KRAS、NRAS、BRAF和PIK3CA基因突变与结直肠癌患者临床病理特征的相关性

郭志琴; 杨宏杰; 袁琳娜; 陈祥义; 邬万新

doi:10.16766/j.cnki.issn.1674-4152.004124

KRAS、NRAS、BRAF和PIK3CA基因突变与结直肠癌患者临床病理特征的相关性

doi: 10.16766/j.cnki.issn.1674-4152.004124

嘉兴大学附属医院病理科，浙江嘉兴 314000

基金项目:

浙江省嘉兴市民生科技创新专项项目 2020AY30008

嘉兴市医学重点支撑学科建设计划项目 2023-ZC-017

浙江省医药卫生科技计划项目 2022KY376

详细信息

通讯作者:
郭志琴，E-mail：guozhq@foxmail.com

中图分类号: R735.3 R730.231
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- 文章访问数: 9
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出版历程
- 收稿日期: 2024-08-05
- 网络出版日期: 2025-10-31

Correlation between KRAS, NRAS, BRAF, and PIK3CA gene mutations and the clinicopathological features of colorectal cancer

Department of Pathology, the Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, China

摘要

摘要: 目的本研究通过分析KRAS、NRAS、BRAF和PIK3CA四种基因突变情况，探讨其与结直肠癌患者临床病理特征的关系，以期为临床个体化治疗提供科学依据。方法回顾性分析嘉兴大学附属医院2019年1月—2022年12月收治的524例结直肠癌患者临床病理资料，运用ARMS-PCR法检测FFPE组织中4种基因突变，并分析其与临床病理特征之间的关系。结果 (1) 本研究4种基因的总突变率为53.4%(280/524)，其中KRAS、NRAS、BRAF和PIK3CA基因突变率分别为46.6%(244/524)、3.2%(17/524)、3.8%(20/524)和2.7%(14/524)。3.6%(19/524)的患者存在共突变。(2)KRAS基因突变主要集中在第2号外显子，突变率为43.1%(226/524)，易发生于女性和黏液腺癌患者(P < 0.05)。(3)NRAS基因第2、3号外显子突变率分别为1.3%(7/524)和1.9%(10/524)，多见于肿瘤长径 < 5 cm的患者(P < 0.05)。(4)BRAF基因突变在肿瘤长径≥5 cm、浸润型、低分化、伴黏液腺癌和脉管侵犯的右半结肠癌患者中更常见(P < 0.05)。(5)伴黏液腺癌患者PIK3CA基因突变率高于未伴黏液腺癌患者[6.3%(5/79) vs. 2.0%(9/445)，χ²=4.785，P=0.029]。结论结直肠癌中KRAS基因突变率高且以第2号外显子突变为主，NRAS、BRAF和PIK3CA基因突变率较低。4种基因突变与不同临床病理特征存在相关性，联合检测有助于结直肠癌患者预后评估和制定个体化精准治疗方案。
- 结直肠肿瘤 /
- 基因突变 /
- KRAS /
- NRAS /
- BRAF /
- PIK3CA
Abstract: Objective To analyze the mutation of KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer, and explore the relationship with clinical pathological characteristics, providing an important reference for clinical individualized treatment. Methods The clinicopathological data of 524 patients in the Affiliated Hospital of Jiaxing University from January 2019 to December 2022 were reviewed. The mutation status of KRAS, NRAS, BRAF, and PIK3CA genes in FFPE tissues was detected by using ARMS-PCR method, and the association between gene mutation status and clinicopathological characteristics was analyzed. Results (1) The total gene mutation rate in this study was 53.4% (280/524), and the mutation rates of KRAS, NRAS, BRAF, and PIK3CA were 46.6% (244/524)、3.2% (17/524)、3.8% (20/524) and 2.7% (14/524), respectively. 3.6% (19/524) of patients had co-mutations in different genes. (2) The mutation of KRAS gene was mainly concentrated in exon 2 (43.1%, 226/524), which was more common in female and patients with mucinous adenocarcinoma (P < 0.05). (3) The mutation rates of NRAS gene in exons 2 and 3 were 1.3% (7/524) and 1.9% (10/524). NRAS gene mutation was prone to occur in patients with tumor diameter﹤5 cm (P < 0.05). (4) BRAF gene mutation was more frequent in patients with tumor diameter ≥5 cm, infiltrative type, poorly-differentiated, mucinous adenocarcinoma and vascular invasion (P < 0.05). Besides, BRAF gene mutation mainly occurred in the right-side colon cancer (P < 0.05). (5) The mutation rate of PIK3CA gene was higher in patients with mucinous adenocarcinoma [6.3% (5/79) vs. 2.0% (9/445), χ²=4.785, P=0.029]. Conclusion KRAS gene mutation rate is higher in colorectal cancer, mainly occurred in exon 2, while NRAS, BRAF, and PIK3CA gene mutations are relatively lower. Mutations in the KRAS, NRAS, BRAF, and PIK3CA genes are associated with different clinicopathological characteristics. Combined detection of the above gene mutation can help to evaluate prognosis and develop individualized precision treatment plan.
- Colorectal neoplasms /
- Gene mutation /
- KRAS /
- NRAS /
- BRAF /
- PIK3CA

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表 1 结直肠癌患者中不同临床病理特征下KRAS、NRAS、BRAF和PIK3CA基因突变的分布情况[例(%)]

Table 1. Distribution of mutations in KRAS, NRAS, BRAF, and PIK3CA genes among colorectal cancer patients with distinct clinicopathological features[cases (%)]

临床病理特征	例数	KRAS基因突变	χ²值	P值	NRAS基因突变	χ²值	P值	BRAF基因突变	χ²值	P值	PIK3CA基因突变	χ²值	P值
性别
男性	331	140(42.3)	6.010	0.014	10(3.0)	0.143	0.706	12(3.6)	0.090	0.765	9(2.7)	0.008	0.930
女性	193	103(53.4)			7(3.6)			8(4.1)			5(2.6)
年龄(岁)
≥60	374	175(46.8)	0.092	0.762	14(3.7)	1.037	0.309	18(4.8)	3.531	0.060	10(2.7)	< 0.001	0.996
＜60	150	68(45.3)			3(2.0)			2(1.3)			4(2.7)
肿瘤长径(cm)
≥5	200	95(47.5)	0.165	0.685	2(1.0)	5.190	0.023	14(7.0)	8.928	0.003	7(3.5)	0.853	0.356
＜5	324	148(45.7)			15(4.6)			6(1.9)			7(2.2)
原发部位
左半结肠	185	76(41.1)	5.682	0.058	9(4.9)	3.644	0.162	6(3.2)	9.336	0.009	2(1.1)	5.116	0.077
右半结肠	162	87(53.7)			2(1.2)			12(7.4)			8(4.9)
直肠	177	80(45.2)			6(3.4)			2(1.1)			4(2.3)
大体类型
隆起型	155	91(58.7)	14.046	0.001	5(3.2)	0.008	0.996	3(1.9)	10.283	0.006	5(3.2)	0.383	0.826
溃疡型	304	128(42.1)			10(3.3)			10(3.3)			7(2.3)
浸润型	65	24(36.9)			2(3.1)			7(10.8)			2(3.1)
分化程度
高分化	3	3(100.0)	3.825	0.148	0	5.554	0.062	0	16.986	< 0.001	0	0.902	0.637
中分化	285	128(44.9)			14(4.9)			2(0.7)			6(2.1)
低分化	236	112(47.5)			3(1.3)			18(7.6)			8(3.4)
伴黏液腺癌
是	79	52(65.8)	14.149	< 0.001	0	3.119	0.077	9(11.4)	14.542	< 0.001	5(6.3)	4.785	0.029
否	445	191(42.9)			17(3.8)			11(2.5)			9(2.0)
脉管侵犯
有	116	48(41.4)	1.495	0.222	4(3.4)	0.020	0.888	9(7.8)	6.306	0.012	2(1.7)	0.514	0.473
无	408	195(47.8)			13(3.2)			11(2.7)			12(2.9)
神经侵犯
有	216	92(42.6)	2.113	0.146	8(3.7)	0.247	0.619	12(5.6)	3.026	0.082	8(3.7)	1.505	0.220
无	308	151(49.0)			9(2.9)			8(2.6)			6(1.9)
伴钙化及血吸虫卵沉着
是	183	96(52.5)	4.187	0.041	6(3.3)	0.001	0.974	7(3.8)	< 0.001	0.994	4(2.2)	0.255	0.613
否	341	147(43.1)			11(3.2)			13(3.8)			10(2.9)

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