Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer

Abstract

Lung cancer has the world’s second highest cancer incidence and second highest cancer-related mortality rate. However, the mechanism underlying non-small cell lung cancer (NSCLC) remained to be unclear. Overall, this study for the first time revealed Stress Granule Regulators were mutated and dysregulated in NSCLC samples by analyzing TCGA database. Moreover, three subtypes of NSCLC were identified based on the expression levels of Stress Granule Regulators. Patients in cluster 2 showed a higher survival rate than those in clusters 1 and 3. Bioinformatics analysis indicated the cell cycle, mTOR signaling pathway, EGFR signaling, PI3K/Akt signaling and DNA damage repair signaling were significantly related to molecular subtypes. Moreover, we performed a prediction analysis of the response to the inhibitors against the aforementioned signaling. Our results showed patients in C2 NSCLC had the highest sensitivity to MK.2206 (AKT.inhibitor) and Rapamycin (mTOR inhibitor). Patients in C3 NSCLC had the highest sensitivity for Temsirolimus (PI3K/mTOR signaling), BIBW2992 (EGFR signaling), Erlotinib (EGFR signaling), PD.0332991 (CDK4/6 inhibitor), CGP.60474 (CDK inhibitor), and Gefitinib (EGFR signaling). Moreover, our results showed patients in C1 NSCLC had the highest sensitivity to AKT.inhibitor, AZD6482 (PI3K inhibitor). To evaluate the response to immune therapy of different subtypes, we analyzed the tumor immune inflation, immune regulators expression, and TIDE score in different SG related subtypes. These results showed that C2 and C3 may be more sensitive to immune therapy. To better predict the prognosis of NSCLC, we analyzed the correlation between stress granule regulator expression and overall survival time in NSCLC and constructed a Stress Granule Score including EIF2S1, CTSG, EIF4G1, IGF2BP1, PABPC1 to predict the prognosis of NSCLC. Overall, this study for the first time uncovers the effect of stress particles on drug response, immune response, and prognosis, laying a new theoretical foundation for the NSCLC prognosis and treatment.

BTC as a Novel Biomarker Contributing to EMT via the PI3K-AKT Pathway in OSCC

“…Additionally, previous studies have reported that PI3K-AKT signaling pathways could be suppressed after downregulation of EGFR in glioma, pancreatic cancer, and non-small cell lung cancer. (Milton et al, 2020;Han and Wang, 2022;Wang et al, 2022). The level of p-AKT was decreased after treatment of an EGFR antagonist (JMR-132) in ovarian cancers.…”

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway

“…The method we used is similar to that reported in an earlier study we published [ 19 ]. Briefly, the gene expression profiling datasets GSE24988 [ 20 ], GSE113439 [ 21 ] and GSE117261 [ 22 ] are based on GPL6244 ([HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]) were downloaded from the GEO database ( https://www.ncbi.nlm.nih.gov/geo/ ).…”

LncRNAH19 acts as a ceRNA of let-7g to facilitate EndMT in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway

“…The method we used is similar to that reported in an earlier study we published. 19 Brie y, the gene expression pro ling datasets GSE24988 20 , GSE113439 21 and GSE117261 22 are based on GPL6244 ([HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). The GSE24988 dataset contained 62 PH and 22 normal lung tissues.…”