Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

SHMT2 is Associated with Tumor Purity, CD8+ T Immune Cells Infiltration, and a Novel Therapeutic Target in Four Different Human Cancers

Author(s): Muhammad Usman, Yasir Hameed*, Mukhtiar Ahmad, Muhammad Junaid Iqbal, Aghna Maryam, Afshan Mazhar, Saima Naz, Rida Tanveer, Hina Saeed, Bint-e-Fatima, Aneela Ashraf, Alishba Hadi, Zahid Hameed, Eman Tariq and Alia Sumyya Aslam

Volume 23, Issue 2, 2023

Published on: 01 March, 2022

Page: [161 - 176] Pages: 16

DOI: 10.2174/1566524022666220112142409

Price: $65

conference banner
Abstract

Aims: This study was launched to identify the SHMT2 associated Human Cancer subtypes.

Background: Cancer is the 2nd leading cause of death worldwide. Previous reports revealed the limited involvement of SHMT2 in human cancer. In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2.

Objective: We aim to comprehensively analyze the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Earlier, limited knowledge exists in the medical literature regarding the involvement of Serine Hydroxymethyltransferase 2 (SHMT2) in human cancer.

Methods: In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Pan-cancer transcriptional expression profiling of SHMT2 was done using UALCAN while further validation was performed using GENT2. For translational profiling of SHMT2, we utilized Human Protein Atlas (HPA) platform. Promoter methylation, genetic alteration, and copy number variations (CNVs) profiles were analyzed through MEXPRESS and cBioPortal. Survival analysis was carried out through Kaplan–Meier (KM) plotter platform. Pathway enrichment analysis of SHMT2 was performed using DAVID, while the gene-drug network was drawn through CTD and Cytoscape. Furthermore, in the tumor microenvironment, a correlation between tumor purity, CD8+ T immune cells infiltration, and SHMT2 expression was accessed using TIMER.

Results: SHMT2 was found overexpressed in 24 different subtypes of human cancers and its overexpression was significantly associated with the reduced Overall survival (OS) and Relapse-free survival durations of Breast cancer (BRCA), Kidney renal papillary cell carcinoma (KIRP), Liver hepatocellular carcinoma (LIHC), and Lung adenocarcinoma (LUAD) patients. This implies that SHMT2 plays a significant role in the development and progression of these cancers. We further noticed that SHMT2 was also up-regulated in BRCA, KIRP, LIHC, and LUAD patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of SHMT2 enriched genes in five diverse pathways. Furthermore, we also explored some interesting correlations between SHMT2 expression and promoter methylation, genetic alterations, CNVs, tumor purity, and CD8+ T immune cell infiltrates.

Conclusion: Our results suggested that overexpressed SHMT2 is correlated with the reduced OS and RFS of the BRCA, KIRP, LIHC, and LUAD patients and can be a potential diagnostic and prognostic biomarker for these cancers.

Keywords: SHMT2, Biomarker, Cancer, Diagnostic, Tumor purity, CD8+ T immune cells infiltration.

« Previous Next »
[1]
Misaghi A, Goldin A, Awad M, Kulidjian AA. Osteosarcoma: a comprehensive review. SICOT J 2018; 4: 12.
[http://dx.doi.org/10.1051/sicotj/2017028] [PMID: 29629690]
[2]
Czarnecka AM, Synoradzki K, Firlej W, et al. Molecular biology of osteosarcoma. Cancers (Basel) 2020; 12(8): E2130.
[http://dx.doi.org/10.3390/cancers12082130] [PMID: 32751922]
[3]
de Azevedo JWV, de Medeiros Fernandes TAA, Fernandes JV Jr, et al. Biology and pathogenesis of human osteosarcoma. Oncol Lett 2020; 19(2): 1099-116.
[PMID: 31966039]
[4]
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-78.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[5]
Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther 2018; 18(1): 39-50.
[http://dx.doi.org/10.1080/14737140.2018.1413939] [PMID: 29210294]
[6]
Subramaniam S, Jeet V, Clements JA, Gunter JH, Batra J. Emergence of microRNAs as key players in cancer cell metabolism. Clin Chem 2019; 65(9): 1090-101.
[http://dx.doi.org/10.1373/clinchem.2018.299651] [PMID: 31101638]
[7]
Ebrahimi N, Aslani S, Babaie F, et al. MicroRNAs implications in the onset, diagnosis, and prognosis of osteosarcoma. Curr Mol Med 2020; 21: 573-88.
[PMID: 33272173]
[8]
Lei W, Yan C, Ya J, Yong D, Yujun B, Kai L. MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4. BMC Cancer 2018; 18(1): 631.
[http://dx.doi.org/10.1186/s12885-018-4460-0] [PMID: 29866054]
[9]
Pu Y, Zhao F, Li Y, et al. The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene. BMC Cancer 2017; 17(1): 45.
[http://dx.doi.org/10.1186/s12885-016-3002-x] [PMID: 28073349]
[10]
Liang Z, Li X, Liu S, Li C, Wang X, Xing J. MiR-141-3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer. Biochem Biophys Res Commun 2019; 514(3): 699-705.
[http://dx.doi.org/10.1016/j.bbrc.2019.05.002] [PMID: 31078266]
[11]
Zhou Y, Zhong JH, Gong FS, Xiao J. MiR-141-3p suppresses gastric cancer induced transition of normal fibroblast and BMSC to cancer-associated fibroblasts via targeting STAT4. Exp Mol Pathol 2019; 107: 85-94.
[http://dx.doi.org/10.1016/j.yexmp.2018.11.014] [PMID: 30502321]
[12]
Hirahata M, Osaki M, Kanda Y, et al. PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma. Cancer Med 2016; 5(5): 892-902.
[http://dx.doi.org/10.1002/cam4.651] [PMID: 26817521]
[13]
Li T, Le A. Glutamine metabolism in cancer. Adv Exp Med Biol 2018; 1063: 13-32.
[http://dx.doi.org/10.1007/978-3-319-77736-8_2] [PMID: 29946773]
[14]
Altman BJ, Stine ZE, Dang CV. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer 2016; 16(10): 619-34.
[http://dx.doi.org/10.1038/nrc.2016.71] [PMID: 27492215]
[15]
Obrist F, Michels J, Durand S, et al. Metabolic vulnerability of cisplatin-resistant cancers. EMBO J 2018; 37(14): e98597.
[http://dx.doi.org/10.15252/embj.201798597] [PMID: 29875130]

Rights & Permissions Print Cite
Article Metrics
13
© 2024 Bentham Science Publishers | Privacy Policy