Dataset Information

MRNAsi-related metabolic risk score model identifies poor prognosis, immunoevasive contexture, and low chemotherapy response in colorectal cancer patients through machine learning.

ABSTRACT: Colorectal cancer (CRC) is one of the most fatal cancers of the digestive system. Although cancer stem cells and metabolic reprogramming have an important effect on tumor progression and drug resistance, their combined effect on CRC prognosis remains unclear. Therefore, we generated a 21-gene mRNA stemness index-related metabolic risk score model, which was examined in The Cancer Genome Atlas and Gene Expression Omnibus databases (1323 patients) and validated using the Zhongshan Hospital cohort (200 patients). The high-risk group showed more immune infiltrations; higher levels of immunosuppressive checkpoints, such as CD274, tumor mutation burden, and resistance to chemotherapeutics; potentially better response to immune therapy; worse prognosis; and advanced stage of tumor node metastasis than the low-risk group. The combination of risk score and clinical characteristics was effective in predicting overall survival. Zhongshan cohort validated that high-risk score group correlated with malignant progression, worse prognosis, inferior adjuvant chemotherapy responsiveness of CRC, and shaped an immunoevasive contexture. This tool may provide a more accurate risk stratification in CRC and screening of patients with CRC responsive to immunotherapy.

SUBMITTER: Weng M

PROVIDER: S-EPMC9445443 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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mRNAsi-related metabolic risk score model identifies poor prognosis, immunoevasive contexture, and low chemotherapy response in colorectal cancer patients through machine learning.

Weng Meilin M Li Ting T Zhao Jing J Guo Miaomiao M Zhao Wenling W Gu Wenchao W Sun Caihong C Yue Ying Y Zhong Ziwen Z Nan Ke K Liao Qingwu Q Sun Minli M Zhou Di D Miao Changhong C

Frontiers in immunology 20220823

Colorectal cancer (CRC) is one of the most fatal cancers of the digestive system. Although cancer stem cells and metabolic reprogramming have an important effect on tumor progression and drug resistance, their combined effect on CRC prognosis remains unclear. Therefore, we generated a 21-gene mRNA stemness index-related metabolic risk score model, which was examined in The Cancer Genome Atlas and Gene Expression Omnibus databases (1323 patients) and validated using the Zhongshan Hospital cohort ...[more]

PMID: 36081499

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Project description:BackgroundThe role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC.MethodsThis study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.ResultsWe observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.ConclusionCD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Dataset Information

MRNAsi-related metabolic risk score model identifies poor prognosis, immunoevasive contexture, and low chemotherapy response in colorectal cancer patients through machine learning.

Publications

mRNAsi-related metabolic risk score model identifies poor prognosis, immunoevasive contexture, and low chemotherapy response in colorectal cancer patients through machine learning.

Similar Datasets

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