SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

Abstract

The suppressor of cytokine signaling (SOCS) family contains eight members, including SOCS1–7 and CIS, and SOCS3 has been shown to inhibit cytokine signal transduction in various signaling pathways. Although several studies have currently shown the correlations between SOCS3 and several types of cancer, no pan-cancer analysis is available to date. We used various computational tools to explore the expression and pathogenic roles of SOCS3 in several types of cancer, assessing its potential role in the pathogenesis of cancer, in tumor immune infiltration, tumor progression, immune evasion, therapeutic response, and prognostic. The results showed that SOCS3 was downregulated in most The Cancer Genome Atlas (TCGA) cancer datasets but was highly expressed in brain tumors, breast cancer, esophageal cancer, colorectal cancer, and lymphoma. High SOCS3 expression in glioblastoma multiforme (GBM) and brain lower-grade glioma (LGG) were verified through immunohistochemical experiments. GEPIA and Kaplan–Meier Plotter were used, and this bioinformatics analysis showed that high SOCS3 expression was associated with a poor prognosis in the majority of cancers, including LGG and GBM. Our analysis also indicated that SOCS3 may be involved in tumor immune evasion via immune cell infiltration or T-cell exclusion across different types of cancer. In addition, SOCS3 methylation was negatively correlated with mRNA expression levels, worse prognoses, and dysfunctional T-cell phenotypes in various types of cancer. Next, different analytical methods were used to select genes related to SOCS3 gene alterations and carcinogenic characteristics, such as STAT3, SNAI1, NFKBIA, BCL10, TK1, PGS1, BIRC5, TMC8, and AFMID, and several biological functions were identified between them. We found that SOCS3 was involved in cancer development primarily through the JAK/STAT signaling pathway and cytokine receptor activity. Furthermore, SOCS3 expression levels were associated with immunotherapy or chemotherapy for numerous types of cancer. In conclusion, this study showed that SOCS3 is an immune-oncogenic molecule that may possess value as a biomarker for diagnosis, treatment, and prognosis of several types of cancer in the future.

Identification and validation of SOCS1/2/3/4 as potential prognostic biomarkers and correlate with immune infiltration in glioblastoma

“…The current study found that GBM with high SOCS1/2/3/4 expression had a poor prognosis. Our group previously found a potential correlation between SOCS3 expression and GBM 45 . The current study verified the presence of high SOCS3 expression in a variety of cell lines through cell experiments, and the RT‐qPCR and IHC analyses of human tissue specimens demonstrated the high expression of SOCS3 in GBM.…”

“…Our group previously found a potential correlation between SOCS3 expression and GBM. 45 The current study verified the presence of high SOCS3 expression in a variety of cell lines through cell experiments, and the RT-qPCR and IHC analyses of human tissue specimens demonstrated the high expression of SOCS3 in GBM. To further explore the potential role of SOCS3 as a marker for poor prognosis of GBM, SOCS3 was knocked down by siRNA, and it was found that cell lines with reduced SOCS3 expression had lower proliferation levels, and reduced migration and invasion abilities.…”

Pomegranate Peel Extract Sensitizes Hepatocellular Carcinoma Cells to Ionizing Radiation, Induces Apoptosis and Inhibits MAPK, JAK/STAT3, β-Catenin/NOTCH, and SOCS3 Signaling

“…39 In the current investigation, the disparity between proliferation and apoptosis was illustrated by raising the level of SOCS3 and diminishing the level of PPAR-γ and the proapoptotic caspase-3 in HepG2 group (Figure 5). As reported in the study of Dai et al, 40 SOCS3 is an immune-oncogenic molecule that is predominantly implicated in the genesis of tumor mainly via the JAK/STAT signaling transduction pathway and cytokine receptor activation. These findings suggest that SOCS3 is important for the genesis and progression of several malignancies and may serve as an important objective for cancer detection and treatment.…”

Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment

“…For example, Dai et al showed that SOCS3 was useful for the diagnosis, staging, histological subtyping, prognosis, and therapeutic response in several types of cancer in the context of immuno-oncology via multiple mechanisms, and that genetic or epigenetic alterations in SOCS3 frequently predict a poor prognosis. SOCS3 expression and changes in the tumor-cell immune infiltration were predicted through the presence of immunosuppressive cells (MDSCs, CAFs, M2-TAMS, and Tregs) that promote T-cell exclusion [ 65 ]. Therefore, frequent follow-up of more patients co-expressing PDL-1 and SOCS3 could provide future insights.…”