结直肠癌的转移特征：原发肿瘤位置与 KRAS 状态的相互作用。

Metastatic Profile of Colorectal Cancer: Interplay Between Primary Tumor Location and KRAS Status.

机构信息

Department of General Surgery, Singapore General Hospital, Singapore.

Division of Surgical Oncology, National Cancer Centre, Singapore.

出版信息

J Surg Res. 2020 Feb;246:325-334. doi: 10.1016/j.jss.2018.11.025. Epub 2019 Feb 6.

DOI:10.1016/j.jss.2018.11.025

PMID:30737098

Abstract

BACKGROUND

Mutant KRAS tumors are purported to metastasize differently than wild-type KRAS tumors. The biological heterogeneity of tumors from different parts of the colon are also reported to affect metastasis. This study aims to characterize the metastatic profile by evaluating these factors in unison.

METHODS

Retrospective analysis of 899 patients with metastatic colorectal cancers treated from January 2010 to December 2014 was conducted. KRAS mutation status and primary tumors location were correlated with single-site metastasis (liver, lung, and peritoneum) and dual-site metastases (liver-peritoneum, liver-lung, and lung-peritoneum). Patients without KRAS analyses were excluded.

RESULTS

Right-sided tumors had highest frequency of peritoneal metastasis as compared to left-sided or rectal tumors (34.7% versus 15.8% versus 8.8%, P = 0.00) regardless of KRAS status (32.6% versus 38.5%, P = 0.62). Left-sided tumors with wild-type KRAS had greater proportion of liver metastasis (78.6% versus 53.5%, P = 0.00), whereas those with mutant KRAS had greater proportion of lung metastasis (23.3% versus 8.7%, P = 0.02). Rectal tumors with wild-type KRAS tend to spread to the liver (81.4% versus 48.0%, P = 0.00) and not to the peritoneum (2.3% versus 20.0%, P = 0.01). In dual-site metastases, left-sided tumors with wild-type KRAS had more liver-peritoneal metastases (75.0% versus 29.4%, P = 0.00), whereas mutant KRAS had greater lung-liver metastases (64.7% versus 20.8%, P = 0.01). Rectal tumors had the predilection for lung-liver metastases as compared to right-sided and left-sided tumors (92.3% versus 40.0% versus 39.0%, P = 0.00) regardless of KRAS status (100% versus 75%, P = 0.12).

CONCLUSIONS

Our results may streamline surveillance programs based on primary tumor location and KRAS mutational status.

摘要

背景

突变型 KRAS 肿瘤据称比野生型 KRAS 肿瘤具有不同的转移方式。来自结肠不同部位的肿瘤的生物学异质性也被报道会影响转移。本研究旨在通过同时评估这些因素来描述转移特征。

方法

对 2010 年 1 月至 2014 年 12 月期间接受治疗的 899 例转移性结直肠癌患者进行回顾性分析。分析 KRAS 突变状态和原发肿瘤位置与单部位转移（肝、肺和腹膜）和双部位转移（肝-腹膜、肝-肺和肺-腹膜）之间的关系。排除未进行 KRAS 分析的患者。

结果

与左侧或直肠肿瘤相比，右侧肿瘤无论 KRAS 状态如何（32.6% 比 38.5%，P=0.62），腹膜转移的频率更高（34.7% 比 15.8% 比 8.8%，P=0.00）。野生型 KRAS 的左侧肿瘤肝转移比例更高（78.6% 比 53.5%，P=0.00），而突变型 KRAS 的肺转移比例更高（23.3% 比 8.7%，P=0.02）。野生型 KRAS 的直肠肿瘤倾向于转移到肝脏（81.4% 比 48.0%，P=0.00），而不是腹膜（2.3% 比 20.0%，P=0.01）。在双部位转移中，野生型 KRAS 的左侧肿瘤肝-腹膜转移比例更高（75.0% 比 29.4%，P=0.00），而突变型 KRAS 的肺-肝转移比例更高（64.7% 比 20.8%，P=0.01）。与右侧和左侧肿瘤相比，直肠肿瘤更倾向于发生肺-肝转移（92.3% 比 40.0% 比 39.0%，P=0.00），而与 KRAS 状态无关（100% 比 75%，P=0.12）。