Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma
Abstract Background This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA). Methods and Results The transcriptomic and whole‐exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression‐free survival (PFS), di...
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Wiley
2024-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70135 |
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| author | Baoluhe Zhang Bao Jin Xiang'an Wu Jiali Xing Xiao Liu Xueshuai Wan Haifeng Xu Yiyao Xu Yilei Mao Qian Chen Yating Bai Mei Guan Shunda Du |
| author_facet | Baoluhe Zhang Bao Jin Xiang'an Wu Jiali Xing Xiao Liu Xueshuai Wan Haifeng Xu Yiyao Xu Yilei Mao Qian Chen Yating Bai Mei Guan Shunda Du |
| author_sort | Baoluhe Zhang |
| collection | DOAJ |
| description | Abstract Background This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA). Methods and Results The transcriptomic and whole‐exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression‐free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer‐related transcriptional misregulation, chemokine signaling, and cytokine‐cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer‐related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti‐tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients. Conclusions In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi‐omics analysis. |
| format | Article |
| id | doaj-art-9a79c1b38a4e44b29c807593cf85dcb1 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-9a79c1b38a4e44b29c807593cf85dcb12024-11-26T10:12:30ZengWileyCancer Medicine2045-76342024-08-011316n/an/a10.1002/cam4.70135Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinomaBaoluhe Zhang0Bao Jin1Xiang'an Wu2Jiali Xing3Xiao Liu4Xueshuai Wan5Haifeng Xu6Yiyao Xu7Yilei Mao8Qian Chen9Yating Bai10Mei Guan11Shunda Du12Department of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaThorgene Co., Ltd. Beijing ChinaThorgene Co., Ltd. Beijing ChinaDepartment of Medical Oncology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical college Beijing ChinaDepartment of Liver Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract Background This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA). Methods and Results The transcriptomic and whole‐exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression‐free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer‐related transcriptional misregulation, chemokine signaling, and cytokine‐cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer‐related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti‐tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients. Conclusions In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi‐omics analysis.https://doi.org/10.1002/cam4.70135cholangiocarcinomadifferentiationimmuneintegrated multiomics analysislymphatic node transfer |
| spellingShingle | Baoluhe Zhang Bao Jin Xiang'an Wu Jiali Xing Xiao Liu Xueshuai Wan Haifeng Xu Yiyao Xu Yilei Mao Qian Chen Yating Bai Mei Guan Shunda Du Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma Cancer Medicine cholangiocarcinoma differentiation immune integrated multiomics analysis lymphatic node transfer |
| title | Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| title_full | Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| title_fullStr | Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| title_full_unstemmed | Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| title_short | Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| title_sort | investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma |
| topic | cholangiocarcinoma differentiation immune integrated multiomics analysis lymphatic node transfer |
| url | https://doi.org/10.1002/cam4.70135 |
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