Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients
BackgroundNumerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).MethodsBased on R software, we performed the ssGSEA, differential expression analysis, Kaplan-M...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1064704/full |
| _version_ | 1797945437620011008 |
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| author | Taohua Yue Yunlong Cai Jing Zhu Yucun Liu Shanwen Chen Pengyuan Wang Long Rong |
| author_facet | Taohua Yue Yunlong Cai Jing Zhu Yucun Liu Shanwen Chen Pengyuan Wang Long Rong |
| author_sort | Taohua Yue |
| collection | DOAJ |
| description | BackgroundNumerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).MethodsBased on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments.ResultsUsing autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A.ConclusionAutophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator. |
| first_indexed | 2024-04-10T20:56:12Z |
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| id | doaj.art-f3a627a769ee4747aef0cd4cf1e9f55b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:56:12Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f3a627a769ee4747aef0cd4cf1e9f55b2023-01-23T06:42:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10647041064704Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patientsTaohua Yue0Yunlong Cai1Jing Zhu2Yucun Liu3Shanwen Chen4Pengyuan Wang5Long Rong6Department of Endoscopy Center, Peking University First Hospital, Peking University, Beijing, ChinaDepartment of Endoscopy Center, Peking University First Hospital, Peking University, Beijing, ChinaDivision of General Surgery, Peking University First Hospital, Peking University, Beijing, ChinaDivision of General Surgery, Peking University First Hospital, Peking University, Beijing, ChinaDivision of General Surgery, Peking University First Hospital, Peking University, Beijing, ChinaDivision of General Surgery, Peking University First Hospital, Peking University, Beijing, ChinaDepartment of Endoscopy Center, Peking University First Hospital, Peking University, Beijing, ChinaBackgroundNumerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).MethodsBased on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments.ResultsUsing autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A.ConclusionAutophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1064704/fullcolon adenocarcinoma (COAD)autophagyIFNgprognosisimmunotherapycisplatin |
| spellingShingle | Taohua Yue Yunlong Cai Jing Zhu Yucun Liu Shanwen Chen Pengyuan Wang Long Rong Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients Frontiers in Immunology colon adenocarcinoma (COAD) autophagy IFNg prognosis immunotherapy cisplatin |
| title | Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients |
| title_full | Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients |
| title_fullStr | Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients |
| title_full_unstemmed | Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients |
| title_short | Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients |
| title_sort | autophagy related ifng is a prognostic and immunochemotherapeutic biomarker of coad patients |
| topic | colon adenocarcinoma (COAD) autophagy IFNg prognosis immunotherapy cisplatin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1064704/full |
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