Relationship between KRAS, NRAS, BRAF and PIK3CA gene mutations and clinicopathological features in colorectal cancer

doi:10.3877/cma.j.issn.2095-5820.2021.04.005

Abstract

Abstract:

Objective

To study the relationship between KRAS, NRAS, BRAF and PIK3CA mutations and the clinicopathological features in patients with colorectal cancer (CRC).

Methods

The 189 samples of colorectal cancer were collected by surgical excision or biopsy,and DNA were extracted. The mutations of KRAS, NRAS, BRAF and PIK3CA genes were detected by amplification refractory mutation system, and its relationship with clinicopathological features of CRC was analyzed.

Results

The mutations rate of KRAS were 49.7%, in most exon2 mutations; the mutations rate of NRAS were 3.7%; the mutations rate of BRAF were 4.2%; the mutations rate of PIK3CA were 2.6%. There were 5 patients with PIK3CA gene mutations, all of them had KRAS mutations. KRAS mutations were significantly more prevalent in tumors in the proximal colon than in tumors in the distal colon (P=0.048). NRAS mutations rate in patients without nerve bundle invasion were remarkably higher than in patients with nerve bundle invasion (P=0.001). BRAF mutations were significantly more prevalent in tumors in T4 than in tumors in T1-T3 (P=0.029). BRAF mutations were also more common in poorly differentiated tumors than in well and moderately differentiated tumors (P=0.023).

Conclusions

The mutations rate of KRAS gene is high, KRAS, NRAS and BRAF mutations were significantly correlated with the clinicopathological features of CRC.

Key words: Colorectal cancer, Gene, Mutation

Zhijian Lin, Yunjian Xu, Guangming Wen. Relationship between KRAS, NRAS, BRAF and PIK3CA gene mutations and clinicopathological features in colorectal cancer[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2021, 09(04): 217-221.

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References 18

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基因名称	检测区段	突变例数(例)	突变率(%)	合计
	2号外显子	79	41.8	49.7% (94/189)
KARS	3号外显子	6	3.1
	4号外显子	9	4.8

	2号外显子	4	2.1	3.7% (7/189)
NRAS	3号外显子	3	1.6
	4号外显子	0	0.0

BRAF	15号外显子	8	4.2	4.2% (8/189)

PIK3CA	20号外显子	5	2.6	2.6% (5/189)

基因名称	检测区段	突变例数(例)	突变率(%)	合计
	2号外显子	79	41.8	49.7% (94/189)
KARS	3号外显子	6	3.1
	4号外显子	9	4.8

	2号外显子	4	2.1	3.7% (7/189)
NRAS	3号外显子	3	1.6
	4号外显子	0	0.0

BRAF	15号外显子	8	4.2	4.2% (8/189)

PIK3CA	20号外显子	5	2.6	2.6% (5/189)

检测区段	突变类型	例数(例)	合并PIK3CA(例)
2号外显子	G12S，G12D	40	3
2号外显子	G12C，G12R，G12V，G12A，G13C	27	1
2号外显子	G13D	12	1
3号外显子	Q61L，Q61R，Q61H	9	0
4号外显子	K117N，A146T，A146V，A146P	6	0

检测区段	突变类型	例数(例)	合并PIK3CA(例)
2号外显子	G12S，G12D	40	3
2号外显子	G12C，G12R，G12V，G12A，G13C	27	1
2号外显子	G13D	12	1
3号外显子	Q61L，Q61R，Q61H	9	0
4号外显子	K117N，A146T，A146V，A146P	6	0

项目	总例数 n=189	KRAS			NRAS			BRAF			PIK3CA
项目	总例数 n=189	突变	野生	P值	突变	野生	P值	突变	野生	P值	突变	野生	P值
年龄				0.948			1.000			0.968			0.510
＞60岁	105	52	53		4	101		5	100		4	101
≤60岁	84	42	42		3	81		3	81		1	83
性别				0.491			1.000			0.761			0.625
男	116	60	56		4	112		4	112		2	114
女	73	34	39		3	70		4	69		3	70
神经束侵犯				0.714			0.001			0.820			0.585
有	30	14	16		0	30		2	28		1	29
无	159	80	79		7	152		6	153		4	155
脉管癌栓				0.208			0.949			0.871			0.617
有	52	22	30		2	50		2	50		2	50
无	137	72	65		5	132		6	131		3	134
肿瘤大小				0.406			0.783			0.064			0.973
≥5 cm	76	35	41		2	74		6	70		2	74
＜5 cm	113	59	54		5	108		2	111		3	110
临床分期				0.625			0.618			0.851			0.525
Ⅰ期	26	16	10		0	26		0	26		0	26
Ⅱ期	57	27	30		2	55		3	54		2	55
Ⅲ期	61	30	31		4	57		3	58		3	58
Ⅳ期	45	21	24		1	44		2	43		0	45
肿瘤浸润深度				0.505			0.598			0.029			0.849
T1~2	32	18	14		0	32		0	32		0	32
T3	98	50	48		4	94		2	96		3	95
T4	59	26	33		3	56		6	53		2	57
淋巴结转移				0.894			0.417			0.515			0.062
N0	89	45	44		2	87		4	85		1	88
N1	55	28	27		2	53		1	54		4	51
N2	45	21	24		3	42		3	42		0	45
分化程度				0.088			0.549			0.023			1.000
高分化	6	3	3		0	6		0	6		0	6
中分化	169	88	81		6	163		5	164		5	164
低分化	14	3	11		1	13		3	11		0	14
根治程度				0.890			0.350			0.836			0.592
根治	148	74	74		7	141		7	141		5	143
姑息	41	20	21		0	41		1	40		0	41
肿瘤部位				0.048			0.254			0.085			0.166
近端结肠	46	28	18		0	46		3	43		3	43
远端结肠	82	35	47		3	79		5	77		1	81
直肠	61	31	30		4	57		0	61		1	60

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