Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma
Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predi...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.755657/full |
| _version_ | 1798033273248546816 |
|---|---|
| author | Fang Wen Fang Wen Fang Wen Shuai Ruan Shuai Ruan Shuai Ruan Wenjie Huang Wenjie Huang Wenjie Huang Xiaoxue Chen Xiaoxue Chen Xiaoxue Chen Yulan Wang Yulan Wang Yulan Wang Suping Gu Suping Gu Suping Gu Jiatong Liu Jiatong Liu Jiatong Liu Shenlin Liu Shenlin Liu Shenlin Liu Peng Shu Peng Shu Peng Shu |
| author_facet | Fang Wen Fang Wen Fang Wen Shuai Ruan Shuai Ruan Shuai Ruan Wenjie Huang Wenjie Huang Wenjie Huang Xiaoxue Chen Xiaoxue Chen Xiaoxue Chen Yulan Wang Yulan Wang Yulan Wang Suping Gu Suping Gu Suping Gu Jiatong Liu Jiatong Liu Jiatong Liu Shenlin Liu Shenlin Liu Shenlin Liu Peng Shu Peng Shu Peng Shu |
| author_sort | Fang Wen |
| collection | DOAJ |
| description | Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy. |
| first_indexed | 2024-04-11T20:26:37Z |
| format | Article |
| id | doaj.art-f7fabf8f6eef4f95a74dfcc87a59ed5f |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-11T20:26:37Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-f7fabf8f6eef4f95a74dfcc87a59ed5f2022-12-22T04:04:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-11-01810.3389/fmed.2021.755657755657Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell CarcinomaFang Wen0Fang Wen1Fang Wen2Shuai Ruan3Shuai Ruan4Shuai Ruan5Wenjie Huang6Wenjie Huang7Wenjie Huang8Xiaoxue Chen9Xiaoxue Chen10Xiaoxue Chen11Yulan Wang12Yulan Wang13Yulan Wang14Suping Gu15Suping Gu16Suping Gu17Jiatong Liu18Jiatong Liu19Jiatong Liu20Shenlin Liu21Shenlin Liu22Shenlin Liu23Peng Shu24Peng Shu25Peng Shu26Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaCervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.https://www.frontiersin.org/articles/10.3389/fmed.2021.755657/fulltumor mutation burdenimmune infiltrationprognosiscervical squamous cell carcinomaTCGA |
| spellingShingle | Fang Wen Fang Wen Fang Wen Shuai Ruan Shuai Ruan Shuai Ruan Wenjie Huang Wenjie Huang Wenjie Huang Xiaoxue Chen Xiaoxue Chen Xiaoxue Chen Yulan Wang Yulan Wang Yulan Wang Suping Gu Suping Gu Suping Gu Jiatong Liu Jiatong Liu Jiatong Liu Shenlin Liu Shenlin Liu Shenlin Liu Peng Shu Peng Shu Peng Shu Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma Frontiers in Medicine tumor mutation burden immune infiltration prognosis cervical squamous cell carcinoma TCGA |
| title | Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma |
| title_full | Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma |
| title_fullStr | Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma |
| title_full_unstemmed | Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma |
| title_short | Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma |
| title_sort | prognostic value of tumor mutational burden related to immune infiltration in cervical squamous cell carcinoma |
| topic | tumor mutation burden immune infiltration prognosis cervical squamous cell carcinoma TCGA |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.755657/full |
| work_keys_str_mv | AT fangwen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT fangwen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT fangwen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shuairuan prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shuairuan prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shuairuan prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT wenjiehuang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT wenjiehuang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT wenjiehuang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT xiaoxuechen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT xiaoxuechen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT xiaoxuechen prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT yulanwang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT yulanwang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT yulanwang prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT supinggu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT supinggu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT supinggu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT jiatongliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT jiatongliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT jiatongliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shenlinliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shenlinliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT shenlinliu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT pengshu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT pengshu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma AT pengshu prognosticvalueoftumormutationalburdenrelatedtoimmuneinfiltrationincervicalsquamouscellcarcinoma |