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Overexpression of HS6ST2 is associated with poor prognosis in patients with gastric cancer.

ABSTRACT: The purpose of the present study was to investigate the clinical significance of the expression of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in gastric cancer (GC). The Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array (Affymetrix; Thermo Fisher Scientific, Inc., Waltham, MA, USA) was used to identify differentially expressed genes in GC tissues vs. adjacent non-tumor gastric tissues. Candidate genes were further verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). In addition, an independent dataset was obtained from the Gene Expression Omnibus, and a survival analysis was performed. Microarray analysis demonstrated that HS6ST2 was upregulated (>12-fold) in GC tissues compared with that in adjacent non-tumor tissues. RT-qPCR and IHC analysis of HS6ST2 in GC tissues and adjacent non-tumor tissues confirmed the microarray data. Furthermore, a positive association was demonstrated between HS6ST2 overexpression with the depth of tumor invasion, distant metastasis, and tumor-node metastasis stage. Survival analysis revealed an association between patients with increased expression of HS6ST2 and a poor prognosis of gastric cancer. Cox regression analysis indicated that the expression of HS6ST2 was an independent negative prognostic factor for GC. The expression of HS6ST2 in GC was significantly associated with specific clinicopathological parameters and prognosis of disease, thus we propose that HS6ST2 may represent a novel biomarker for GC.

SUBMITTER: Jin Y

PROVIDER: S-EPMC5661401 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Overexpression of HS6ST2 is associated with poor prognosis in patients with gastric cancer.

Jin Yi Y He Jun J Du Jing J Zhang Ru-Xuan RX Yao Hai-Bo HB Shao Qin-Shu QS

Oncology letters 20170914 5

The purpose of the present study was to investigate the clinical significance of the expression of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in gastric cancer (GC). The Affymetrix GeneChip<sup>®</sup> Human Genome U133 Plus 2.0 Array (Affymetrix; Thermo Fisher Scientific, Inc., Waltham, MA, USA) was used to identify differentially expressed genes in GC tissues vs. adjacent non-tumor gastric tissues. Candidate genes were further verified by reverse transcription quantitative polymerase chai ...[more]

PMID: 29113266

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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.

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Overexpression of HS6ST2 is associated with poor prognosis in patients with gastric cancer.

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Overexpression of HS6ST2 is associated with poor prognosis in patients with gastric cancer.

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