scholarly journals Prognostic value and biological significance of GUCY1A2 in gastric cancer: a bioinformatics analysis

Author(s):  
Shan Huang ◽  
Min Wei ◽  
Mengyuan Zhu ◽  
Xiaofen Pan

Abstract Background: Guanylate cyclase 1 soluble subunit alpha 2 (sGCα2), also known as GUCY1A2, was reported to be upregulated and promoted tumorigenesis in some cancers. But whether GUCY1A2 was abnormally expressed and the prognostic value in gastric cancer was unknown. The current study aimed to find out the prognostic value of GUCY1A2 in gastric cancer by analyzing data from The Cancer Genome Atlas (TCGA). Methods: Wilcoxon signed-rank test, cox regression analysis and multivariant analysis were used to analyze the relationship between clinical characteristic and GUCY1A2 expression level. Kaplan-Meier method was used to analyze the association of GUCY1A2 and overall survival. Gene set enrichment analysis (GSEA) was used to identify GUCY1A2-related signaling pathway. Results: Compared to normal tissue, expression of GUCY1A2 was significantly increased in gastric cancer (p=0.000). Increased GUCY1A2 was associated with advance T stage (p=0.012) and poor survival (p=0.022). Univariate analysis showed that high GUCY1A2 expression was associated with a poor overall survival (HR:1.44, 95% confidence interval [CI]: 1.03-2.02, p=0.03). Multivariate analysis indicated that GUCY1A3 remained an independent prognostic predictor of overall survival (HR:1.75, 95% confidence interval [CI]: 1.20-2.56, p=0.00). GSEA revealed that calcium signaling pathway, MAPK signaling pathway, TGF-β signaling pathway and Wnt signaling pathway were enriched in GUCY1A2 high expression phenotype. Conclusions: GUCY1A2 maybe a potential prognostic predictor of poor survival in gastric cancer. Calcium signaling pathway, MAPK signaling pathway, TGF-β signaling pathway and Wnt signaling pathway may be the key signaling pathway regulated by GUCY1A2.

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.


2021 ◽  
Author(s):  
Xiaofen Pan ◽  
Xingkui Tang ◽  
Minling Liu ◽  
Xijun Luo ◽  
Mengyuan Zhu ◽  
...  

Abstract BackgroundTumor microenvironment consists of tumor cells, immune cells and other matric components. Tumor infiltration immune cells are associated with prognosis. But all the current prognosis evaluation system dose not take tumor immune cells other matrix component into consideration. In the current study, we aimed to construct a prognosis predictive model based on tumor microenvironment.MethodCIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. Immune cell infiltration (ICI) scores of each patient were determine by principal-component analysis. Patients were divided to high and low ICI score groups. Survival, gene expression and somatic mutation of the two groups were compared.ResultsPatients with no lymph node invasion, no metastasis, T1-2 disease and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and WNT signaling pathway were enriched in high ICI score group. Immune-checkpoint genes and immune-activity associated genes were significantly decreased in high ICI score. Patients in high ICI score group had better survival than low ICI score group. Prognostic value of ICI score was independent of TMB.ConclusionICI score might serve as an independent prognostic biomarker in colon cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xingkui Tang ◽  
Minling Liu ◽  
Xijun Luo ◽  
Mengyuan Zhu ◽  
Shan Huang ◽  
...  

The current study aimed to construct a prognostic predictive model based on tumor microenvironment. CIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration (ICI) landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. ICI scores of each patient were determined by principal component analysis. Patients were divided into high and low ICI score groups. Survival, gene expression, and somatic mutation of the two groups were compared. We found that patients with no lymph node invasion, no metastasis, T1–2 disease, and stage I–II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and Wnt signaling pathway were enriched in the high ICI score group. Immune-checkpoint and immune-activity associated genes were decreased in high ICI score patients. Patients in the high ICI score group had better survival. Prognostic value of ICI score was independent of tumor mutational burden (TMB). The ICI score model constructed in the current study may serve as an independent prognostic biomarker in colon cancer.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Wu Song ◽  
Yujie Yuan ◽  
Liang Wang ◽  
Weiling He ◽  
Xinhua Zhang ◽  
...  

Objective.The study was designed to explore the prognostic value of examined lymph node (LN) number on survival of gastric cancer patients without LN metastasis.Methods.Between August 1995 and January 2011, 300 patients who underwent gastrectomy with D2 lymphadenectomy for LN-negative gastric cancer were reviewed. Patients were assigned to various groups according to LN dissection number or tumor invasion depth. Some clinical outcomes, such as overall survival, operation time, length of stay, and postoperative complications, were compared among all groups.Results.The overall survival time of LN-negative GC patients was50.2±30.5months. Multivariate analysis indicated that LN dissection number(P<0.001)and tumor invasion depth(P<0.001)were independent prognostic factors of survival. The number of examined LNs was positively correlated with survival time(P<0.05)in patients with same tumor invasion depth but not correlated with T1 stage or examined LNs>30. Besides, it was not correlated with operation time, transfusion volume, length of postoperative stay, or postoperative complication incidence(P>0.05).Conclusions.The number of examined lymph nodes is an independent prognostic factor of survival for patients with lymph node-negative gastric cancer. Sufficient dissection of lymph nodes is recommended during surgery for such population.


2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.


Author(s):  
Soshi Hori ◽  
Michitaka Honda ◽  
Hiroshi Kobayashi ◽  
Hidetaka Kawamura ◽  
Koichi Takiguchi ◽  
...  

Abstract Objective The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. Methods This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. Results A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P &lt; 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04–1.85): 1.69 (95% confidence interval: 1.27–2.27). Conclusions The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.


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