DNA Repair Capacity In Peripheral Blood Lymphocytes Predicts Efficacy Of Patients With Gastric Cancer Treated With Platinum-based Chemotherapy

Background&Objiective: Most of gastric cancer patients are treated withchemotherapy,particularly for advanced cases,but the treatment efficacy is still poor.Platinum is an significant drug in gastric cancer chemotherapy.It causes platinum-DNAadducts that block transcription, leading to cytotoxicity and cell death. Excision repaircross-complementation1(ERCC1) is one of the key enzymes in the nucleotide excisionrepair pathway. As shown by most studies, ERCC1expression are negatively correlatedwith the efficacy of platinum. At present,analyses of ERCC1expression are mainlybased on tumor tissue samples from operative resection or gastroscopy. These bringpain to the patients and operate complicatedly.And when chemotherapy carried out,thesensitivity marker ERCC1expression may have changed. For these reasons, clinicalpractices require a simpler and more convenient method of detection beforeindividualized treatment can be realized for patients with gastric cancer. Many studieshave confirmed that PBLC and tumor cells carry the homologous gene. Therefore,theaim of the present study was to evaluate the correlation between the ERCC1expressionof gastric cancer patients in tumor tissue and PBLC. Furthermore,other DNA repairenzymes and mechanisms relate with platinum-based chemotherapy sensitivity.ERCC1only reflect DNA repair capacity in one stage of the complex mechanisms. A phenotypicDNA repair marker that may represent the sum of all genetic variants is desirable.Currently,The DNA repair rate(DRR), as an indicator, can represent the individual DNArepair capacity comprehensively. If DRR could predict platinum efficacy as a sensitivemarker,it would be more accurate for drug choice. Therefore,the aim of the present study was to evaluate the correlation between the DRR in PBLC of advanced gastriccancer patients and the efficacy of platinum-based chemotherapy.Methods: A total of53patients with gastric cancer receiving surgery werestudied.ERCC1protein expression in tumor tissue and PBLC were determined byimmunohistochemical staining. Another20cases of PBLCs with non-cancer peoplewere determined as control. The PBLC DRRs of47patients of advanced gastric cancerand20non-cancer people were detected by comet assay.43patients of advanced gastriccancer received platinum-based chemotherapy and evaluated efficacy.Results: The positive expression rates of ERCC1were67.9%,56.6%and10.0%intumor tissues, PBLCs of gastric cancer patients, and PBLCs of control group.There wasno correlation between the ERCC1expression and clinical and pathological factors.ThePBLC ERCC1expression correlated with the expression in tissue(χ2=15.463，p=0.000，Pearson contingency coefficient=0.475). There was no relationship between the DRRand clinical and pathological factors.The same situation also occured in the diseasecontrol rate.DRRs of cancer patients by tail length(TL)(Z=4.662,p=0.000) and tailmoment(TM)(Z=3.827,p=0.000) were significantly lower than that of control group.When TL was served as an indicator,the correlation between DRR and chemotherapyefficacy was significant(Spearman rank correlation r=0.327,p=0.032). Patients with lowlevels of DRR in PBLC presented better short-term efficacy of chemotherapy than thosewith high levels of DRR.Conclusion: The ERCC1expression in PBLCs may indirectly reflect ERCC1expressionin gastric cancer tissues. Compared with non-cancer populations,patients with gastriccancer may have lower DNA repair capacity.DRR in PBLC may predict the short-termefficacy for patients with advanced gastric cancer treated with platinum-based chemotherapy.