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High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma.

ABSTRACT: Stomach adenocarcinoma (STAD) is the most pathological type of gastric cancer. ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18) plays an essential role in organ development and tumorigenesis; however, its function in STAD, and its impact on clinical outcome remain unclear. Thus, the present study aimed to investigate the association between ADAMTS18 expression and the prognosis of patients with STAD. Data from 300 patients with STAD in The Cancer Genome Atlas (TCGA) database were analyzed, and the median survival time and overall survival (OS) rate of these patients were assessed. Subsequently, 40 paired tumor and non-tumor tissue samples from patients with STAD were collected, and the relative ADAMTS18 mRNA expression levels were determined. Results from TCGA database demonstrated that high tumor ADAMTS18 expression was associated with a poorer prognosis in patients with STAD. Similarly, results from the assessed patient cohort indicated that ADAMTS18 expression was significantly higher in STAD tissues compared with non-tumor tissues. Furthermore, ADAMTS18 expression was significantly associated with tumor differentiation, lymph node metastasis and tumor node metastasis stage. Taken together, these results suggest that ADAMTS18 is highly expressed in STAD tissues, and thus may act as a potential indicator of poor prognosis in patients with STAD.

SUBMITTER: Jiang K

PROVIDER: S-EPMC7491029 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma.

Jiang Kaiyuan K Li Lei L Xie Yubo Y Xie Dongyi D Xiao Qiang Q

Oncology letters 20200908 5

Stomach adenocarcinoma (STAD) is the most pathological type of gastric cancer. ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18) plays an essential role in organ development and tumorigenesis; however, its function in STAD, and its impact on clinical outcome remain unclear. Thus, the present study aimed to investigate the association between ADAMTS18 expression and the prognosis of patients with STAD. Data from 300 patients with STAD in The Cancer Genome Atlas (TCGA) database ...[more]

PMID: 32963617

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Project description:Background: The role of RASGRF2 has been verified in the development of various cancers. However, its roles in stomach adenocarcinoma (STAD) are still under investigation. Methods: RASGRF2 transcript-level data and the associated clinical information from patients with STAD were extracted from The Cancer Genome Atlas (TCGA). Diagnostic and prognostic values of RASGRF2 were analyzed using receiver-operator characteristics (ROC) analysis, correlation analysis, and survival analysis in conjunction with a prognostic model. In addition, gene expression profiles, differentially-expressed genes for co-varying expression, and a differential expressed genes (DEG) protein-protein interaction network for influential nodes were also analyzed. To identify the molecular role of RASGRF2 in STAD, gene ontology (GO) term, Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway, and gene set enrichment analysis (GSEA)-mediated functional module enrichment analyses were conducted. The relationship between RASGRF2 and gene signature-based predicted immune cell infiltration patterns were also investigated. To validate the bioinformatic findings, RASGRF2 protein expression was investigated in vitro using western blot and immunohistochemistry. Furthermore, relationships among RASGRF2 protein expression, clinicopathologic characteristics, and patient survival were analyzed. Results: Bioinformatic analysis revealed a significantly higher RASGRF2 transcript level in STAD tissue, which was positively associated with the T stage, histological type, histological grade, and TP53 status. Moreover, the RASGRF2 transcript level indicated poor overall survival in STAD patients (hazard ratio = 1.47, P = 0.023). Multivariate Cox regression analysis showed that primary therapy outcome, age, and RASGRF2 transcript level were independent prognostic factors for survival, and the C-index of a nomogram was 0.695. Additionally, 159 genes were differentially expressed according to RASGRF2 transcript levels; 15 exhibited co-varying expression, and 13 were identified as influential nodes. The DEG-list was significantly enriched for several GO terms, biological pathways, and functional modules, including MAPK, RAS, ERK, and immunoregulatory pathways. RASGRF2 transcript levels were significantly positively correlated with infiltration levels of Tem, Macrophages, pDCs, and NK cells. Validation analysis showed similar results for the RASGRF2 protein expression level in both in vitro analyses. Conclusion: Bioinformatic predictions combined with in vitro validation suggest that RASGRF2 plays diagnostic and prognostic roles and serves as a negative protective molecular factor in STAD patients.

Project description:Purpose: Glioma is the most common malignant brain tumor. The molecular mechanisms underlying its malignancy are not fully understood. LAMC1, which encodes extracellular matrix protein laminin ?1, has been implicated in some malignant tumors but has not been systematically evaluated in glioma. The aim of this study was to evaluate the expression of LAMC1 and its clinical significance. Patients and methods: LAMC1 protein expression in 52 fresh-frozen specimens of different pathological grade gliomas and 5 normal brain tissues was detected by Western blotting. Immunohistochemistry was used to detect LAMC1 protein expression in another set of 76 glioma tissues and 8 normal brain tissues. The associations between clinicopathological factors and LAMC1 expression were analyzed. A log-rank test and a multivariate Cox proportional hazards model were used to determine the relationship between LAMC1 expression and patient prognosis. The expression of LAMC1 at the mRNA level was analyzed in the TCGA database. Results: LAMC1 was highly expressed in high-grade glioma tissues, with moderate expression in low-grade gliomas, and weak or no expression in normal brain tissues, as detected by Western blotting and immunohistochemistry. A chi-square test indicated that LAMC1 expression was associated with pathological grade but not with other clinicopathological factors, such as age, sex, and tumor size. LAMC1 expression at the mRNA level was upregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue in the TCGA database. The Kaplan-Meier plot and log-rank test in our patient series showed that high LAMC1 expression was significantly associated with shorter survival, which was consistent with the TCGA database analysis. A multivariate Cox proportional hazards model revealed that LAMC1 expression, WHO grade, and surgery procedure were significantly correlated with overall survival and progression-free survival. Conclusion: These results demonstrated that LAMC1 may play an important role in glioma progression and may be used in the diagnosis, prognosis, and targeted therapy of glioma patients.

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High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma.

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High ADAMTS18 expression is associated with poor prognosis in stomach adenocarcinoma.

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