| ObjectiveAs a new anticancer drug,PARP inhibitors targeting DNA repair pathway have made a breakthrough in breast cancer and ovarian cancer treatment,becoming a research hotspot in the field of cancer treatment,and are expected to be applied to other tumor indications in the near future.This study focused on the expression of PARP-1 and BRCA1 in colorectal cancer tissues;investigating the relationship between PARP-1,BRCA1 and clinicopathologic features as well as the prognosis of adjuvant chemotherapy patients;analyzing the correlation between PARP-1 and BRCA1 protein expression in colorectal cancer;exploring the correlation between PARP-1 expression and microsatellite(MS)status in colorectal cancer.The aim is to search for biomarkers that can effectively predict the efficacy and prognosis of colorectal cancer and provide theoretical basis for the application of PARP inhibitors in colorectal cancer.MethodsSamples of 120 patients with colorectal adenocarcinoma after surgical resection in the 940 hospital of the PLA joint logistic support force from From March 2017 to September 2017 were collected,while 40 cases of para-carcinoma normal tissues were randomly selected as controls(all tissues were confirmed by pathology).The expression levels of PARP-1 and BRCA1 proteins in the above tissues were detected by tissue chip technology and immunohistochemical staining.The medical records were reviewed and the patients who received adjuvant chemotherapy were followed up.IBM SPSS Statistics 25 statistical software was used for analysis and processing.Χ2 test was used to compare the sample rates of counting data between the two groups.P<0.05 was considered statistically significant.Nonparametric test mann-Whitney U test was used to compare the differences among the ordered data groups,and P<0.05 was considered statistically significant.Partial correlation was used for correlation analysis,and P<0.05 was considered statistically significant.In survival analysis,kaplan-Meier was used to explore the relationship between the expression levels of PARP-1 and BRCA1 and 3-year PFS in patients receiving adjuvant chemotherapy.The difference between groups was tested by log-rank.P<0.05 was considered statistically significant.Results1.The total positive rate of PARP-1 in colorectal cancer tissues was 62.50%(75/120),and the positive rate of parP-1 in paracancerous normal tissues was 7.50%(3/40).The positive rate of PARP-1 in cancer tissues was higher than that in paracancerous normal tissues(P<0.05).The PARP-1 positive rate was 53.13%(17/32)in the left colon cancer tissue,41.67%(10/24)in the right colon cancer tissue,and 75.00%(48/64)in the rectal cancer tissue,with statistically significant difference(P<0.05).The positive rate of PARP-1 in moderately and highly differentiated colorectal cancer was 67.62%(71/105),and 26.67%(4/15)in poorly differentiated colorectal cancer.The positive rate of PARP-1 in moderately and highly differentiated colorectal cancer was higher than that in poorly differentiated colorectal cancer,and the difference was highly statistically significant.There were no statistically significant differences in the positive rate of PARP-1 among colorectal cancer patients in gender,age,tumor size,invasion depth,lymph node metastasis,distant metastasis,TNM stage,etc.(P>0.05)2.Among the patients receiving postoperative adjuvant chemotherapy,the average PFS of PARP-1 negative and positive patients was 30.43 months(95%CI: 26.45-34.42)and 24.63 months(95%CI: 20.38-28.89),respectively.The survival graph showed that the PFS of PARP-1 negative patients was higher than that of PARP-1 positive patients.3.The positive rates of PARP-1 in MSI-H,MSI-L and MSS colorectal cancer were 54.54%(12/22),52.94%(9/17)and 66.67%(54/81),respectively,and the difference between the three groups was not statistically significant(P>0.05).4.The positive rate of BRCA1 in colorectal cancer tissues was 78.3%(94/120)and 87.5%(35/40)in adjacent normal tissues,which was lower than that in adjacent normal tissues(P<0.05).The positive rate of BRCA1 in moderately and highly differentiated colorectal cancer was 83.81%(88/105),and 40.00%(6/15)in poorly differentiated colorectal cancer.The positive rate of BRCA1 in moderately and highly differentiated colorectal cancer was higher than that in poorly differentiated colorectal cancer,and the difference was highly statistically significant(P<0.05).There was no significant difference in the positive rate of BRCA1 in age,gender,tumor site,tumor size,invasion depth,lymph node metastasis,distant metastasis,TNM stage(P>0.05).5.Among the patients receiving postoperative adjuvant chemotherapy,the 3-year mean PFS of BRCA1 positive and negative patients were 24.74 months(95%CI: 20.93-28.54)and 33.39 months(95%CI: 30.05-36.72),respectively.The mean PFS of BRCA1 positive patients was lower than that of negative patients(P<0.05).The survival graph showed that the PFS of BRCA1 negative patients was higher than that of positive patients.6.In colorectal cancer tissues,12.5%(15/120)were PARP-1 and BRCA1 negative;9.17%(11/120)were BRCA1 negative while PARP-1 positive;25%(30/120)were BRCA1 positive while PARP-1 negative;53.3%(64/120)were PARP-1 and BRCA1 positive,and there was no correlation between the expression of PARP-1 and BRCA1 positive(P>0.05).Conclusion1.The expression of PARP-1 is related to the differentiation degree of colorectal cancer,and may be an influential factor affecting the prognosis of chemotherapy patients.Detection of PARP-1 expression has certain value in the stratification and treatment of colorectal cancer,and is of great significance in evaluating the potential therapeutic effect of PARP inhibitors in colorectal cancer.2.BRCA1 expression is related to the differentiation degree of colorectal cancer and the prognosis of chemotherapy patients.Therefore,BRCA1 molecular characteristics can not only be used as a marker for the stratification of colorectal cancer patients,but also are extremely important for in-depth understanding of the mechanism of chemotherapy sensitivity.3.There was no correlation between PARP-1 and BRCA1 expression in colorectal cancer. |
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