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.

KEYWORDS:

• Synaptotagmin-4
• synaptotagmin-9
• Synaptotagmin-14
• prognostic values
• gastric cancer

Highlights

1.The expressions of SYT4, SYT9 and SYT14 were up-regulated in gastric cancer (GC).

2. The over-expression of SYT4, SYT9 and SYT14 contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) for GC patients.

3. The expressions of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC.

4. SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.

Availability of data and materials

The HTSeq FPKM data, methylation450 profile, and clinical data with GC were downloaded from the TCGA database via UCSC Xena (https://xena.ucsc.edu/). All data generated in this study are included in this published article.

Acknowledgements

We appreciated Yu-qiang Nie for revising the manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Authors’ contributions

De-feng Li, Ben-hua Wu, Li-sheng Wang and Jun Yao were responsible for design of the study and reviewed the manuscript. Mei-feng Yang, Xing-xing Long and Hong-sai Hu drafted the manuscript. Yu-ling Bin, Xuan-ming Chen, Ben-hua Wu and De-feng Li obtained and calculated the data. Quan-zhou Peng, Jun Yao and Li-sheng Wang performed IHC. De-feng Li, Jun Yao and Li-sheng Wang was responsible for revising manuscript. All authors have read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by Natural Science Foundation of Guangdong Province (No.2018A0303100024), Three Engineering Training Funds in Shenzhen (No. SYLY201718, No. SYJY201714 and No. SYLY201801), Technical Research and Development Project of Shenzhen (No. JCYJ20150403101028164, No. JCYC20170307100911479 and No. JCYJ20190807145617113), National Natural Science Foundation of China (No.81800489), Scientific research project of Hunan Education Department (No.18C0459) and Guangdong Province Health Planning Commission (No.A2021117).