Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients.

The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients. PD-L1 immunopositivity and mRNA expression were determined by immunohistochemistry using SP263 assay and qRT-PCR, respectively. PD-L1 expression was correlated with various clinicopathological variables, response to therapy, and survival outcomes using appropriate statistical methods. The median age was 60 years (range 33-81 years) with the majority of patients being male (86.5%) and smokers (83%). Histologically, the majority of patients were non-small cell lung cancer (89.4%) and of squamous cell carcinoma histology (64.3%). PD-L1 immunopositivity in tumor cells (tumor proportion score (TPS) ≥ 1%) was detected in 37.6%, while high immunopositivity (TPS ≥ 50%) was detected in 16.8% of lung cancer patients. Almost 76% of lung cancer patients with PD-L1 TPS ≥ 50% belonged to PD-L1 mRNA high-expression group. PD-L1 mRNA expression and immunopositivity did not correlate with response to therapy and survival outcomes. We conclude that PD-L1 immunopositivity and mRNA expression do not seem to serve as a prognostic biomarker for lung cancer patients treated with chemotherapy. More prospective studies should be planned to evaluate the predictive and prognostic relevance of PD-L1 expression in Indian lung cancer patients being treated with immune checkpoint inhibitors.

Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer.

Small cell lung cancer (SCLC), a smoking-related highly aggressive neuroendocrine cancer, is characterized by rapid cell proliferation, early metastatic dissemination, and early relapse due to chemoresistance to first-line platinum-doublet chemotherapy. Genomically, SCLC tumors show nearly universal loss of TP53 and RB1 tumor suppressor genes, while gene expression signature classifies them into 4 distinct subgroups based on the expression patterns of lineage transcription factors - ASCL1/ASH1, NEUROD1, YAP-1, and POU2F3. Due to the lack of targetable molecular alterations and clinically useful diagnostic, prognostic and predictive biomarker, there is insignificant progress in the therapeutic management of SCLC patients. Numerous studies have shown a significant involvement of non-coding RNAs in the regulation of cell proliferation, invasion and migration, apoptosis, metastasis, and chemoresistance in various human cancers. In this review, we comprehensively discuss the role of microRNAs (miRNAs) in regulating the aforementioned biological process in SCLC. For this, we searched the scientific literature and selected studies that have evaluated the role of miRNAs in the disease pathogenesis or as a cancer biomarker in SCLC. Our review suggests that several miRNAs are involved in the pathogenesis of SCLC mainly by regulating cell proliferation, metastasis, and chemoresistance. Few studies have also demonstrated the clinical utility of miRNAs in monitoring response to chemotherapy as well as in predicting survival outcomes. However, more in-depth mechanistic studies utilizing in vivo models and multicentric studies with larger patient cohorts are needed before the applications of miRNAs as therapeutic targets or as biomarkers are translated from the laboratory into clinics.