Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Okayama 700-8558, Japan.
J Hepatobiliary Pancreat Sci. 2013 Feb;20(2):223-33. doi: 10.1007/s00534-012-0531-9.
The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC).
The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM).
Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes.
The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival.
In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.
对于包括结直肠癌（CRC）在内的恶性肿瘤患者，发现实用的生物标志物对于实现个体化治疗非常重要。
本研究旨在通过分析可切除结直肠肝转移（CRLM）患者来确定可靠的预后生物标志物。
从 126 例接受根治性肝切除的 CRLM 患者的 CRLM 组织中获得基因组 DNA。成功分析了 100 例 CRLM 组织中的 KRAS/BRAF 突变谱和微卫星不稳定性（MSI）状态，并将这些发现与患者的临床结果进行了检查。
100 例 CRLM 患者的队列包括 46 例同步肝转移和 54 例异时性肝转移。5 年总生存率和无病生存率分别为 57.4%和 24.9%。MSI 分析显示，100 例 CRLM 标本中均无 MSI 证据。通过 KRAS/BRAF 突变分析，分析的 CRLM 患者被分为 3 组；KRAS 突变（KRAS-Mt；n = 27）、BRAF 突变（BRAF-Mt；n = 3）和两种基因的野生型（Wild-type；n = 70）。在生存分析中，KRAS-Mt 和 BRAF-Mt 患者的预后均明显差于 Wild-type 患者。此外，尽管 BRAF 突变的人群较小，但该突变对无病生存率有显著的负面影响。
在本研究中，CRLM 患者队列中的所有肿瘤均为非 MSI 肿瘤，提示原发性 CRC 中的 MSI 癌症很少表现出转移潜能。KRAS 和 BRAF 突变被认为是 CRLM 的预后不良因素。遗传信息作为预后标志物具有重要作用，并有助于决定 CRLM 的治疗策略。
