Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer
BackgroundThe current tumor-node-metastasis (TNM) staging system is insufficient for predicting the efficacy of chemotherapy in patients with gastric cancer (GC). This study aimed to analyze the association between the focal adhesion pathway and therapeutic efficacy of chemotherapy in patients with...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.808817/full |
| _version_ | 1818476078680768512 |
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| author | Xiaohuan Tang Xiaolong Wu Ting Guo Fangzhou Jia Ying Hu Xiaofang Xing Xiangyu Gao Ziyu Li |
| author_facet | Xiaohuan Tang Xiaolong Wu Ting Guo Fangzhou Jia Ying Hu Xiaofang Xing Xiangyu Gao Ziyu Li |
| author_sort | Xiaohuan Tang |
| collection | DOAJ |
| description | BackgroundThe current tumor-node-metastasis (TNM) staging system is insufficient for predicting the efficacy of chemotherapy in patients with gastric cancer (GC). This study aimed to analyze the association between the focal adhesion pathway and therapeutic efficacy of chemotherapy in patients with GC.MethodsRNA sequencing was performed on 33 clinical samples from patients who responded or did not respond to treatment prior to neoadjuvant chemotherapy. The validation sets containing 696 GC patients with RNA data from three cohorts (PKUCH, TCGA, and GSE14210) were analyzed. A series of machine learning and bioinformatics approaches was combined to build a focal adhesion-related signature model to predict the treatment efficacy and prognosis of patients with GC.ResultsAmong the various signaling pathways associated with cancer, focal adhesion was identified as a risk factor related to the treatment efficacy of chemotherapy and prognosis in patients with GC. The focal adhesion-related gene model (FAscore) discriminated patients with a high FAscore who are insensitive to neoadjuvant chemotherapy in our training cohort, and the predicted value was further verified in the GSE14210 cohort. Survival analysis also demonstrated that patients with high FAscores had a relatively shorter survival compared to those with low FAscores. In addition, we found that the levels of tumor mutation burden (TMB) and microsatellite instability (MSI) increased with an increase in FAscore, and the tumor microenvironment (TME) also shifted to a pro-tumor immune microenvironment.ConclusionThe FAscore model can be used to predict the treatment efficacy of chemotherapy and select appropriate treatment strategies for patients with GC. |
| first_indexed | 2024-12-10T09:20:55Z |
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| id | doaj.art-185eb0d7fa4c447981e809d27c47b521 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T09:20:55Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-185eb0d7fa4c447981e809d27c47b5212022-12-22T01:54:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.808817808817Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric CancerXiaohuan Tang0Xiaolong Wu1Ting Guo2Fangzhou Jia3Ying Hu4Xiaofang Xing5Xiangyu Gao6Ziyu Li7Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaBiological Sample Bank, Peking University Cancer Hospital & Institute, Beijing, ChinaBiological Sample Bank, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, ChinaBackgroundThe current tumor-node-metastasis (TNM) staging system is insufficient for predicting the efficacy of chemotherapy in patients with gastric cancer (GC). This study aimed to analyze the association between the focal adhesion pathway and therapeutic efficacy of chemotherapy in patients with GC.MethodsRNA sequencing was performed on 33 clinical samples from patients who responded or did not respond to treatment prior to neoadjuvant chemotherapy. The validation sets containing 696 GC patients with RNA data from three cohorts (PKUCH, TCGA, and GSE14210) were analyzed. A series of machine learning and bioinformatics approaches was combined to build a focal adhesion-related signature model to predict the treatment efficacy and prognosis of patients with GC.ResultsAmong the various signaling pathways associated with cancer, focal adhesion was identified as a risk factor related to the treatment efficacy of chemotherapy and prognosis in patients with GC. The focal adhesion-related gene model (FAscore) discriminated patients with a high FAscore who are insensitive to neoadjuvant chemotherapy in our training cohort, and the predicted value was further verified in the GSE14210 cohort. Survival analysis also demonstrated that patients with high FAscores had a relatively shorter survival compared to those with low FAscores. In addition, we found that the levels of tumor mutation burden (TMB) and microsatellite instability (MSI) increased with an increase in FAscore, and the tumor microenvironment (TME) also shifted to a pro-tumor immune microenvironment.ConclusionThe FAscore model can be used to predict the treatment efficacy of chemotherapy and select appropriate treatment strategies for patients with GC.https://www.frontiersin.org/articles/10.3389/fonc.2022.808817/fullgastric cancerfocal adhesiontreatment efficacyprognosistumor microenvironment |
| spellingShingle | Xiaohuan Tang Xiaolong Wu Ting Guo Fangzhou Jia Ying Hu Xiaofang Xing Xiangyu Gao Ziyu Li Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer Frontiers in Oncology gastric cancer focal adhesion treatment efficacy prognosis tumor microenvironment |
| title | Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer |
| title_full | Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer |
| title_fullStr | Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer |
| title_full_unstemmed | Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer |
| title_short | Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer |
| title_sort | focal adhesion related signatures predict the treatment efficacy of chemotherapy and prognosis in patients with gastric cancer |
| topic | gastric cancer focal adhesion treatment efficacy prognosis tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.808817/full |
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