps biopsy (EFB) and post-resection specimens is considered a practical clinical problem. This retrospective study aimed to determine the current diagnostic concordance between the EFB and surgical specimens of colorectal cancer (CRC) and then investigated the useful factors in EFB diagnosis. Methods. We used the representative pathological data of 2188 CRCs. The comparison of histopathological discrepancy between EFB and the related surgical specimens was performed. Furthermore, 418 biopsy specimen slides in our hospital were reviewed to determine the classification of intratumor desmoplastic reaction (DR). Results. Among the 2188 patients, the positive sensitivity of EFB for adenocarcinoma was 82.7%. The discrepancy rate between the EFB and surgical specimens was 10.8-40.0% corresponding to different T stages. On the basis of DR classification, 32, 131, and 255 tumors were categorized as little, moderate and extensive, respectively. The correlation between DR classification and tumor invasion based on T stage was significant (Spearman's rho= 0.112; p<0.05). The extensive DR provided better estimates for advanced tumors than the little and moderate DR (χ2= 3.977, p=0.046). Besides DR, factors including deeper cutting the slides and histological types were significantly associated with "adenocarcinoma" diagnosis in EFB of CRCs (p<0.05). Conclusion. To the best of our knowledge, this is the first time that a DR classification specifically for EFB specimens was proposed. It might contribute to improve the accuracy of biopsy-based diagnosis of CRC.
Open Access
Aging, methylation and cancer
(2000) Ahuja, N.; Issa, J.-P.J.
Alterations in methylation are widespread in cancers. DNA methylation of promoter-associated CpG islands is an alternate mechanism to mutation in silencing gene function, and affects tumor-suppressor genes such as p16 and RBl, growth and differentiation controlling genes such as ER and many others. Evidence is now accumulating that some of these methylation changes may initiate in subpopulations of normal cells as a function of age and progressively increase during carcinogenesis. Age-related methylation appears to be widespread and is one of the earliest changes marking the risk for neoplasia. In colon cancer, we have shown a pattern of age-related methylation for several genes, including ER, IGF2, N33 and MyoD, which progresses to full methylation in adenomas and neoplasms . Hypermethylation of these genes is associated with gene silencing. Age-related methylation involves at least 50% of the genes which are hypermethylated in colon cancer, and we propose that such age-related methylation may partly account for the fact that most cancers occur as a function of old age. Age-related methylation, then, may be a fundamental mark of the field defect in patients with neoplasia. The causes of age-related methylation are still unknown at this point, but evidence points to an interplay between local predisposing factors in DNA (methylation centers), levels of gene expression and environmental exposure. The concept that age-related methylation is a predisposing factor for neoplasia implies that it may serve as a diagnostic risk marker in cancer, and as a novel target for chemoprevention. Studies in animal models support this hypothesis and should lead to novel approaches to risk-assessment and chemoprevention in humans.
Open Access
Aldehyde dehydrogenase 1B1 is a potential marker of colorectal tumors
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Wang, Hejing; Li, Yanmeng; Zhou, Donghu; Li, Xiaojin; Jia, Siyu; Qi, Saiping; Huang, Jian
Colorectal cancer (CRC) is common worldwide. Aldehyde dehydrogenase 1B1 (ALDH1B1), a member of the ALDH1 family, serves as a biomarker for cancer stem cells. We hypothesized that ALDH1B1 expression is associated with colorectal tumors. Immunohistochemistry was used to detect ALDH1B1 expression across a commercial colorectal tissue microarray. The signal intensities of the positively stained tissues were expressed using the mean integrated optical density (mean IOD). We also analyzed ALDH1B1 mRNA expression in the Oncomine database. The associations between ALDH1B1 expression and CRC stage and prognosis were then evaluated using the web-based tools, GEPIA and UALCAN. Analysis of the tissue microarray revealed that the expression of ALDH1B1 was significantly higher in colorectal adenomas and colorectal adenocarcinoma (IOD/area values = 0.117±0.070 and 0.168±0.0168, respectively) compared with normal and cancer-adjacent tissues (IOD/area values = 0.051±0.028 and 0.068±0.053). For samples collected in the hospital, ALDH1B1 was highly expressed in the adenoma (IOD/area = 0.103±0.054) and CRC (IOD/area = 0.116±0.059) tissues compared with the cancer-adjacent tissues (IOD/area = 0.066±0.024, p<0.05). The expression of ALDH1B1 in tissues from two resources was not found to be significantly associated with CRC stage. In Oncomine, ALDH1B1 mRNA expression was increased in the colorectal tumor tissues compared with the normal colorectal tissues (p=0.024) and its expression was independent of CRC stage and prognosis (p<0.05). Thus, while the protein and mRNA expression of ALDH1B1 suggests that it is a potential marker of colorectal tumors, its expression is independent of CRC stage and prognosis.
Open Access
Cantharidic acid causes mitochondrial dysfunction via the Nrf2/HO-1/GPX4 pathway to inhibit colorectal cancer progression
(2026) Shulin Dai; Dongyun Zhang; Ting Zhang; Xiaoyu Wang; Yin Li; Wei Huang; Mingliao Niu; Yan Wei; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Background. Cantharidic acid (CA) is a cantharidin analog and has antitumor effects. This study aimed to investigate the antitumor activity of CA against colorectal cancer (CRC) and the underlying mechanisms of this activity. Methods. The impact of CA on the viability of the normal FHC cell line was evaluated by the CCK-8 assay. The malignant behavior of CRC cells was determined using the CCK-8 assay, colony formation assay, Transwell assay, and an LDH commercial kit. The surviving and apoptotic cell numbers were examined via flow cytometry and calcein-AM/PI staining. The ultrastructure of the mitochondria was observed, and the concentration of mtDNA was detected via RT-qPCR. A subcutaneous xenograft tumor model in nude mice was established, and pathological staining was used to assess apoptosis and changes in protein expression. Western blotting was used to evaluate the levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway related proteins and mitochondrial damage-related proteins. Results. CA did not significantly affect FHC viability but was able to reduce CRC cell viability, decrease colony-forming ability, inhibit migration and invasion, and induce apoptosis. CA treatment disrupted mitochondrial morphology and structure and caused a decrease in mitochondrial membrane potential, ATP production, and mtDNA concentration. Treatment with Mito-TEMPO (a mitochondrion-targeted antioxidant) reversed the effects of CA treatment on the above metrics. Furthermore, CA blocked the Nrf2/HO-1/GPX4 pathway, whereas the Nrf2 agonist TBHQ alleviated CA-induced mitochondrial dysfunction. CA treatment decreased the volume and mass of tumor tissue, inhibited cell proliferation, and promoted apoptosis. Notably, CA also led to mitochondrial dysfunction in vivo, which was effectively mitigated by TBHQ. Conclusion. CA blocks the Nrf2/HO-1/GPX4 pathway, causing mitochondrial dysfunction and apoptosis, and thus inhibits the malignant progression of CRC. CA has potential as a therapeutic agent for CRC.
Open Access
Chondroitin polymerizing factor (CHPF) promotes the progression of colorectal cancer through ASB2-mediated ubiquitylation of SMAD9
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhao, Jiang; Tang, Xiaolong; Zhu, Huijun
Chondroitin polymerizing factor (CHPF) has been reported to play a pivotal role in the progression of multiple cancers, however, the relationship between CHPF and colorectal cancer (CRC) progression has not been fully understood. The current study revealed that CHPF expression was upregulated in patients with CRC and correlated with an unfavorable prognosis. Also, CHPF knockdown effectively suppressed the viability and mobility of CRC cells and the growth of xenograft tumors. Additionally, SMAD9 was identified as a downstream target of CHPF. SMAD9 knockdown successfully abrogated the promotion of CHPF overexpression in CRC progression, indicating that CHPF regulated the development of CRC through SMAD9. Mechanistically, SMAD9 is ubiquitinated by ASB2, and the regulatory effect of CHPF on SMAD9 activity was exerted via its mediation of ASB2. Collectively, CHPF functioned as a promising prognostic biomarker and tumor-promoter of CRC by regulating the ASB2-mediated ubiquitination of SMAD9.
Open Access
Circ-CCS regulates oxaliplatin resistance via targeting miR-874-3p/HK2 axis in colorectal cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qiu, Xiaofeng; Xu, Qihua; Liao, Bingling; Hu, Sheng; Zhou, Ying; Zhang, Huijun
Background. Colorectal cancer (CRC) is a malignancy that threatens the patient’s life. Previous reports showed that circular RNAs (circRNAs) can affect CRC development. Herein, we demonstrated the characters of circular RNA copper chaperone for superoxide dismutase (circ-CCS) in CRC tissues and cells. Methods. Circ-CCS, CCS mRNA, microRNA-8743p (miR-874-3p) and hexokinase 2 (HK2) were indicated by qRT-PCR and western blot in CRC. The cell roles were examined. Additionally, the interaction between miR-874-3p and circ-CCS or HK2 was forecasted by the bioinformatics method and assessed by dual-luciferase reporter assay. Finally, the mouse test was implemented to demonstrate the effect of circ-CCS in vivo. Results. Circ-CCS and HK2 were increased, whereas miR-874-3p was diminished in CRC. Circ-CCS lack subdued the IC50 value of oxaliplatin, cell proliferation, migration, invasion and glycolysis metabolism in CRC cells, while it endorsed cell apoptosis. Furthermore, miR-874-3p was validated as having a tumor repressive effect in CRC cells by restraining HK2. The results also showed that HK2 could regulate the development of CRC. In mechanism, circ-CCS targeted miR-874-3p to control HK2. In addition, circ-CCS knock-down also attenuated tumor growth in mice. Conclusion. Circ-CCS expedited CRC through miR874-3p/HK2
Open Access
Claudin-1 role in colon cancer: An update and a review
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Ouban, Abderrahman
Tight junction proteins are essential for sealing the cellular sheets and controlling para-cellular ion flux. Our understanding of the role that tight junction proteins, particularly claudins, play in cellular functions and pathologic conditions is continuously expanding. Particularly, the role of claudin-1 in oncogenesis in multiple locations in the human body is coming to light. This review will shed light on the role of claudin-1 in colon cancer. It will address the mechanisms through which claudin-1 becomes dysregulated in colon cancer. This will provide a platform to address results of claudin-1 expression in the third most common malignant tumour worldwide. Furthermore, it will provide updates about possible use of this biomarker in the surveillance of difficult colon maladies, such as inflammatory bowel disease. The use of claudin-1 as a biomarker of diagnostic and prognostic values will provide Medicine with much needed ammunition in the fight against cancer and will bring about, with added refinements, a new chapter in the era of personalized medicine to tackle this disease and match its destructive course with equally powerful and specifically targeted therapies.
Open Access
Clinical significance of stem cell marker CD133 expression in colorectal cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Bin-Bin; Li, Zhi-juan; Zhang, Feng-Feng; Hou, Hai-Tao; Yu, Jing-Kui; Li, Feng
Objective: CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. Methods: A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. Results: The percentage of CD133- positive (CD133+) tumor cell population ranged between 0.84% and16.75% (mean ratio=7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133+ colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stages, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133+ colorectal cancer HCT116 cellswere sufficient to form tumor xenografts, whereas 1x105 CD133- tumor cells failed to develop tumor xenografts in nude mice. Conclusions: CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.
Open Access
Clinicopathological and molecular features of genome-stable colorectal cancers
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Jin, Lingyan; Jin, Hye Yeong; Kim, Younghoon; Cho, Nam Yun; Bae, Jeong Mo; Kim, Jung Ho; Han, Sae Won; Kim, TaeYou; Kang, Gyeong Hoon
Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined. A total of 437 CRCs were analyzed for copy number variation (CNV) statuses in eight genes (ARID1A, EGFR, FGFR1, KDM5B, MYBL2, MYC, SALL4, and SETDB1) using droplet-digital PCR. CRCs that showed CNV in ≤ one gene and no MSI were defined as GS-like CRCs. Clinicopathological and molecular features of GS-like CRCs were compared with those of CIN-like CRCs. GS-like CRCs comprised 4.6% of CRCs and showed a predilection toward the proximal colon, lower nuclear optical density, KRAS mutation, PIK3CA mutation, and aberrant expression of KRT7. Survival analysis showed no significant difference between the three subgroups. Through our study, the GS-like subtype was found to comprise a minor proportion of CRCs and have proclivity toward a proximal bowel location, hypochromatic tumor nuclei, aberrant KRT7 expression, and a high frequency of KRAS and PIK3CA mutations.
Open Access
Colorectal cancer histopathology image analysis: A comparative study of prognostic values of automatically extracted morphometric nuclear features in multispectral and red-blue-green imagery
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Liu, Wenlou; Qu, Aiping; Yuan, Jingping; Wang, Linwei; Chen, Jiamei; Zhang, Xiuli; Wang, Hongmei; Han, Zhengxiang; Li, Yan
Open Access
Detection and significance of minimal residual disease in colorectal cancer
(Murcia : F. Hernández, 1999) Merrie, A.E.H.; Yun, K.; van Rij, A.M.; McCall, J.L.
Colorectal cancer (CRC) is one of the most common causes of cancer death in the developed world. Although the primary treatment for CRC is surgical, disease relapse due to minimal residual disease (MRD) following apparently curative surgery occurs in up to fifty percent of patients. Most patients who develop overt metastases beyond the regional lymph nodes eventually die of the disease. At present adjuvant chemotherapy is used to improve survival in patients with metastases to regional lymph nodes demonstrated by routine histopathology with no other evidence of spread. The ability to identify metastatic disease at an earlier stage could be of considerable benefit in directing adjuvant therapy to patients at high risk of relapse who are not identified by current methods. Several techniques have been developed for the detection of MRD, including immunohistochemical and molecular methods, however their role in clinical practise is not yet established. The purpose of this paper is to review these techniques and their potential clinical use in the management of CRC.
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Dietary modulation of gut microbiota in patients with colorectal cancer undergoing surgery: a review
(Elsevier, 2022-07-05) Martínez-Montoro, José Ignacio; Martínez-Sánchez, María Antonia; Balaguer-Román, Andrés; Gil-Martínez, José; Mesa-López, María José; Egea Valenzuela, Juan; Ruiz Alcaraz, Antonio José; Queipo-Ortuño, María Isabel; Ferrer Gómez, Mercedes; Fernández García, José Carlos; Ramos-Molina, Bruno; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer death worldwide. Several factors have been postulated to be involved in CRC pathophysiology, including physical inactivity, unhealthy dietary habits, obesity, and the gut microbiota. Emerging data suggest that the microbiome may play a key role in CRC prognosis and derived complications in patients undergoing colorectal surgery. On the other hand, dietary intervention has been demonstrated to be able to induce significant changes in the gut microbiota and related metabolites in different conditions; therefore, the manipulation of gut microbiota through dietary intervention may constitute a useful approach to improve perioperative dysbiosis and post-surgical outcomes in patients with CRC. In this article, we review the role of the gut microbiota in CRC surgery complications and the potential therapeutic modulation of gut microbiome through nutritional intervention in patients with CRC undergoing surgery.
Open Access
Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) He, Shuyan; Lin, Qingfeng; Chen, Jie; Ma, Chenglong; Liu, Zhili; Sun, Yuejun; Mao, Weidong; Shen, Dong; Wang, Jiandong
Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.
Open Access
Expression feature and prognostic function of a novel immune checkpoint Siglec-15 in human colorectal cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Liang, Guodong; Zhou, Linyun; Fan, Yang; Ding, Run; Yang, Junrong; Xu, Li; Zhu, Yidan; Huang, Wen
Background. Sialic acid-bound immuno-globulin lectin 15 (Siglec-15) plays an important role in the development of cancer. However, the association between Siglec-15 expression and clinicopathological characteristics of colorectal cancer (CRC) has not been fully investigated. Methods. In this present study, a number of bioinformatics analyses were performed to provide an overview and detailed characteristics of Siglec-15. Quantitative real-time polymerase chain reaction (qPCR), western blotting and immunohistochemistry analyses were conducted to characterize the expression of Siglec-15 in CRC. Kaplan-Meier survival and Cox regression analyses were performed to identify the prognostic parameters of CRC. Results. The results of bioinformatics analyses revealed the expression characteristics and prognostic roles of Siglec-15 in CRC. The data of qCPR, western blotting, and IHC analyses demonstrated that the expression of Siglec-15 in CRC tissues was significantly higher than that in non-cancerous tissues. Moreover, the expression level of Siglec-15 in CRC was significantly associated with lymph node metastasis (p=0.001), TNM stage (p=0.001), and overall survival (p=0.026). COX multi-factor analysis indicated that Siglec-15 expression (p=0.023) and tumor differentiation (p=0.003) were independent prognostic factors for CRC. Conclusions. Collectively, the data suggested that Siglec-15 expression may serve as a novel prognostic factor and Siglec-15 might be identified as an ideal candidate for immunotherapy in CRC treatment.
Open Access
Gut microbiome modification through dietary intervention in patients with colorectal cancer: protocol for a prospective, interventional, controlled, randomized clinical trial in patients with scheduled surgical intervention for CRC
(MDPI, 2022-06-22) Martínez-Sánchez, María Antonia; Núñez-Sánchez, María Ángeles; Balaguer-Román, Andrés; Oliva-Bolarín, Alba; Pujante-Gilabert, Gabriel; Hernández-Agüera, Quiteria; Mesa-López, María José; Egea Valenzuela, Juan; Queipo-Ortuño, María Isabel; Ruiz Alcaraz, Antonio José; Ferrer Gómez, Mercedes; Gil-Martínez, José; Ramos-Molina, Bruno; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer death worldwide. Several factors have been postulated to be involved in CRC pathophysiology, including heritable and environmental factors, which are the latest to be closely associated with nutritional habits, physical activity, obesity, and the gut microbiota. The latter may also play a key role in CRC prognosis and derived complications in patients undergoing surgery. This is a single-center, open, controlled, randomized clinical trial, in patients with scheduled surgical intervention for CRC. The primary objective is to assess whether a pre-surgical nutritional intervention, based on a high-fiber diet rich in polyunsaturated fatty acids (PUFAs), can reduce disturbances of the gut microbiota composition and, consequently, the rate of post-surgical complications in patients with CRC. Patients will be randomized in a 1:1 ratio after receiving a diagnosis of CRC. In the control arm, patients will receive standard nutritional recommendations, while patients in the intervention arm will be advised to follow a high-fiber diet rich in PUFAs before surgery. Participants will be followed up for one year to evaluate the overall rate of postsurgical complications, recurrences of CRC, response to adjuvant therapy, and overall/disease-free survival.
Open Access
Has_circ_0071803 promotes colorectal cancer progression by regulating miR-330-5p/MAPK signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Huang, Liyong; Dou, Guangjian; Lu, Jiajun; Chen, Zhiheng; Wang, Jiayi
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. A lack of effective targeted therapies against CRC makes the treatment challenging. Here, we report a circular RNA (circRNA), has_circ_0071803, functioning as an oncogene in CRC. Circ_0071803 was upregulated in CRC tissues and cell lines, and its expression levels were inversely correlated with the prognosis and survival rate of patients with CRC. Circ_0071803 knockdown suppressed cell proliferation, migration, and invasion in CRC. Moreover, we found that circ_0071803 sponged miR-330-5p, thereby upregulating mitogen-activated protein kinase 1 (MAPK1) in CRC cells. The suppression of cell activities by circ_0071803 knockdown were rescued by miR-330-5p inhibition or MAPK1 overexpression. Collectively, our findings elucidate that circ_0071803 promotes CRC progression by regulating the miR-330-5p/MAPK1 pathway, providing potential therapeutic targets for designing effective targeted treatments
Open Access
Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Katagiri, Munetoshi; Karasawa, Hideaki; Takagi, Kiyoshi; Nakayama, Shun; Yabuuchi, Shinichi; Fujishima, Fumiyoshi; Naitoh, Takeshi; Watanabe, Mika; Suzuki, Takashi; Unno, Michiaki; Sasano, Hironobu
Background. It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. Patients and methods. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. Results. HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. Conclusion. These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients
Open Access
Histopathological prognostic factors for colorectal liver metastases: A systematic review and meta-analysis of observational studies
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Cavalcante de Oliveira, Cássio Virgílio; Marques Fonseca, Gilton; Pirola Kruger, Jaime Arthur; Sobroza de Mello, Evandro; Ferreira Coelho, Fabricio; Herman, Paulo
Introduction. Resection is the mainstay of treatment for colorectal liver metastases (CRLMs). Many different histopathological factors related to the primary colorectal tumour have been well studied; however, histopathological prognostic factors related to CRLMs are still under evaluation. Objective. To identify histopathological factors related to overall survival (OS) and disease-free survival (DFS) in patients with resected CRLMs. Methods. A systematic review was performed with the following databases up to August 2020: PubMed, EMBASE, Web of Science, SciELO, and LILACS. The GRADE approach was used to rate the overall certainty of evidence by outcome. Results. Thirty-three studies including 4,641 patients were eligible. We found very low certainty evidence that the following histopathological prognostic factors are associated with a statistically significant decrease in OS: presence of portal vein invasion (HR, 410.50 [95% CI, 0.37 to 0.68]; I2=0%), presence of perineural invasion (HR, 0.55 [95% CI, 420.36 to 0.83]; I2=0%), absence of pseudocapsule (HR, 0.41 [CI 95%, 0.29 to 0.57], p<0.00001; I2=0%), presence of satellite nodules (OR, 0.45 [95% CI, 0.26 to 0.80]; I2=0%), and the absence of peritumoural inflammatory infiltrate (OR, 0.20 [95% CI, 0.08 to 0.54]; I2=0%). Outcome data on DFS were scarce, except for tumour borders, which did not present a significant impact, precluding the meta-analysis. Conclusion. Of the histopathological prognostic factors studied, low- to moderate-certainty evidence shows that vascular invasion, perineural invasion, absence of pseudocapsule, presence of satellite nodules, and absence of peritumoral inflammatory infiltrate are associated with shorter overall survival in CRLMs.
Open Access
HM13 is a predictive biomarker of metastasis and neutrophil infiltration in colorectal cancer
(Universidad de Murcia, Histología e Histopatología, 2025) Yanbing Ren; Ying Mao; Xiao Yuan; Biología Celular e Histología
Background. High levels of histo-compatibility minor 13 (HM13) have been related to the progression of several cancers. Here, we investigated the function of HM13 in colorectal cancer (CRC). Methods. HM13 expression, clinicopathology analysis, and its influence on survival were analyzed in multiple public databases (TCGA, TIMER2.0, and GEPIA). HM13 mRNA and protein levels in CRC cells were examined by qRT-PCR and western blot, respectively. CCK-8, Transwell, wound-healing, and adhesion assays were used to measure cell proliferation, migration, invasion, and adhesion in HM13-overexpressed and -silenced cells. The relationship between HM13 expression and neutrophil infiltration was also analyzed. CRC xenograft mouse models were used for in vivo verification of HM13 function. Results. In this study, TCGA dataset analysis revealed that elevated HM13 levels correlated with malignant progression and worse survival outcomes in CRC. Cell migration, proliferation, invasion, and adhesion were suppressed through the knockdown of sh-HM13 and enhanced through HM13 overexpression. Additionally, HM13 expression significantly correlated with the infiltration level of neutrophils in CRC in TCGA and TIMER analyses. HM13 levels were also positively correlated with myeloperoxidase (MPO) levels. In addition, in vivo studies further confirmed that MPO overexpression partially abolished the inhibition of tumor growth by sh-HM13 in CRC. Conclusion. The results suggested that high HM13 expression in CRC could promote tumor growth and metastasis by reducing neutrophil infiltration and may serve as a useful target in the treatment of metastatic CRC.
Open Access
Implication of hepsin from primary tumor in the prognosis of colorectal cancer patients
(MDPI, 2022-06-24) Zaragoza-Huesca, David; Nieto-Olivares, Andrés; García-Molina, Francisco; Ricote, Guillermo; Montenegro, Sofía; Sánchez-Cánovas, Manuel; Garrido-Rodríguez, Pedro; Peñas-Martínez, Julia; Vicente, Vicente; Martínez Díaz, Francisco; Lozano, María Luisa; Carmona-Bayona, Alberto; Martínez-Martínez, Irene; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical histopathological variables by using the chi-square and Kruskal–Wallis tests, Kaplan–Meier and Aalen–Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was asso ciated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical waywith respect to differentiation and invasion processes.