Meta-analysis of the effect of BRAF gene mutation on the prognosis of colorectal cancer patients with liver metastases after hepatectomy

doi:10.3969/j.issn.1674-8115.2021.06.014

Abstract

Abstract: Objective

·To assess the impact of BRAF gene mutation on the prognosis of colorectal cancer liver metastasis (CRLM) patients after hepatectomy.

Methods

·The clinical research was obtained from PubMed from January 2010 to June 2020. Retrieval method was as follows: "BRAF" and ("colon" or "colorectal" or "rectal" or "rectum") and ("metastasis" or "metastatic" or "metastases" or "mets" or "metastasectomy") and ("hepatic" or "liver"). The articles were screened according to inclusion and exclusion criterias, and the quality evaluation and data extraction were carried out. The RevMan 5.4 software was used for meta-analysis. The main outcome index was overall survival (OS), and the secondary outcome index was disease-free survival (DFS).

Results

·Finally, seven studies containing 2 722 patients were included in the meta-analysis. The mutation rate of BRAF was 5.77%. Seven studies reported CRLM patients' OS after hepatic resection through stratified analysis by BRAF gene status. The result of meta-analysis showed that hazard ratio (HR)=3.04, 95% CI 2.30－4.01, P=0.000. That was statistically significant. It indicated that the OS of CRLM patients with BRAF mutation was shortened after hepatectomy. HR funnel plot of OS was basically symmetrical, and no obvious publication bias was found. Three studies reported 1 237 CRLM patients'DFS after hepatectomy through stratified analysis by BRAF gene status. The mutation rate of BRAF was 9.62%. The result of meta-analysis showed that HR=2.07, 95%CI (1.06－4.03), P=0.03. That was statistically significant. It indicated that the DFS of CRLM patients with BRAF mutation was shortened after hepatectomy. HR funnel plot of DFS was asymmetric, and it was uncertain whether there was publication bias, which may be related to the small sample size included in the study.

Conclusion

·BRAF mutation is a biomarker of poor prognosis in CRLM patients after hepatectomy. It is related to poor OS, and more studies are needed to confirm the relationship with poor DFS.

Key words: BRAF gene, mutation, colorectal cancer, liver metastasis, prognosis

CLC Number:

R657.3

Sheng CHENG, Yi ZHAO, Yong-chen WANG, Ping HUANG. Meta-analysis of the effect of BRAF gene mutation on the prognosis of colorectal cancer patients with liver metastases after hepatectomy[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(6): 786-792.

Figures/Tables 7

TrendMD

References 46

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Study	n	BRAF mutation / n(%)	OS or DFS			Source of genetic testing issue of BRAF mutation / %	Preoperative and/or postoperative chemotherapy
Study	n	BRAF mutation / n(%)	Index	BRAF-MT	BRAF- WT	Source of genetic testing issue of BRAF mutation / %	Preoperative chemotherapy only / %	Preoperative chemotherapy only / %	Preoperative and postoperative chemotherapy / %	Specific drugs and treatment
Teng ^[26], 2012	292	6 (2.1)	mOS	8.20 months	19.30 months	Liver / 100	22.60	83.90	11.30	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
			1-year OS	33.00%	94.70%
Umeda^[27], 2013	100	3 (3.0)	3-year OS	0	77.10%	Liver / 100	33.00	85.00	NA	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
			5-year OS	0	65.10%
Schirripa^[28], 2015	309	12 (3.9)	mOS	22.60 months	66.30 months	Liver / 16.5, colorectal/ 17.5, both / 66.0	50.00	21.00	36.00	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
Margonis^[29], 2018	849	43 (5.5)	3-year OS	12.10%	36.50%	Liver or colorectal / NA	67.70	62.40	NA	NA
			20-month OS	55.00%	85.00%
Lin ^[30], 2018	139	10 (7.2)	40-month OS	25.00%	60.00%	Colorectal / 100	23.00	100.00	23.00	5-FU, OXA, IRI, XEL
			60-month OS	0	55.00%
			20-month DFS	10.00%	55.00%
			40-month DFS	0	40.00%
Bachet^[31], 2019	249	66 (26.5)	3-year OS	54.00%	82.90%	Liver or colorectal / NA	82.70	NA	74.70	5-FU, OXA,targeted drugs, HAI
			mOS	52.70 months	>52.70 months
			1-year DFS	46.00%	55.40%
			3-year DFS	19.00%	27.80%
			5-year DFS	10.00%	13.00%
Ruzzenente^[32], 2019	784	17 (2.2)	5-year OS	0	47.60%	Liver or colorectal / NA	100.00	NA	NA	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)

Study	n	BRAF mutation / n(%)	OS or DFS			Source of genetic testing issue of BRAF mutation / %	Preoperative and/or postoperative chemotherapy
Study	n	BRAF mutation / n(%)	Index	BRAF-MT	BRAF- WT	Source of genetic testing issue of BRAF mutation / %	Preoperative chemotherapy only / %	Preoperative chemotherapy only / %	Preoperative and postoperative chemotherapy / %	Specific drugs and treatment
Teng ^[26], 2012	292	6 (2.1)	mOS	8.20 months	19.30 months	Liver / 100	22.60	83.90	11.30	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
			1-year OS	33.00%	94.70%
Umeda^[27], 2013	100	3 (3.0)	3-year OS	0	77.10%	Liver / 100	33.00	85.00	NA	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
			5-year OS	0	65.10%
Schirripa^[28], 2015	309	12 (3.9)	mOS	22.60 months	66.30 months	Liver / 16.5, colorectal/ 17.5, both / 66.0	50.00	21.00	36.00	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)
Margonis^[29], 2018	849	43 (5.5)	3-year OS	12.10%	36.50%	Liver or colorectal / NA	67.70	62.40	NA	NA
			20-month OS	55.00%	85.00%
Lin ^[30], 2018	139	10 (7.2)	40-month OS	25.00%	60.00%	Colorectal / 100	23.00	100.00	23.00	5-FU, OXA, IRI, XEL
			60-month OS	0	55.00%
			20-month DFS	10.00%	55.00%
			40-month DFS	0	40.00%
Bachet^[31], 2019	249	66 (26.5)	3-year OS	54.00%	82.90%	Liver or colorectal / NA	82.70	NA	74.70	5-FU, OXA,targeted drugs, HAI
			mOS	52.70 months	>52.70 months
			1-year DFS	46.00%	55.40%
			3-year DFS	19.00%	27.80%
			5-year DFS	10.00%	13.00%
Ruzzenente^[32], 2019	784	17 (2.2)	5-year OS	0	47.60%	Liver or colorectal / NA	100.00	NA	NA	5-FU, OXA, IRI, anti-EGFR (Beva, Cetu)

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