Introduction: PD-1 inhibitors have been approved for the treatment of dMMR patients with metastatic colorectal cancer, but the efficacy of neoadjuvant treatment with PD-1 in dMMR locally advanced rectal cancer (LARC) patients has not yet been defined.Patients and methods: Two patients with LARC received Nivolumab as neoadjuvant treatment in July 2017. Whole-exome sequencing (WES) and multiplex immunofluorescence analysis were performed.Results: Of the two patients, one achieved pathological complete response after six cycles of nivolumab followed by surgery. The other patient was confirmed to be clinical complete response after six cycles of nivolumab. “Watch and wait” strategy was performed for anal preservation. WES showed high tumor mutation burden. Multiplex immunofluorescence analysis showed immune microenvironment alternation between pretreatment specimen and post-treatment specimen.Conclusion: Neoadjuvant nivolumab induced complete response in both of the two patients with LARC. Immunotherapy might be an alternative strategy for neoadjuvant treatment for dMMR/MSI rectal cancer.
Molecular characteristics using gene-expression profiling can undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients. We aimed at developing a genetic signature to improve the prediction of chemosensitivity and prognosis of patients with colorectal cancer (CRC). Patients and Methods: We analyzed microarray data of 32 CRC patients to explore the potential functions and pathways involved in the disease relapse in CRC. Gene expression profiles and clinical follow-up information of GSE39582, GSE17536, and GSE103479 were downloaded from the Gene Expression Omnibus database (GEO) to identify prognostic genes. Eventually, a model of 15-mRNA signature was established, in which its efficacy for predicting chemosensitivity and prognosis was examined. Results: Based on the proposed model of 15-mRNA signature, the test series patients could be classified into high-risk or low-risk subgroup with significantly different overall survival (OS) rate (hazard ratio [HR]=1.48, 95% confidence interval [CI]=1.30-1.70, P≤0.001). The prognostic value of this 15-mRNA signature was confirmed in another validation series. Further analysis revealed that the prognostic value of this signature was independent of the TNM stage and can predict adjuvant chemosensitivity of patients with early-stage CRC. Conclusion: We identified a novel 15-mRNA signature in patients with CRC, which could be clinically helpful in the prognosis evaluation and the process of selection of patients with early-stage CRC for undergoing adjuvant chemotherapy.
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