KRAS 突变、微卫星不稳定性和肿瘤侧别对非转移性结肠癌预后的影响。

The impact of KRAS mutation, microsatellite instability, and tumor laterality on the prognosis of nonmetastatic colon cancer.

机构信息

Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.

Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, MN.

出版信息

Surgery. 2022 Mar;171(3):657-665. doi: 10.1016/j.surg.2021.10.043. Epub 2021 Dec 2.

DOI:10.1016/j.surg.2021.10.043

PMID:34865865

Abstract

BACKGROUND

KRAS mutations, microsatellite instability, and tumor location have been found to be significant prognostic factors in colorectal cancer. The interaction between these variables and its effect on overall survival in nonmetastatic colon cancer has not been well elucidated.

METHODS

The National Cancer Database (2010-2016) was queried for patients with stage I-III colon cancer and known microsatellite instability and KRAS status undergoing curative resection.

RESULTS

A total of 5,292 patients were identified: 60.4% had right-sided cancers, 36.4% had KRAS mutations, and 15.6% had microsatellite instability. Right-sided tumors were more likely to have microsatellite instability and KRAS mutations compared to left-sided tumors. On univariable analysis, KRAS mutations and microsatellite instability status were not associated with differences in survival, whereas right-sided cancers had worse overall survival compared to left-sided cancers (hazard ratio 1.32, 95% confidence interval: 1.18-1.47). On multivariable analysis, right-sided location, KRAS mutations, and microsatellite instability were not independent prognostic factors. However, a significant interaction between laterality and KRAS status was observed. In patients with mutated KRAS cancers, left-sided tumors were at increased risk of death compared to right-sided tumors (hazard ratio: 1.30, 95% confidence interval: 1.03-1.63), whereas in patients with wild-type KRAS cancers, left-sided tumors were at decreased risk of death (hazard ratio: 0.81, 95% confidence interval: 0.67-0.97).

CONCLUSION

In patients with stage I-III colon cancer, laterality, KRAS mutation, and microsatellite instability status were not independently prognostic after curative resection. However, the effect of laterality was opposite based on KRAS status, with left-sided (compared to right-sided) tumors associated with worse overall survival in mutated KRAS patients and better overall survival in wild-type KRAS individuals. Laterality itself may not be an independent prognostic factor but a reflection of differing genetic profiles within the colon.

摘要

背景

KRAS 突变、微卫星不稳定性和肿瘤位置已被证实是结直肠癌的重要预后因素。这些变量之间的相互作用及其对非转移性结肠癌总生存的影响尚未得到充分阐明。

方法

从国家癌症数据库（2010-2016 年）中查询接受根治性切除术的 I-III 期结肠癌且微卫星不稳定和 KRAS 状态已知的患者。

结果

共纳入 5292 例患者：60.4%为右侧肿瘤，36.4%有 KRAS 突变，15.6%为微卫星不稳定。与左侧肿瘤相比，右侧肿瘤更可能存在微卫星不稳定和 KRAS 突变。单因素分析显示，KRAS 突变和微卫星不稳定状态与生存差异无关，而右侧肿瘤的总生存较左侧肿瘤差（危险比 1.32，95%置信区间：1.18-1.47）。多因素分析显示，右侧肿瘤位置、KRAS 突变和微卫星不稳定不是独立的预后因素。然而，在侧别和 KRAS 状态之间观察到显著的交互作用。在 KRAS 突变型癌症患者中，与右侧肿瘤相比，左侧肿瘤的死亡风险增加（危险比：1.30，95%置信区间：1.03-1.63），而在 KRAS 野生型癌症患者中，左侧肿瘤的死亡风险降低（危险比：0.81，95%置信区间：0.67-0.97）。

结论

在 I-III 期结肠癌患者中，根治性切除术后，侧别、KRAS 突变和微卫星不稳定状态不是独立的预后因素。然而，基于 KRAS 状态，侧别的作用相反，在 KRAS 突变型患者中，左侧（与右侧相比）肿瘤与总生存较差相关，而在 KRAS 野生型个体中，总生存较好。侧别本身可能不是独立的预后因素，而是结肠内不同遗传特征的反映。