Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
J Cancer Res Clin Oncol. 2020 Jun;146(6):1405-1413. doi: 10.1007/s00432-020-03159-0. Epub 2020 Apr 18.
Major histocompatibility complex (MHC) plays an important role in colorectal cancer (CRC) immunity. However, the function of MHC class I chain-related B (MICB) molecule is not very clear. In this study, we explored the prognostic effect of MICB in colorectal cancer.
From 2008-05 to 2012-11, consecutive CRC patients of Zhongshan Hospital, Fudan University were retrospectively enrolled as primary cohort. The inclusion criteria were as follows: receiving primary radical resection, pathologically confirmed colorectal adenocarcinoma, no treatment before surgery, clinicopathological data available. Another cohort of CRC patients were collected from a public dataset GSE39582 of GEO database from 1987 to 2007 in the same criteria for validation. MICB was detected using immunochemistry and evaluated as prognostic biomarker. The cut-off value of MICB expression was calculated using X-tile software.
Finally, 863 patients were enrolled in the primary cohort, and 556 patients were enrolled in the validation cohort. MICB expression was significantly associated with tumor size and primary histological type in primary cohort, and with primary tumor location and distant metastases in validation cohort. The survival analysis showed that patients with high MICB expression had significantly better overall survival in both primary (P = 0.002) and validation (P = 0.001) cohorts. The multivariate analysis also confirmed that high MICB expression was a significantly independent protective factor for overall survival in both primary (hazard ratio HR = 0.741, 95% CI 0.594-0.924) and validation (HR = 0.699, 95% CI 0.508-0.961) cohorts.
For stage I-IV CRC patients, MICB was confirmed a novel independent prognostic factor. It could help better stratification of CRC prognosis.
主要组织相容性复合体(MHC)在结直肠癌(CRC)免疫中发挥重要作用。然而,MHC Ⅰ类链相关 B(MICB)分子的功能尚不清楚。本研究旨在探讨 MICB 在结直肠癌中的预后作用。
本研究回顾性纳入 2008 年 5 月至 2012 年 11 月复旦大学附属中山医院连续收治的 CRC 患者作为主要队列。纳入标准为:接受原发性根治性切除术、经病理证实为结直肠腺癌、术前未接受任何治疗、具有完整的临床病理资料。另一个 CRC 患者队列来自 GEO 数据库 GSE39582 公共数据集,纳入标准为:2007 年以前,经病理证实为结直肠腺癌,接受原发性根治性切除术,术前未接受任何治疗,具有完整的临床病理资料。采用免疫组化法检测 MICB 表达,并评估其作为预后生物标志物的价值。采用 X-tile 软件计算 MICB 表达的截断值。
最终,主要队列纳入 863 例患者,验证队列纳入 556 例患者。主要队列中,MICB 表达与肿瘤大小和原发组织学类型显著相关,验证队列中与原发肿瘤位置和远处转移显著相关。生存分析显示,高 MICB 表达患者的总生存时间在主要队列(P = 0.002)和验证队列(P = 0.001)中均显著延长。多因素分析也证实,高 MICB 表达是影响主要队列(HR = 0.741,95%CI 0.594-0.924)和验证队列(HR = 0.699,95%CI 0.508-0.961)总生存时间的独立保护因素。
对于Ⅰ-IV 期 CRC 患者,MICB 被证实是一种新的独立预后因素,可以帮助更好地对 CRC 患者进行预后分层。