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Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation
BACKGROUND: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. METHODS: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655707/ https://www.ncbi.nlm.nih.gov/pubmed/38025711 http://dx.doi.org/10.7717/peerj.16317 |
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author | Wu, Xuan Zhou, Fengrui Cheng, Boran Tong, Gangling Chen, Minhua He, Lirui Li, Zhu Yu, Shaokang Wang, Shubin Lin, Liping |
author_facet | Wu, Xuan Zhou, Fengrui Cheng, Boran Tong, Gangling Chen, Minhua He, Lirui Li, Zhu Yu, Shaokang Wang, Shubin Lin, Liping |
author_sort | Wu, Xuan |
collection | PubMed |
description | BACKGROUND: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. METHODS: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. RESULTS: WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. CONCLUSION: IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC. |
format | Online Article Text |
id | pubmed-10655707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106557072023-11-14 Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation Wu, Xuan Zhou, Fengrui Cheng, Boran Tong, Gangling Chen, Minhua He, Lirui Li, Zhu Yu, Shaokang Wang, Shubin Lin, Liping PeerJ Bioinformatics BACKGROUND: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. METHODS: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. RESULTS: WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. CONCLUSION: IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC. PeerJ Inc. 2023-11-14 /pmc/articles/PMC10655707/ /pubmed/38025711 http://dx.doi.org/10.7717/peerj.16317 Text en ©2023 Wu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Wu, Xuan Zhou, Fengrui Cheng, Boran Tong, Gangling Chen, Minhua He, Lirui Li, Zhu Yu, Shaokang Wang, Shubin Lin, Liping Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title | Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title_full | Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title_fullStr | Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title_full_unstemmed | Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title_short | Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
title_sort | immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655707/ https://www.ncbi.nlm.nih.gov/pubmed/38025711 http://dx.doi.org/10.7717/peerj.16317 |
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