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Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

ABSTRACT: Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expressions of SYT4, SYT9, and SYT14 were up-regulated, and negatively associated with their methylation levels in GC. Both the over-expression of SYT4, SYT9 and SYT14 and their hypomethylation levels contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) in GC. Moreover, the low expressions of several methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503, cg26158959, cg02269161, cg03226737, cg08185661, cg16437728, cg22723056 and cg24678137) were significantly correlated with an unfavorable OS and PFS in GC. Furthermore, the expression of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC. Collectively, our current finding suggested that SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.

SUBMITTER: Yang MF

PROVIDER: S-EPMC8806422 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

Yang Mei-Feng MF Long Xing-Xing XX Hu Hong-Sai HS Bin Yu-Ling YL Chen Xuan-Ming XM Wu Ben-Hua BH Peng Quan-Zhou QZ Wang Li-Sheng LS Yao Jun J Li De-Feng DF

Bioengineered 20211201 1

Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expression ...[more]

PMID: 34229539

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Project description:BackgroundBreast cancer (BC) is one of the most lethal malignant tumors and the leading cause of cancer-related death worldwide. Although early diagnostic techniques for BC have been well developed, 40% of cases are still diagnosed at the advanced stage, while for BC patients with distant metastases, the 5-year survival rate is usually lower than 30%. The Snail family, generally regarded as transcriptional repressors, has been indicated to be an essential prognostic factor in malignant tumors. However, limited data exist on public databases concerning the prognostic value of individual Snail family members in BC, especially SNAI3.MethodsData from public databases including cBioPortal for Cancer Genomics, Gene Expression Omnibus, UCSC Xena Browser, and Human Protein Atlas (HPA) were downloaded. Based on the Kaplan¬-Meier plotter platform, correlation of the three members of the Snail family and prognosis in BC were analyzed. Individual Snail family members and their co-expressed genes were respectively enriched on different pathways and biological processes via the functional enrichment analysis (FunRich) tool.ResultsHigh SNAI1 mRNA expression was associated with shorter distant metastasis-free survival (DMFS) in all BC patients regardless of PAM50 subtype. Conversely, high SNAI3 mRNA expression was associated with longer DMFS. Although the presence of SNAI2 expression was significantly associated with DMFS in the whole cohort, no significant correlation was found in patients with luminal A or HER2 subtype. For patients with the most diverse clinicopathological features, high SNAI1 expression was associated with poor survival, with the converse being true for SNAI3. However, the impact on prognosis of patients with different clinicopathological features produced by SNAI2 expression was inconclusive. Furthermore, we discovered that SNAI1 or SNAI2 and their co-expressed genes frequently enriched receptor tyrosine kinase (RTK) signaling and integrin-related pathways which mainly functioned on epithelial-mesenchymal transition and were further involved in several processes of signal transduction and cell communication. Furthermore, as SNAI3, along with its co-expressed genes, enriched immune-related pathways, it may thus play a role in mediating the immune system.ConclusionsOur analysis revealed that SNAI1 mRNA expression may potentially be a negative prognostic factor, whereas SNAI3 mRNA was associated with positive prognosis in BC. Therefore, the assessment of SNAI1 and SNAI3 expression may be valuable for predicting prognosis in BC patients.

Project description:Background: Gastric cancer (GC) is one of the most common and poor prognosis malignancy in the world. The Family with sequence similarity 83 (FAM83) comprises of eight members of A-H. Accumulating evidence confirmed important roles for FAM83 family in tumorigenesis and progression. However, the prognostic values of FAM83 family in GC still have not been clarified. Methods: ONCOMINE, UALCAN, GEPIA, THE HUMAN PROTEIN ATLAS, Kaplan-Meier Plotter, cBioPortal, DAVID, STRING and TIMER databases and R software were adopted in this study. Results: In this study, we demonstrated that the mRNA levels of FAM83 B/C/D/H were significantly up-regulated in stomach adenocarcinoma (STAD), but the protein level of FAM83G/H were remarkable lowly in STAD. Next, FAM83C/D/G/H were significantly associated with tumor stages in STAD patients. Then, the mutation rate of FAM83 family members in STAD patients was 46%, and the highest mutation rate was FAM83H (23%). Furthermore, the functions of FAM83 family and their 259 co-expression genes were primarily related to Shigellosis, RNA degradation and Ribosome biogenesis in eukaryotes pathway. Besides, we have established the prognostic model of FAM83 family in STAD, including the prognostic model of STAD patients (FAM83C/D/G), STAD with lymph node metastasis (FAM83C/D/G/H) and STAD with ERBB2 high expression (FAM83G/H). FAM83C/D high expression with a poor prognosis, while FAM83G/H high expression with a favorable prognosis of STAD. Additionally, we found that the expression of FAM83C/D/G/H were significantly correlated with the infiltration of six types of immune cells [B cells, CD8+T cells, CD4+T cells, macrophages and Myeloid dendritic cells (DC)], whereas CD4+T cells and Macrophage cells have higher risk scores (HR > 1) when FAM83C lowly expression and FAM83D highly expression. The risk score of NK cells was significantly reduced when FAM83G lowly expression and FAM83H highly expression (HR < 1). Conclusion: These findings suggested that FAM83C/D/G/H might play key roles in STAD tumorigenesis and progression, and FAM83C/D might be risk factors but FAM83G/H might be favorable prognostic factors for STAD patients. In addition, CD4+T cells and Macrophage cells may be the promoters of FAM83D in progression of STAD, while NK cells may promote the protective effect of FAM83H on STAD patients.

Dataset Information

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

Publications

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

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