Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cells. 2019 Jul 4;8(7):678. doi: 10.3390/cells8070678.
Because traditional treatment strategies for advanced gastrointestinal (GI) cancers often have a limited therapeutic effect, immunotherapy could be a viable approach for the therapy of advanced GI cancers, considering the recent success of immunotherapy in treating various refractory malignancies, including the DNA mismatch repair-deficient GI cancers. However, only a subset of cancer patients currently respond to immunotherapy. Thus, it is important to identify useful biomarkers for predicting cancer immunotherapy response. The tumor suppressor gene has a high mutation rate in GI cancers and its deficiency is correlated with the microsatellite instability (MSI) genomic feature of cancer. We investigated the correlation between mutations and tumor immunity using three GI cancer genomics datasets by the bioinformatic approach, and found that diverse antitumor immune signatures were more highly enriched in -mutated GI cancers than in -wildtype GI cancers. The elevated immune activity in -mutated GI cancers was associated with the higher tumor mutation burden and lower tumor aneuploidy level, as well as a higher proportion of MSI cancers in this GI cancer subtype. Moreover, we found that -mutated GI cancers more highly expressed than -wildtype GI cancers. The elevated antitumor immune signatures and expression could contribute to the more active immunotherapeutic responsiveness and better survival prognosis in -mutated GI cancers than in -wildtype GI cancers in the immunotherapy setting, as evidenced in three cancer cohorts receiving immunotherapy. Thus, the mutation could be a useful biomarker for identifying GI cancer patients responsive to immunotherapy.
由于传统的晚期胃肠道（GI）癌症治疗策略通常疗效有限，考虑到免疫疗法在治疗各种难治性恶性肿瘤方面的近期成功，包括 DNA 错配修复缺陷的胃肠道癌症，免疫疗法可能是治疗晚期胃肠道癌症的可行方法。然而，目前只有一部分癌症患者对免疫疗法有反应。因此，确定有用的生物标志物来预测癌症免疫疗法的反应非常重要。肿瘤抑制基因 在胃肠道癌症中具有较高的突变率，其缺失与癌症的微卫星不稳定（MSI）基因组特征相关。我们通过生物信息学方法，使用三个胃肠道癌症基因组数据集研究了 突变与肿瘤免疫之间的相关性，发现与野生型胃肠道癌症相比，不同的抗肿瘤免疫特征在 -突变胃肠道癌症中更为丰富。-突变胃肠道癌症中增强的免疫活性与更高的肿瘤突变负担和更低的肿瘤非整倍体水平以及该胃肠道癌症亚型中更高比例的 MSI 癌症有关。此外，我们发现 -突变胃肠道癌症比野生型胃肠道癌症表达更高的 。在免疫治疗环境中，与野生型胃肠道癌症相比，-突变胃肠道癌症中升高的抗肿瘤免疫特征和 表达可能导致更积极的免疫治疗反应性和更好的生存预后，这在接受免疫治疗的三个癌症队列中得到了证实。因此， 突变可能是识别对免疫疗法有反应的胃肠道癌症患者的有用生物标志物。
