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Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer.

ABSTRACT: Pancreatic cancer is associated with poor prognosis due to limited therapeutic options. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in some cancers and may be regarded as a poor prognostic factor. Yet, its role in pancreatic cancer remains unclear. This study aimed to investigate the expression and functions of ERCC3 in pancreatic cancer patients and its relation with clinicopathological features. Our data suggested that the protein expression level of ERCC3 was higher in tumor tissues than in adjacent tissues. In addition, the expression of ERCC3 has shown to be associated with the tumor extent (p=0.035). Besides, analysis of the dataset in The Cancer Genome Atlas (TCGA) revealed that high expression of ERCC3 was associated with poor overall survival in pancreatic cancer patients (p=0.0136). In Cox regression analysis, ERCC3 was an independent prognostic factor for overall survival in pancreatic cancer (p<0.001). Furthermore, our in vitro data further suggested that the overexpression of ERCC3 significantly promoted pancreatic cancer (BxPC-3, CFPAC-1, and PANC-1 cells) proliferation, invasion, and migration. Taken together, this study suggested that high expression of ERCC3 might be a poor prognostic factor in human pancreatic cancer and might be used as a promising therapeutic target for pancreatic cancer treatment.

SUBMITTER: Wang S

PROVIDER: S-EPMC8040713 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer.

Wang Shujie S Liu Wenjing W Ni Yueli Y Wang Lifeng L Zhu Yuzhi Y Shi Qiong Q Yi Zihan Z Wang Wenjie W Liu Lili L Yang Lijuan L Kuang Yingmin Y Zhu Yuechun Y Zhang Qiao Q Yang Zhe Z

Journal of Cancer 20210305 9

Pancreatic cancer is associated with poor prognosis due to limited therapeutic options. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in some cancers and may be regarded as a poor prognostic factor. Yet, its role in pancreatic cancer remains unclear. This study aimed to investigate the expression and functions of ERCC3 in pancreatic cancer patients and its relation with clinicopathological features. Our data suggest ...[more]

PMID: 33854616

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Project description:AimTo investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer.MethodsIn our previous study of human whole-genome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records.ResultsMR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stage I-IV carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043].ConclusionMR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.

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Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer.

Publications

Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer.

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