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Updated: Sep 26, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune
Dan Wang1,2, Jiangen Ao1, Youwen Xiong3
1Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
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.
Insights
This study reveals stress granule regulators are altered in non-small cell lung cancer (NSCLC), identifying subtypes linked to survival and drug response. A new stress granule score aids NSCLC prognosis and treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Non-small cell lung cancer (NSCLC) has high incidence and mortality.
- Mechanisms underlying NSCLC progression remain incompletely understood.
Purpose of the Study:
- To investigate the role of Stress Granule Regulators in NSCLC.
- To identify NSCLC subtypes based on these regulators.
- To predict drug response, immune therapy sensitivity, and prognosis.
Main Methods:
- Analysis of TCGA database for NSCLC samples.
- Identification of NSCLC subtypes using expression levels of Stress Granule Regulators.
- Bioinformatics analysis of signaling pathways (cell cycle, mTOR, EGFR, PI3K/Akt, DNA damage repair).
- Prediction of drug response to targeted inhibitors.
- Evaluation of immune therapy response via tumor immune infiltration and TIDE score.
- Construction of a prognostic model (Stress Granule Score).
Main Results:
- Stress Granule Regulators are mutated and dysregulated in NSCLC.
- Three NSCLC subtypes (C1, C2, C3) were identified, with C2 showing better survival.
- Subtypes exhibited differential sensitivity to targeted therapies (e.g., AKT, mTOR, EGFR inhibitors).
- Subtypes C2 and C3 showed potential for improved immune therapy response.
- A prognostic Stress Granule Score (including EIF2S1, CTSG, EIF4G1, IGF2BP1, PABPC1) was developed.
Conclusions:
- Stress granule regulation impacts NSCLC drug response, immune evasion, and patient prognosis.
- This study provides a foundation for novel NSCLC treatment and prognostic strategies.
- The identified NSCLC subtypes offer new avenues for personalized medicine.
