Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy

Lin, Yan; Zhang, Yumei; Wu, Guobin; Ye, Jiazhou; Luo, Shanshan; He, Xu; Luo, Min; Xie, Min; Zhang, Jinyan; Li, Qian; Huang, Yu; Liao, Sina; Li, Yongqiang; Liang, Rong

doi:10.3389/fphar.2022.920939

Cited by 2 publications

(1 citation statement)

References 51 publications

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“…COAD patients show high morbidity and mortality rates because of metastasis, cancer recurrence, and chemotherapy resistance [22]. An increasing number of studies have suggested that a typical characteristic of malignancy is abnormal one-carbon metabolism, which play key role in protein synthesis, especially, methionine serves as the primary methyl source for DNA, protein, and lipid methylation via S-adenosyl-methionine (SAM) [23].…”

Section: Discussionmentioning

confidence: 99%

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

Wang,

Zhi-Min,

Wang

2023

Preprint

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Background: To study one-carbon metabolism-related genes and their association with Colon adenocarcinoma (COAD) prognosis, immune cell infiltration, and search for new therapeutic targets and drugs. Methods: The univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression for COAD prognosis from The Cancer Genome Atlas (TCGA), and the prognostic efficacy of the one carbon unit and amino acid -related gene signature was assessed using Kaplan–Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The co-expression of one-carbon metabolism -related genes with miRNAs or circRNAs and M6A-related genes in COAD was analyzed. Using CIBERSORT, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. Potential small-molecule agents were identified using the GDSC database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT–PCR) assays were conducted. Results: We identified three one-carbon metabolism -related genes (AHCY, BHMT, SLC38A2) for the prognostic signature of overall survival (OS) for COAD. The binding information between metabolism-related genes, target miRNAs and circRNAs indicated that miR-140-5p and miR-195-5p/ hsa_circ_0071989had a good prediction. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. AHCY and BHMT, SLC38A2 mRNA expression was increased in HCT116 cells, whereas miRNA (miR-140-5p and miR-195-5p) expression was decreased in HCT116 cells. Conclusion:In summary, we identified and developed a one-carbon metabolism -related gene signature with significant prognostic value of COAD, and AHCY, BHMT, SLC38A2 were positively regulated by the m6A genes in COAD samples. The combination TGX221 with cyclopamin significantly decreased AHCY, BHMT and SLC38A2 via upregulating miR-140-5p and miR-195-5p in HCT116 cells, which benefits COAD patients by informing more precise and effective treatment decisions.

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Section: Discussionmentioning

confidence: 99%

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

Wang,

Zhi-Min,

Wang

2023

Preprint

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Immunogenic chemotherapy: great potential for improving response rates

Huang,

Ren,

Yang

et al. 2023

Front. Oncol.

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The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by inducing immunogenic cell death and durably eradicate tumors. This suggests that immunogenic chemotherapy holds great potential for improving response rates. However, chemotherapy in practice has only had limited success in inducing long-term survival or cure of cancers when used either alone or in combination with immunotherapy. We think that this is because the importance of dose, schedule, and tumor model dependence of chemotherapy-activated anti-tumor immunity is under-appreciated. Here, we review immune modulation function of representative chemotherapy agents and propose a model of immunogenic chemotherapy-induced long-lasting responses that rely on synergetic interaction between killing tumor cells and inducing anti-tumor immunity. We comb through several chemotherapy treatment schedules, and identify the needs for chemotherapy dose and schedule optimization and combination therapy with immunotherapy when chemotherapy dosage or immune responsiveness is too low. We further review tumor cell intrinsic factors that affect the optimal chemotherapy dose and schedule. Lastly, we review the biomarkers indicating responsiveness to chemotherapy and/or immunotherapy treatments. A deep understanding of how chemotherapy activates anti-tumor immunity and how to monitor its responsiveness can lead to the development of more effective chemotherapy or chemo-immunotherapy, thereby improving the efficacy of cancer treatment.

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Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy

Cited by 2 publications

References 51 publications

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

Identification of One-carbon metabolism-related gene signature and Analysis of the role of m6A and miRNAs/circRNAs for colon adenocarcinoma

Immunogenic chemotherapy: great potential for improving response rates

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