Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer
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 dysreg...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.868918/full |
| _version_ | 1811260632014520320 |
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| author | Dan Wang Dan Wang Jiangen Ao Youwen Xiong Xinyi Zhang Weifang Zhang |
| author_facet | Dan Wang Dan Wang Jiangen Ao Youwen Xiong Xinyi Zhang Weifang Zhang |
| author_sort | Dan Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:50:15Z |
| format | Article |
| id | doaj.art-9905280a3d5644ee8aa35c4922bc8569 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T18:50:15Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-9905280a3d5644ee8aa35c4922bc85692022-12-22T03:20:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-03-011010.3389/fcell.2022.868918868918Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung CancerDan Wang0Dan Wang1Jiangen Ao2Youwen Xiong3Xinyi Zhang4Weifang Zhang5Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaState Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Testing, Jiangxi Center of Medical Device Testing, Nanchang, ChinaDepartment of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaLung 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.868918/fullnon-small cell lung cancerstress granulemolecular subtypesdrug responseimmune responseprognosis |
| spellingShingle | Dan Wang Dan Wang Jiangen Ao Youwen Xiong Xinyi Zhang Weifang Zhang Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer Frontiers in Cell and Developmental Biology non-small cell lung cancer stress granule molecular subtypes drug response immune response prognosis |
| title | Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer |
| title_full | Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer |
| title_fullStr | Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer |
| title_full_unstemmed | Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer |
| title_short | Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer |
| title_sort | systematic analysis of stress granule regulators associated molecular subtypes predicts drug response immune response and prognosis in non small cell lung cancer |
| topic | non-small cell lung cancer stress granule molecular subtypes drug response immune response prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.868918/full |
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