Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Abstract

Purpose Thrombospondin 1 ( THBS1 ) is an endogenous inhibitor of angiogenesis, but it also promotes tumor invasion, metastasis, and immune response in the tumor environment. Previous research has found that THBS1 is highly expressed in many tumors and has a negative correlation with tumor prognosis. However, research on the relationship between THBS1 and immune infiltration in GC is less well documented, and the objective of our study was to investigate the role of THBS1 expression in GC. Patients and Methods The expression of THBS1 in GC was analyzed by Oncomine, TIMER, TGCA, GEO and IHC staining. Analysis of the signaling pathways associated with THBS1 expression in GC uses GSEA. The relationship between THBS1 expression and immune infiltration was analyzed by the ESTIMATE algorithm, single-cell transcriptome analysis, TIMER2 database and CIBERSORT algorithm. Finally, the relationship between THBS1 expression and drug sensitivity was analyzed by the CellMiner database. Results THBS1 was overexpressed in GC and was associated with poor prognosis, and high THBS1 expression was an independent risk factor. GSEA results showed that high THBS1 expression in GC was associated with tumorigenesis, adhesion, and significant immune enrichment. THBS1 expression was most strongly correlated with tumor-associated macrophages (TAMs), M2 macrophages and cancer-associated fibroblast (CAFs) in GC. THBS1 expression positively correlates with most immune checkpoint members, suggesting that THBS1 may play an important role in the tumor microenvironment. THBS1 overexpression was negatively correlated with some drug sensitivities, such as Oxaliplatin. Conclusion Upregulation of THBS1 was positively correlated with poor prognosis and immunosuppression in GC and negatively correlated with anticancer drug sensitivity, suggesting that THBS1 may serve as a potential target for the treatment of GC.

EXTL3 could serve as a potential biomarker of prognosis and immunotherapy for prostate cancer and its potential mechanisms

“…Based on our results, MSI was significantly related to EXTL3 expression in TCGA-PRAD, while TMB and TNB did not have significant associations with EXTL3 expression. To further seek EXTL3-related drugs in PCa, CellMiner database was utilized and this database was designed for facilitating the study and selection of anticancer drugs [ 45 , 46 ]. Our results showed that EXTL3 expression was negatively correlated with AFP464, AP-26113, dexrazoxane, LDK-378, palbociclib, having the potential to prevent the progress of PCa.…”

Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers

“…Over-expression of these proteins has been extensively implicated in a variety of malignancies’ progression and metastasis. ITGB1, FBN1, and THBS1 have not been coherently identified as putative “pan-cancer” early detection biomarkers because a similar study to this one has not been conducted previously [ 109 , 110 , 111 , 112 , 113 , 114 ]. Nonetheless, the notion of other pancancer biomarkers in prognostic detection has already been tested with promising results as highlighted in the DETECT-A clinical trial [ 115 , 116 ].…”

Identification of Potential Novel Prognosis-Related Genes Through Transcriptome Sequencing, Bioinformatics Analysis, and Clinical Validation in Acute Myeloid Leukemia

“…THBS1 was the first member of the THBS to be identified and is thought to be an endogenous inhibitor of angiogenesis (Jeanne et al, 2015). Previous studies have shown that THBS1 is highly expressed in various tumors (Jayachandran et al, 2014;Pal et al, 2016;Kamijo et al, 2020;Zhang et al, 2021). Furthermore, Lidan et al have found that THBS1 was lowly expressed in AML patients, which may be induced by promoter methylation, and patients with low THBS1 expression had a shorter survival time; furthermore, Allogeneic Hematopoietic Stem Cell transplantation can overcome the adverse effects mediated by low THBS1 expression (Zhu et al, 2019).…”