Effect of KRAS gene mutation on clinical prognosis of resectable pancreatic cancer

doi:10.3877/cma.j.issn.2095-3232.2025.03.019

Abstract

Abstract:

Objective

To evaluate the effect of Kirsten rat sarcoma virus （KRAS） gene mutation on clinical prognosis of resectable pancreatic cancer.

Methods

Clinical data of 96 patients with pancreatic cancer admitted to People’s Hospital of Xinjiang Uygur Autonomous Region from January 2022 to May 2023 were retrospectively analyzed. Among them， 62 patients were male and 34 female， aged from 54 to 76 years，with a median age of 70 years. The informed consents of all patients and families were obtained and the local ethical committee approval was received.Preoperative CA19-9 level was 29-4 500 kU/L. 50 cases were diagnosed with pancreatic head cancer and 46 cases of pancreatic body and tail cancer. All patients received adjuvant chemotherapy after surgery. The KRAS gene mutation in the patients was observed. Prognostic factors of pancreatic cancer patients were identified by Cox proportional hazard model. Survival analysis was performed by Kaplan-Meier method and Log-rank test.

Results

The mutation rate of KRAS gene in pancreatic cancer patients was 71%（68/96）. The detection of KRAS mutation sites showed that the four most frequent mutation sites of KRAS gene were p.G12D（n=33）， p.G12V（n=19）， p.G12R （n=7） and p.Q61H （n=5）， and 4 cases were other sites. Among KRAS mutation sites， p.G12D and p.G12V were the dominant sites. Multivariate Cox regression analysis demonstrated that KRAS gene mutation， tumor differentiation and lymphatic vessel invasion were the independent risk factors for clinical prognosis of pancreatic cancer （HR=2.424， 2.314，1.782； all P＜0.05）. The follow-up time was 6-36 months， with a median of 21 months. The 1-year survival rate of pancreatic cancer patients with KRAS gene mutation after operation was 94.1%， and 96.4% for those without KRAS gene mutation， and the difference was statistically significant （χ²=23.400， P＜0.05）. However，the difference was not statistically significant between the KRAS p.G12D and non-p.G12D mutation subgroups（χ²=0.055， P＞0.05）.

Conclusions

KRAS gene mutation is an independent risk factor for the clinical prognosis of patients with resectable pancreatic cancer. Patients with KRAS gene mutation have poor prognosis. However，no significant difference is noted in clinical prognosis among patients with different KRAS mutation sites.

Key words: Kirsten rat sarcoma viral oncogene homolog (KRAS), Mutation, Pancreatic cancer, Survival prognosis, Recurrence

Bingli Zheng, Jie Peng, Yuan Meng. Effect of KRAS gene mutation on clinical prognosis of resectable pancreatic cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(03): 456-462.

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References 30

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因素	未复发或未死亡	复发或死亡	χ ²值	P值
男性	47	15	0.740	0.389
年龄＞70岁	31	16	2.258	0.132
术前CA19-9＞150 kU/L	28	17	4.905	0.026
胰头癌	36	14	0.044	0.833
分化程度（好/中/差）	32/28/10	3/8/15	12.207	＜0.001
病理T分期（T1/ T2/ T3～T4）	27/34/9	6/8/12	5.548	0.018
病理N分期（N0/N1/ N2）	25/39/6	7/8/11	5.263	0.021
淋巴血管侵犯	32	23	14.158	＜0.001
神经侵犯	29	16	3.078	0.079
R0切除	39	11	1.365	0.242
KRAS基因突变及亚型	43	25	11.065	＜0.001
p.G12D	23	10	0.264	0.607
p.G12V	12	7	1.423	0.285
p.G12R	3	4	2.008	0.156
p.Q61H	3	2	0.023	0.880
其他	2	2	0.229	0.0632

因素	未复发或未死亡	复发或死亡	χ ²值	P值
男性	47	15	0.740	0.389
年龄＞70岁	31	16	2.258	0.132
术前CA19-9＞150 kU/L	28	17	4.905	0.026
胰头癌	36	14	0.044	0.833
分化程度（好/中/差）	32/28/10	3/8/15	12.207	＜0.001
病理T分期（T1/ T2/ T3～T4）	27/34/9	6/8/12	5.548	0.018
病理N分期（N0/N1/ N2）	25/39/6	7/8/11	5.263	0.021
淋巴血管侵犯	32	23	14.158	＜0.001
神经侵犯	29	16	3.078	0.079
R0切除	39	11	1.365	0.242
KRAS基因突变及亚型	43	25	11.065	＜0.001
p.G12D	23	10	0.264	0.607
p.G12V	12	7	1.423	0.285
p.G12R	3	4	2.008	0.156
p.Q61H	3	2	0.023	0.880
其他	2	2	0.229	0.0632

变量	b	SE（b）	HR	95%CI	Waldχ ²	P值
术前CA19-9	0.501	0.350	1.651	0.830～3.284	2.041	0.153
肿瘤分化程度	0.885	0.337	2.424	1.252～4.693	6.899	0.008
病理T分期	0.319	0.297	1.377	0.769～2.465	1.158	0.281
病理N分期	0.421	0.383	1.525	0.719～3.234	1.210	0.271
淋巴血管侵犯	0.838	0.326	2.314	1.220～4.389	6.599	0.010
KRAS基因突变	0.577	0.204	1.782	1.194～2.659	7.996	0.004

变量	b	SE（b）	HR	95%CI	Waldχ ²	P值
术前CA19-9	0.501	0.350	1.651	0.830～3.284	2.041	0.153
肿瘤分化程度	0.885	0.337	2.424	1.252～4.693	6.899	0.008
病理T分期	0.319	0.297	1.377	0.769～2.465	1.158	0.281
病理N分期	0.421	0.383	1.525	0.719～3.234	1.210	0.271
淋巴血管侵犯	0.838	0.326	2.314	1.220～4.389	6.599	0.010
KRAS基因突变	0.577	0.204	1.782	1.194～2.659	7.996	0.004

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