Browsing by Subject "Lung adenocarcinoma"

Now showing 1 - 8 of 8
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    Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Koike, Chihiro; Okudela, Koji; Matsumura, Mai; Mitsui, Hideaki; Suzuki, Takehisa; Arai, Hiromasa; Kataoka, Toshiaki; Ishikawa, Yoshihiro; Umeda, Shigeaki; Tateishi, Yoko; Ohashi, Kenichi
    The present study aimed to discern the molecular alterations involved in the progression of EGFR-mutated lung adenocarcinoma (LADC). We previously demonstrated that the micropapillary (mPAP) element is the most important histological factor for assessing malignant grades in LADCs. Therefore, mPAP and other elements were separately collected from three cases of EGFR-mutated LADC using laser capture microdissection and subjected to a comprehensive mRNA expression analysis. We focused on DYRK2 in this study because its level showed a substantial increase in EGFR-mutated LADCs with mPAP. We also immunohistochemically examined 130 tumors for the expression of DYRK2. The results confirmed a strong expression of DYRK2 in EGFR-mutated LADC with mPAP. Fluorescent in situ hybridization (FISH) analyses targeting the DYRK2 locus revealed frequent gene amplification in EGFR-mutated LADC, specifically occurring in the high-grade components, like mPAP. In summary, the results of this study suggest that DYRK2 overexpression through gene amplification is one of the molecular mechanisms responsible for promoting the progression of EGFR-mutated LADC.
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    Hsa_circ_0070440 promotes lung adenocarcinoma progression by SLC7A11-mediated-ferroptosis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhao, Yong; Cui, Qichen; Shen, Jian; Shen, Weihong; Weng, Yuan
    Background. Circular RNA (circRNA) has recently emerged as having a key role in cancer initiation and progression. A prior study exhibited that hsa_circ_0070440 (circ_0070440) was significantly upregulated in lung cancer cells, but the role and molecular mechanism of circ_0070440 during lung adenocarcinoma (LUAD) development remain unclear. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR), Reverse transcription-PCR (RTPCR), RNase R digestion, and Nuclear/cytoplasmic fractionation assay were employed to validate circ_0070440. Proliferation, apoptosis, viability, and ferrous iron level were measured by colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), Annexin V-FITC/PI double staining, Cell Counting Kit-8 (CCK-8), and iron assay in LUAD cells. A xenograft mouse model was used for tumor growth in vivo. Western blot (WB) and immunohistochemistry (IHC) assays were utilized to determine the expression of solute carrier family 7 member 11 (SLC7A11), c-myc, and bcl-xL. The interactions between the circ_0070440/SLC7A11 axis and miR-485-5p were verified by RNA pull-down assay and dual-luciferase reporter assay. Results. Circ_0070440 was significantly upregulated in LUAD cells. Knockdown of circ_0070440 inhibited growth and promoted both apoptosis and ferroptosis of LUAD cells. Moreover, our results showed that circ_0070440 contributed to malignant progression and suppressed ferroptosis of LUAD by sponging miR485-5p and upregulating SLC7A11 expression. Furthermore, circ_0070440 and SLC7A11 levels were up-regulated, and the miR-485-5p level was more downregulated in the tumor tissues than in normal tissues of LUAD patients. Conclusion. Circ_0070440 modulated LUAD malignant progression and ferroptosis via targeting SLC7A11, implying a significant role of the circ_0070440/miR-485-5p/SLC7A11 axis in the diagnosis and treatment of LUAD.
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    LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Hong; He, Dongsheng
    Background. Lung adenocarcinoma remains one of the most significant threats to human life as it involves multiple etiologies, including alteration of oncogenes or tumor-inhibitory genes. Long non-coding RNAs (lncRNAs) have been reported to have both cancer promoting and cancer inhibiting effects. In this work, we investigated the function and mechanism of lncRNA LINC01123 in lung adenocarcinoma. Methods. The expression of LINC01123, miR-47665p, and PYCR1 (pyrroline-5-carboxylate reductase 1) mRNA was analyzed by RT-qPCR. The protein expression levels of PYCR1 and the apoptosis-related proteins (Bax and Bcl-2) were determined by western blotting. Cell proliferation and migration were determined by CCK-8 and wound-healing assays, respectively. Tumor growth in nude mice and Ki67 immunohistochemical staining were used to determine the in vivo role of LINC01123. The putative binding relationships miR-4766-5p has with LINC01123 and PYCR1, which had been identified by analysis of public databases, were validated through RIP and dualluciferase reporter assays. Results. LINC01123 and PYCR1 overexpression and miR-4766-5p downregulation were shown to occur in lung adenocarcinoma samples. LINC01123 depletion repressed lung adenocarcinoma cell growth and migration and blocked the development of solid tumors in an animal model. Moreover, LINC01123 bound directly to miR-4766-5p, the downregulation of which attenuated the anticancer effects of LINC01123 depletion in lung adenocarcinoma cells. MiR-4766-5p directly targeted downstream PYCR1 to suppress PYCR1 expression. The repressive effects of PYCR1 knockdown on the migration and proliferation of lung adenocarcinoma cells were also partly abolished by miR-4766-5p downregulation. Conclusion. Downregulation of LINC01123 represses lung adenocarcinoma progression. This suggests that LINC01123 functions as an oncogenic driver in lung adenocarcinoma by controlling the miR4766-5p/PYCR1 axis.
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    MiR-486-5p specifically suppresses SAPCD2 expression, which attenuates the aggressive phenotypes of lung adenocarcinoma cells
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Wei, Desheng
    . Background. MiR-486-5p expression is restrained in lung adenocarcinoma (LUAD). However, much less has been understood on its role in LUAD. We aimed to explore the biofunctions of miR-486-5p in LUAD. Methods. A differential expression analysis based on The Cancer Genome Atlas-LUAD dataset was done to screen the differently expressed miRNAs and mRNAs. MiR-486-5p and SAPCD2 mRNA expression was analyzed by qRT-PCR, and protein level of SAPCD2 was assayed by western blot. Upregulation and downregulation of miR-486-5p or SAPCD2 were achieved by cell transfection. For cell function assays, the proliferation of cancer cells was examined by MTT assay. Cell apoptosis was assessed by flow cytometry and microscopy. Transwell assay was applied to evaluate cell migration and invasion. A dual-luciferase detection was employed to determine the miRNA-mRNA targeting relationship. Results. MiR-486-5p expression was notably reduced in LUAD tissue and cell lines. Upregulating miR-486-5p restrained the anti-apoptotic and proliferative abilities, as well as cell migratory and invasive phenotypes in LUAD cells. SAPCD2 was determined as one target of miR-486-5p. Also, SAPCD2 forced expression was able to attenuate the inhibitory impacts of miR-486-5p on the malignant phenotypes of LUAD cells. Conclusion. MiR-486-5p suppressed cell malignant progression in LUAD by targeting SAPCD2, suggesting that the two may be targets for LUAD treatment.
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    Prognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Serin, Gurdeniz; Savaş, Pınar; İşgör, İrem Şahver; Özdil, Ali; Mızrak, Ali; Veral, Ali; Nart, Deniz
    Background. In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. Methods. A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. Results. At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. Conclusions. The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.
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    Prognostic value of bronchioloalveolar carcinoma component in lung adenocarcinoma
    (Murcia : F. Hernández, 2006) Lin, D.M.; Ma, Y.; Zheng, S.; Liu, X.Y.; Zou, S.M.; Wei, W.Q.
    BAC is a common pattern in conventional lung adenocarcinoma. In the past, however, there were no well-defined criteria for BAC. As a result, it was difficult to evaluate the prognosis on this type of lung adenocarcinoma. Though the 1999 WHO classification of BAC provides a useful framework, it does not provide detailed enough information to predict prognosis in lung adenocarcinomas with BAC feature. The aim of this study was to address the prognostic value of bronchioloalveolar carcinoma (BAC) component in lung adenocarcinoma. Ninety-one consecutive surgically treated patients with adenocarcinoma exhibiting various degrees of BAC features and complete follow-up records were retrospectively studied. According to the percentage of BAC component designed as less than 50%, 50%-79%, 80%-99%, and 100% , tumors were classified as type I, type II, type III, and type IV respectively. The overall 5- year survival rate was 64.84%. Multivariate analysis revealed that the four classified types are independent prognostic factors (P=0.0008), as is tumor stage (P=0.0000). The 5-year survival rates were 39.29%, 58.82%, 81.25%, 85.71% for the four classified types respectively, and were 88.89% for stage I, 46.15% for stage II, and 23.81% for stage III. However, the size of tumor (>2 cm) was significant only in the univariate analysis (P=0.0275). In the patients with tumor size exceeding 2 cm in diameter, the BAC component was also significant to predict prognosis (p=0.0008). In lung adenocarcinoma, the BAC component may prove to be useful to predict the outcome of the patients, and the percentage of BAC pattern and pathological stage appear to be two independent prognostic factors.
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    PTK7 expression is associated with lymph node metastasis, ALK and EGFR mutations in lung adenocarcinomas
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Jiang, Wei; He, Jing; Lv, Bihong; Xi, Xiaoxiang; He, Guangming; He, Jingkang
    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death worldwide. Lung adenocarcinoma is the main tumor type of NSCLC. Recent advances in the molecular characterization and personalized therapies have improved NSCLC patient prognosis. Previous studies showed that protein tyrosine kinase 7 (PTK7) plays an important role in human cancers. However, the role of PTK7 has not been investigated. PTK7 expression was assessed by immunohistochemistry in 95 patients with lung adenocarcinoma. Correlations of PTK7 expression levels with clinicopathological parameters, EGFR mutation and EML4-ALK fusion were examined. Positive PTK7 expression was detected in 47.4% of lung adeno- carcinoma. PTK7 expression was associated with gender (P=0.024), lymph node metastasis (P<0.001), ALK mutation (P=0.050), and EGFR mutations (P=0.014). No significant association was found between PTK7 expression and age (P=0.831), differentiation (P=0.494), adenocarcinoma subtype (P=0.098) and Ki67 (P=0.473). Our data suggest that PTK7 plays an oncogenic role in lung adenocarcinoma and may be a molecular marker for lymph node metastasis.
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    Tropomyosin 2 exerts anti-tumor effects in lung adenocarcinoma and is a novel prognostic biomarker
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Duan, Peng; Cui, Jing; Li, Hongyan; Yuan, Lei
    Background. Tropomyosin 2 (TPM2), a member of the actin filament binding protein family, plays distinct roles in the progression of different cancer types. Until now, there has been no study reporting TPM2 expression nor its function in lung adenocarcinoma (LUAD). Methods. In the present study, we examined the expression profile of TPM2 by immunohistochemistry (IHC). The clinical significance of TPM2 was assessed by univariate and multivariate analyses. Function of TPM2 in LUAD was evaluated by knockdown and overexpression strategies in three LUAD cell lines, followed by proliferation and invasion assays. Xenografts were conducted in nude mice to further validate the tumor-related role of TPM2. Results. Our results showed that TPM2 was downregulated in LUAD specimens and the low expression of TPM2 was associated with poor outcomes of LUAD patients. Overexpressing TPM2 inhibited cell proliferation and invasion of LUAD cell lines, while silencing TPM2 exerted the opposite effects. The effects of TPM2 in LUAD were further confirmed by xenograft assays. Conclusions. Our results indicated that TPM2 exerted an anti-oncogenic role in LUAD via inhibiting tumor progression, thus providing a novel dire