Background: Lung cancer has the highest incidence among solid tumors in men and is the third most common cancer in women. Despite improved understanding of genomic and mutational landscape in non-small cell lung cancer (NSCLC), the five-year survival in these patients has remained stagnant at a dismal 15%. The first line of treatment commonly adapted for NSCLC patients with somatic mutation in EGFR is tyrosine kinase inhibitor gefitinib or erlotinib. EGFR mutant cells seem to be intrinsically sensitive to tyrosine kinase inhibitors; however, the remaining 20-30% patients are resistant to tyrosine kinase inhibitor. Materials and Methods: Here we show, using in vitro normal and NSCLS cell lines, that the lncRNA Prostate androgen-regulated transcript 1 (PART1) is expressed at higher levels in NSCLC cells compared to normal lung epithelial cell line, corroborating two earlier studies. Results: We additionally show that these cells are resistant to erlotinib which is reversed in some, but not all, cell lines following suppression of PART1 expression. The differential response to erlotinib following siRNA-mediated knockdown of PART1 was found to be related to the mutational status of KRAS. Only in cells with wild-type KRAS suppression of PART1 sensitized them to erlotinib. Knockdown of mutant KRAS did not sensitize those cell lines to erlotinib. But knockdown of mutant KRAS along with suppression of PART1 sensitized the cells to treatment with erlotinib. The results from the study reveal a yet undefined and important role of lncRNA PART1 in defining sensitivity to erlotinib. This action is mediated by mutation status of KRAS. Conclusion: Even though preliminary, our results indicate PART1 might be a potential candidate for targeted therapy or used as a predictor of chemosensitivity in patients with NSCLC.
Background: ICIs have remarkably affected the treatment strategies for numerous malignancies, including lung cancer. However, only a fraction of patients experiences durable responses to ICIs, thus there is an urgent need to identify the parameters related to ICIs therapeutic effect. In this study, we investigated nutritional status surrogates and several serum markers to estimate the efficacy of ICIs.Materials and methods: The records of 66 patients with stage Ⅲ/Ⅳ lung cancer who received ICIs were retrospectively analyzed. Features of patients’ clinical pathology, including age, sex, histology, line of treatment, BMI, serum albumin, serum creatinine, and serum inflammatory markers such as LMR and PLR, were examined. Progression-free survival was primary endpoints. Relationships among categorical variables were assessed by the chi-squared test. Survival analysis was performed using Kaplan–Meier method followed by log-rank test. Cox multivariate analysis was performed to analyze the association between each variable and the survival time of patients. Results: The patients with BMI≥25(kg/m2),serum ALB≥37(g/dL),serum creatinine≥61.8(μmol/L), LMR≥2.12 had a significantly prolonged PFS in comparison with BMI<25(kg/m2),ALB<37(g/dL),creatinine<61.8(μmol/L),LMR<2.12 (p < 0.05). No statistically significant difference was detected between patients with PLR<135 and PLR≥135 (p=0.612).The multivariate analysis revealed that ALB≥37(g/dL) and creatinine≥61.8(μmol/L) were associated with prolonged PFS, while statistical significance was not achieved in BMI groups. Conclusions: The current results indicated that high BMI is related to longer PFS in lung cancer patients treated with ICIs, which may be correlated with high levels of serum albumin and creatinine.
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