Lung cancer, the most common malignancy, is still the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80 % of all lung cancers. Recent studies showed Cathepsin L (CTSL) is overexpressed in various cancerous tissues; however, the association between CTSL expression and EGFR-TKI resistance remains unknown. In this study, we investigated the expression of CTSL in lung cancer specimens and matched normal tissues by quantitative real-time PCR and IHC. The functional role of CTSL in resistant PC-9/GR cell line was investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that the level of CTSL expression was higher in NSCLC tissues compared with matched normal adjacent tissue samples, and CTSL was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking-down of CTSL in PC-9/GR cells could decrease cell proliferation and potentiate apoptosis induced by gefitinib, suggesting CTSL may contribute to gefitinib resistance in NSCLC. CTSL might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.
few large-scale studies revealed the clear correlation between age, tumor nodes metastases (TNM) staging and morbidity in this rare population. Method: The age of ALK-positive lung cancer at initial diagnosis were compared between various TNM stages. Clinical characteristics, morbidity and prognosis were analyzed stratified by different age groups. Results: Of 411 patients, the younger group showed more frequent T3/4 stage (P ¼ 0.014), more frequent lymph nodes metastasis (P ¼ 0.011) and more frequent distant metastasis (P ¼ 0.015). Across the entire patient cohort, the median age was 51 years, which decreased steadily with clinical stages (stage I/II vs. III vs. IV, 55 vs. 52 vs. 49 years). There was significant inverse correlation between age and clinical stages (P < 0.001). These laws also existed at various T, N, M categories. What was more, morbidity of ALK rearrangement manifested a steady downward trend with older age groups (40 vs. 40-49 vs. 50-59 vs. 60 years: 18.8% vs. 11.6% vs. 5.0% vs. 2.2%). Surprisingly, ALK-positive patients with stage IIIb-IV disease had much higher incidence than the patients with stage I-IIIa disease (6.1% vs. 3.4%, P < 0.001). Finally, the ALK-positive patients aged younger showed poorer outcomes compared with the older group. Conclusion: TNM staging exhibited a significant inverse correlation with age in ALK-positive lung cancer. More unique therapeutic and research strategies should be required in these patients of young age.
selected due to their paired nature, complete with both LUAD and nonmalignant lung profiles (TCGA n¼108, BCCA n¼72). LncRNAs were filtered based on positional overlap within pseudogene loci, and a Wilcoxon sign-rank test was run to identify lncRNAs with significantly altered expression between paired tumor and normal tissues (FDR p<0.05). To identify lncRNAs that likely regulate protein-coding parent gene expression in trans, tumors were ranked by lncRNA expression, and protein-coding parent gene expression of top and bottom ranked tertiles was compared by Mann Whitney U-test (p<0.05). Survival analysis was performed using a Cox proportional hazard model. Result: Our analysis has identified 129 lncRNAs expressed from pseudogene loci that were significantly deregulated in LUAD in both datasets. Remarkably, many of these deregulated lncRNAs (i) were expressed from the loci of pseudogenes related to known cancer genes, (ii) had expression that significantly correlated with protein-coding parent gene expression, and (iii) protein-coding parent gene expression was significantly associated with survival. For example, RP11-182J1.1 is a lncRNA expressed from a pseudogene to EGLN1, a previously described cancer gene involved in regulation of tumor hypoxia. RP11-182J1.1 was underexpressed in LUAD and significantly positively correlated with EGLN1 expression. In addition, EGLN1 was significantly associated with patient survival (p¼1.2e-08) emphasizing the clinical potential of these lncRNAs. Conclusion: This work uncovers evidence to suggest the lncRNA-pseudogene-protein-coding gene axis is a prominent mechanism of cancer gene regulation. Further characterization of this understudied gene regulatory mechanism could lead to novel therapies that silence oncogenes or reactivate tumor suppressor genes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.