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Overexpression of carboxypeptidase A4 (CPA4) is associated with poor prognosis in patients with gastric cancer.

ABSTRACT: CarboxypeptidaseA4 (CPA4) is a zinc-containing exopeptidases, and its aberrant expression has been implicated in cancer development and progression. However, few studies have investigated the association between CPA4 over-expression and clinical significance in gastric cancer (GC). In this study, we employed immunohistochemistry to evaluate the expression of CPA4 in gastric cancer tissues, and found that elevated CPA4 expression was detected in 64% (n=100) of primary GCs, but was weak or no staining in the normal mucosa. Clinical relevance analysis showed that positive staining for CPA4 was significantly associated with Tumor size, Stage, Lymph node metastasis, Depth of invasion and Distant metastasis. As tumor markers p53 and Ki67 are closely associated with tumor progression, we further analyzed the correlations between CPA4 levels and these two factors. We found that abnormal expression of CPA4 was positively associated with Ki67 (P=0.002) and reversely correlated with p53 (P=0.035) in GC. In Kaplan-Meier survival analysis, high levels of CPA4 were significantly associated with unfavorable survival in GC patients (P<0.001). Multivariate Cox regression model showed that high expression of CPA4 was an independent prognostic factor for GC patients. In conclusion, our results suggested that CPA4 was highly expressed in gastric cancer tissues. Overexpression of CPA4 can be used as an independent poor prognostic factor in gastric cancer.

SUBMITTER: Sun L

PROVIDER: S-EPMC5126350 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Overexpression of carboxypeptidase A4 (CPA4) is associated with poor prognosis in patients with gastric cancer.

Sun Lichao L Guo Chunguang C Yuan Hebao H Burnett Joseph J Pan Jian J Yang Zhihua Z Ran Yuliang Y Myers Ila I Sun Duxin D

American journal of translational research 20161115 11

CarboxypeptidaseA4 (CPA4) is a zinc-containing exopeptidases, and its aberrant expression has been implicated in cancer development and progression. However, few studies have investigated the association between CPA4 over-expression and clinical significance in gastric cancer (GC). In this study, we employed immunohistochemistry to evaluate the expression of CPA4 in gastric cancer tissues, and found that elevated CPA4 expression was detected in 64% (n=100) of primary GCs, but was weak or no stai ...[more]

PMID: 27904708

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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.

Project description:BackgroundNitric oxide (NO) and cyclic guanosine phosphate (cGMP) play important roles in blood pressure regulation, neurotransmitter delivery, renal function, and tumorigenesis and development. The intermediate link of this signaling pathway, soluble guanylyl cyclase (sGC), is particularly important. However, the role of the GUCY1A2 gene encoding the sGC α2 subunit is unknown.MethodsGene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. After screening for GUCY1A2 expression, the expression differences between gastric cancer (GC) tissues and adjacent noncancerous tissues were determined using R software. Quantitative real-time polymerase chain reaction (qRT-PCR) and meta-analysis were used to verify the result. The correlation between the expression of GUCY1A2 and clinicopathological parameters was explored by logistic regression. Then, Kaplan-Meier survival analysis and the Cox proportional hazards regression were used to evaluate the relationship between the expression of GUCY1A2 and the survival of GC patients. Finally, gene set enrichment analysis (GSEA) was used to explore and analyze the GC-related signaling pathways affected by high GUCY1A2 expression.ResultsWe found that GUCY1A2 was highly expressed in GC tissues compared to adjacent noncancerous tissues (P < 0.001). qRT-PCR (P < 0.001) and meta-analysis (SMD = 0.65, 95% CI: 0.20-1.10) confirmed the difference in GUCY1A2 expression. Logistic regression analysis showed that high expression of GUCY1A2 was associated with histological grade (OR=1.858 for poor vs. well or moderate, P = 0.004) and T stage (OR = 3.389 for T3 vs. T1, P = 0.025; OR = 3.422 for T4 vs. T1, P = 0.028). Kaplan-Meier curves indicated that GC patients with high expression of GUCY1A2 had a poor prognosis than that of patients with low expression. Univariate analysis indicated that GUCY1A2 and some clinicopathological parameters, such as age, pathological stage, and TNM stage, may predict poor prognosis. Multivariate analysis further confirmed that GUCY1A2 was an independent prognostic marker (HR = 1.699; 95%CI, 1.175-2.456; P = 0.005). GSEA showed that the high GUCY1A2 phenotype is significantly enriched for tumor-associated signaling pathways.ConclusionsGUCY1A2 is highly expressed in GC and may be used as a potential prognostic marker.

Dataset Information

Overexpression of carboxypeptidase A4 (CPA4) is associated with poor prognosis in patients with gastric cancer.

Publications

Overexpression of carboxypeptidase A4 (CPA4) is associated with poor prognosis in patients with gastric cancer.

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