Abstract
To investigate the correlation between ERCC1 expression levels in tumor tissue and peripheral blood lymphocytes (PBL) from patients with gastric cancer and assess the relationship between PBL DNA repair rate (DRR) and the efficacy of platinum chemotherapy. A total of 53 patients with gastric cancer receiving surgery and 20 controls were studied. ERCC1 protein expression in tumour tissue and PBL were determined by immunohistochemical staining. The PBL DRRs of 47 advanced patients and 20 controls were estimated by comet assay. The positive expression rates of ERCC1 were 67. 9%, 56. 6% and 10.0% in tumour tissues, PBLs of gastric cancer patients, and PBLs of the control group. PBL ERCC1 expression correlated with that in tissue (χ(2) = 15. 463, p=0.000). Pearson contingency coefficient=0.475). DRRs of cancer patients by tail length (TL) (Z=4. 662, p=0.000) and tail moment (TM) (Z=3. 827, p=0.000) were significantly lower than that of control group. When TL was applied as an indicator, the correlation between DRR and chemotherapy efficacy was significant (Spearman rank correlation r=0.327, p=0.032). Patients with low levels of DRR in PBL presented better short-term efficacy of chemotherapy than those with high levels of DRR. The ERCC1 expression in PBLs may indirectly reflect ERCC1 expression in gastric cancer tissues. Compared with non-cancer populations, patients with gastric cancer may have lower DNA repair capacity. DRR in PBL may predict the short-term efficacy of platinum-based chemotherapy for patients with advanced gastric cancer.
Highlights
Gastric cancer remains the second leading cause of cancer death, with an estimated three hundred thousand deaths in China every year
A total of 47 advanced gastric cancer patients were recruited to detect the association between the peripheral blood lymphocytes (PBL) DNA repair rate (DRR) and chemotherapy efficacy
PBL DRR of advanced gastric cancer patients measured with cisplatin treatment in vitro When The correlation between DRR (TL) was served as an indicator, the range of DRRs in cancer patients was 48.39%-100.00%
Summary
Gastric cancer remains the second leading cause of cancer death, with an estimated three hundred thousand deaths in China every year. Most of gastric cancer patients are treated with chemotherapy, for advanced cases, but the treatment efficacy is still poor. Platinum is an significant drug in gastric cancer chemotherapy. It causes platinum-DNA adducts that block transcription, leading to cytotoxicity and cell death. Nucleotide excision repair (NER) is one of several DNA repair pathways for correcting the DNA structures that arise from DNA damage (Rabik and Dolan, 2007). Excision repair cross-complementation 1 (ERCC1) is one of the key enzymes in the NER pathway (Niedernhofer et al, 2004). As shown by most studies, both ERCC1 mRNA and protein expression are negatively correlated with the efficacy of platinum (Matsubara et al, 2008; Ozkan et al, 2010)
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