scholarly journals CAST as a Potential Oncogene From Machine Searching in Gastric Cancer Infiltrated with Macrophage and Associated with Lgr5

Author(s):  
Kuang-Tsu Yang ◽  
Chia-Jung Li ◽  
Renin Chang ◽  
Jui-Tzu Wang ◽  
Yih-Wen Tarng ◽  
...  

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Liangjun Yang ◽  
Zhipeng Hu ◽  
Jiajie Zhu ◽  
Qiting Liang ◽  
Hengli Zhou ◽  
...  

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan–Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.


2020 ◽  
Author(s):  
Jia-Xiang An ◽  
Ying-Ying Chen ◽  
Zhao-Sheng Ma ◽  
Wen-Jie Yu ◽  
Jin-Xi Hu ◽  
...  

Abstract Background: CXCL2 is a part of chemokine superfamily, which encodes secretory proteins involved in immune regulation and inflammation. The correlation between CXCL2 and prognosis of different cancers, tumor infiltrating lymphocytes are not clear. Methods: We analyzed the expression of CXCL2 and its effect on clinical prognosis through Oncomine database, Tumor Immune Estimation Resource (TIMER) website, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA were used to analyze the correlation between CXCL2 and the gene marker of immune infiltration. StarBase was used to predict the miRNA that may regulate CXCL2. The relationship between miR-532-5p and CXCL2 was detected by qRT-PCR. Kaplan-Meier plotter was used to evaluate the impact of miR-532-5p on clinical prognosis. Results: PrognoScan, Kaplan-Meier plotter and GEPIA database analysis showed that low expression of CXCL2 was associated with poor disease-specific survival time (DSS), relapse-free survival time (RFS) and overall disease survival (OS) in breast cancer patients. In addition, low expression of CXCL2 was associated with poor OS and RFS in patients with lymph node positive breast cancer. CXCL2 expression was positively correlated with the infiltration of B cells, CD4+T and CD8+T cells, neutrophils and dendritic cells (DCs) in BRCA, mainly in Luminal breast cancer. MiR-532-5p can directly regulate CXCL2 expression. High miR-532-5p expression is significantly correlated with HER2 negative, grade 2 and 3 and poor OS in patients with HER+ER- breast cancer. Conclusion: CXCL2 is closely related to the prognosis and immune infiltration level of breast cancer patients, it can be regulated by miR-532-5p.


2020 ◽  
Vol 19 ◽  
pp. 153303382097068
Author(s):  
Yu Xiao ◽  
Hongpan Zhang ◽  
Guobo Du ◽  
Xue Meng ◽  
Tingting Wu ◽  
...  

Objective: To analyze the expression and clinical significance of retinoic acid-induced protein 14 ( RAI14) in gastric cancer and its relationship with immune cell infiltration by mining databases such as Oncomine, TIMER, UALCAN, and Kaplan Meier Plotter. Methods: RAI14 expression in various cancer types was analyzed using the Oncomine and TIMER databases. We used the Kaplan-Meier Plotter and UALCAN databases to evaluate the impact of RAI14 on clinicopathological parameters in gastric cancer. The correlation between RAI14 expression and immune cell invasion was studied using TIMER. TIMER was also used to analyze the correlation between RAI14 expression and marker levels of tumor-infiltrating immune cells. Results: High RAI14 expression in gastric cancer was significantly associated with poor overall survival (OS; hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.53–2.15, P < 0.001) and poor progression-free survival (PFS; HR = 2.16, 95% CI = 1.77–2.65, P < 0.001). Furthermore, high RAI14 expression was significantly associated with poor prognosis of patients with stage 2–4 gastric cancer, but not with OS and PFS of stage 1 patients (OS P = 0.17; PFS P = 0.09), and patients with stage N0 PFS had nothing to do (PFS P = 0.238). RAI14 expression was positively correlated with the infiltration levels of monocytes, tumor-associated macrophages, macrophages, neutrophils, and Treg cells in gastric cancer. Besides, RAI14 expression was closely related to various marker genes in immune cells. Conclusion: RAI14 is highly expressed in gastric cancer, and its expression level is correlated with the prognosis of patients with gastric cancer. RAI14 plays also an important role in the recruitment and regulation of infiltrating immune cells and is, thus, expected to become a target for the optimal treatment of gastric cancer.


Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 547
Author(s):  
Wenjing Gong ◽  
Jianyuan Zeng ◽  
Jiafu Ji ◽  
Yongning Jia ◽  
Shuqin Jia ◽  
...  

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC.


2021 ◽  
Author(s):  
Zitong Li ◽  
Haoran Ke ◽  
Wenlin Deng ◽  
Fang Li ◽  
Siqi Wang ◽  
...  

Abstract Background: MAGEH1 is a critical gene for regulatory T cell function. However, correlations of MAGEH1 to prognosis and tumor-infiltrating cells in different cancers remain unclear. This study was to determine the prognostic impact of MAGEH1 as well as evaluate MAGEH1 expression and immune infiltrate relevance in gastric cancer.Methods: Oncomine, TIMER2.0, Kaplan-Meier Potter, PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas database were utilized to analyze the differential MAGEH1 expression and its prognostic value. The relationship between MAGEH1 and gene markers of immune infiltration was confirmed by TIMER2.0 and GEPIA.Results: The prognostic effect of MAGEH1 varied across cancers. Particularly in gastric cancer, highly expressed MAGEH1 showed a significant association with poor prognosis in multiple databases whereas was linked to a better prognosis in patients with adjuvant 5-fluorouracil therapy. MAGEH1 expression positively correlated with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells in stomach adenocarcinoma (STAD). Furthermore, MAGEH1 expression showed a strong link with markers for monocytes, macrophages, neutrophils and Tregs in STAD tissues.Conclusions: MAGEH1 can serve as a prognostic biomarker in gastric cancer and is related to immune infiltrates.


2020 ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang

Abstract Background: Replication factor C (RFC) is closely related to tumor progression and metastasis. However, the functional significance of RFC2 in hepatocellular carcinoma remains unclear.Materials and methods: In order to solve this problem, the expression of RFC2 in liver cancer patients was analyzed through ONCOMINE, UALCAN, human protein atlas. Survival analysis was conducted using Kaplan-Meier plotter and GEPIA. GO and KEGG enrichment analyses were carried out. The protein-protein interaction (PPI) network was performed through Metascape.Result: The transcription and protein level of RFC2 in HCC were overexpressed, which was significantly related to the clinical individual cancer stage and pathological tumor grade of HCC patients. In addition, in patients with liver cancer, higher RFC2 expression was found to be significantly correlated with shorter OS and DFS. Furthermore, the function of RFC2 in liver cancer was DNA replication, and its main mechanism was the phase transition of the cell cycle.Conclusion: RFC2 might promote the development of liver cancer. It could also be used as a novel biomarker for the prognosis of liver cancer.


2020 ◽  
Author(s):  
Xiaolong Chen ◽  
Zhixiong Xia ◽  
Yafeng Wan ◽  
Ping Huang

Abstract BackgroundHepatocellular carcinoma (HCC) is the third cancer-related cause of death in the world. Until now, the involved mechanisms during the development of HCC are largely unknown. This study aims to explore the driven-genes and potential drugs in HCC. MethodsThree mRNA expression datasets were used to analyze the differentially expressed genes (DEGs) in HCC. The bioinformatics approaches include identification of DEGs and hub genes, GO terms analysis and KEGG enrichment analysis, construction of protein–protein interaction network. The expression levels of hub genes were validated based on TCGA, GEPIA and the Human Protein Atlas. Moreover, overall survival and disease-free survival analysis of the hub genes were further conducted by Kaplan-Meier plotter and the GEPIA. DGIdb database was performed to search the candidate drugs for HCC. ResultsFinally, 197 DEGs were identified. The PPI network was constructed using STRING software. Then ten genes were selected and considered as the hub genes. The ten genes were all closely related to the survival of HCC patients. DGIdb database predicted 39 small molecules as the possible drugs for treating HCC. ConclusionsOur study provides some new insights into HCC pathogenesis and treatments. The candidate drugs may improve the efficiency of HCC therapy in future.


2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Yang ◽  
Fusheng Ge ◽  
Shuaibing Lu ◽  
Zhiming Shan ◽  
Liangqun Peng ◽  
...  

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p &lt; 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25–2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03–2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057–2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.


Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 198
Author(s):  
Ji Yeon Park ◽  
Byunghyuk Yu ◽  
Ki Bum Park ◽  
Oh Kyoung Kwon ◽  
Seung Soo Lee ◽  
...  

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.


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