Prognostic Role Of Human Epidermal-growth-factor Receptor 2(HER-2) In Colorectal Cancer

BackgroundColorectal cancer(CRC)is one of the most common gastrointestinal malignancies worldwide and the third most common cancer in China.Both genomic and epigenetic alterations are common in CRC and are the driving forces in the process of tumorigenesis.Human epidermal growth factor receptor 2(HER-2),as a biomarker,its role for prognosis in CRC patients remains uncertain.The aim of this study was to evaluate HER-2 overexpression and prognosis of colorectal cancer survival.MethodA comprehensive literature search of the Pub Med and EMBASE databases(up to December 2018)was conducted to identify studies on the association between HER-2overexpression and CRC survival.The search strategy included terms for:“Colorectal Neoplasm”,(“Colorectal Carcinoma”,“Colorectal Cancer”and“Colorectal Tumor”),“HER-2”(“Erb B-2 Receptor”“Proto-Oncogene Proteins c-erb B-2”“Oncogene Protein HER 2”),“Prognoses”(“Recurrence”,“Survival”).And the language was limited to English.HR was used in this time-to-event analysis its corresponding 95%CI was used to estimate the overall survival value of each study.Heterogeneity was considered significant when I~2was greater than 50%,then the random-effects model was used;otherwise,the fixed-effects model was used.The significance of the pooled HR was determined by Z test,and P?0.05 was considered statistically significant.Between-study heterogeneity was assessed using the Cochran Q test and I~2statistic,when I~2>50%indicating substantial heterogeneity between studies.Funnel plot asymmetry implied results were subject to publication bias,whereas symmetry implied a lack of bias,and P?0.1 was considered statistically significant.All statistical calculations were undertaken by Stata software(Version 12.0).ResultsThe initial search retrieval 341 of related paper,eventually 15 papers conform to the requirements of the paper.CRC Patients sum to 3733,including 969 CRC patients with HER-2 positive.The random effects models were performed with the Der Simonian Laird method,and data analysis showed that HER-2 overexpression status was not significantly related to the overall survival in CRC patients(HR=1.00,95%CI 0.76-1.25),with 95%CI include 1.Heterogeneity was considered significant(I~2=67.2%).In the subgroup analysis,5 studies are from the Asian subgroup,including Japan,South Korea,China.Asian subgroup patients showed pooled HR was 1.43(95%CI:1.03-1.84),with 95%CI do not include 1,but the lower 95%CI is extremely close to 1.It showed that the association between HER-2 overexpression and CRC survival was weak.Heterogeneity was not considered statistical significance(I~2=24.5%,P=0.258).The rest 10 studies are from non-Asian subgroup,including Germany,Austria,Brazil,Poland,France,America and England.Non-Asian CRC patients with HER-2 positive sum to729.Data analysis showed pooled HR was 0.84(95%CI:0.59-1.10),with 95%CI include 1.Heterogeneity was considered significant(I~2=66.2%,P=0.002).The included study is asymmetrically distributed on both sides of the midline,with P>0.1 for both Egger's and Begg's tests,suggesting that the publication bias was not statistically significant.ConclusionThe present meta-analysis demonstrated HER-2 overexpression is not closely associated with poorer prognostic outcome of patients with CRC.The results should be cautiously taken into consideration in view of the limitation of differences in selection,and publication and language biases.More large-scale,well-designed,randomized controlled researches are needed to support and validate in the future.