Li Jingjing, Zhang Yiwen, Xu Qi, Wang Gang, Jiang Lai, Wei Qing, Luo Cong, Chen Lei, Ying Jieer
Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang Province, 310022, People's Republic of China.
Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, 310000, People's Republic of China.
Cancer Manag Res. 2021 Mar 30;13:2925-2935. doi: 10.2147/CMAR.S298885. eCollection 2021.
We aimed to assess the differences in gene expression and systemic inflammatory markers in colorectal cancer (CRC) patients with different mismatch repair (MMR) statuses.
Bioinformatics analysis was used to identify the different expression genes in patients with CRC at different MMR statuses. A total of 208 patients with resectable colorectal cancer, including 104 deficient mismatch repair (dMMR) patients and 104 matched proficient mismatch repair (pMMR) patients, were retrospectively analyzed.
Bioinformatics analysis showed that chemokine-mediated signaling pathway and inflammatory responses were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 patients with CRC, those with dMMR frequently had it located on the right side, with more mucinous adenocarcinoma and grade 3 tumors. Patients with dMMR had an earlier American Joint Committee on Cancer (AJCC) stage than pMMR patients. Meanwhile, lymph nodes (LNs) metastasis was more frequently negative in dMMR patients than pMMR patients. Interestingly, patients with CRC with dMMR had more regional lymph nodes removed during surgery, although with less metastatic cancer. Patients with resectable CRC with dMMR were more likely to have higher levels of neutrophil, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and C-reactive protein (CRP). In patients with dMMR, those with higher levels of PLR, MLR, CAR, and co-effect present had shorter overall survival (OS) significantly. It was noteworthy that the prognosis of high levels of systemic inflammatory markers did not predict prolonged OS in patients with pMMR CRC.
dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in patients with CRC with dMMR.
我们旨在评估不同错配修复（MMR）状态的结直肠癌（CRC）患者的基因表达和全身炎症标志物的差异。
采用生物信息学分析来鉴定不同MMR状态的CRC患者中的差异表达基因。对总共208例可切除的结直肠癌患者进行回顾性分析，其中包括104例错配修复缺陷（dMMR）患者和104例匹配的错配修复 proficient（pMMR）患者。
生物信息学分析表明，趋化因子介导的信号通路和炎症反应是dMMR和pMMR CRC患者基因表达的主要差异。在所有208例CRC患者中，dMMR患者的肿瘤常位于右侧，黏液腺癌和3级肿瘤较多。dMMR患者的美国癌症联合委员会（AJCC）分期比pMMR患者早。同时，dMMR患者的淋巴结（LN）转移阴性比pMMR患者更常见。有趣的是，dMMR的CRC患者在手术期间切除的区域淋巴结更多，尽管转移癌较少。可切除的dMMR CRC患者更可能具有较高水平的中性粒细胞、单核细胞、血小板､中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）、单核细胞与淋巴细胞比值（MLR）、C反应蛋白与白蛋白比值（CAR）、格拉斯哥预后评分（GPS）和C反应蛋白（CRP）。在dMMR患者中，PLR、MLR､CAR水平较高且存在协同作用的患者的总生存期（OS）明显较短。值得注意的是，高水平的全身炎症标志物的预后并不能预测pMMR CRC患者的OS延长。
dMMR CRC呈现出全面不同的全身炎症微环境。全身炎症反应可预测dMMR CRC患者的肿瘤学结局。
