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

Lirui Dai; Yongjie Han; Zhuo Yang; Yuling Zeng; Wulong Liang; Zimin Shi; Yiran Tao; Xianyin Liang; Wanqing Liu; Shaolong Zhou; Zhe Xing; Weihua Hu; Xinjun Wang

doi:10.1111/jcmm.17807

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

J Cell Mol Med. 2023 Aug;27(15):2194-2214. doi: 10.1111/jcmm.17807. Epub 2023 Jun 14.

Authors

Lirui Dai^{1

2

3}, Yongjie Han^{1

3}, Zhuo Yang^{1

3}, Yuling Zeng⁴, Wulong Liang^{1

3}, Zimin Shi^{1

2

3}, Yiran Tao^{1

2

3}, Xianyin Liang^{1

2

3}, Wanqing Liu^{1

2

3}, Shaolong Zhou^{1

3}, Zhe Xing^{1

2

3}, Weihua Hu^{1

3}, Xinjun Wang^{1

2

3}

Affiliations

¹ Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
² Institute of Neuroscience, Zhengzhou University, Zhengzhou, China.
³ Henan International Joint Laboratory of Glioma Metabolism and Microenvironment Research, Zhengzhou, China.
⁴ Department of Blood Transfusion, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Suppressor of cytokine signalling (SOCS) 1/2/3/4 are involved in the occurrence and progression of multiple malignancies; however, their prognostic and developmental value in patients with glioblastoma (GBM) remains unclear. The present study used TCGA, ONCOMINE, SangerBox3.0, UALCAN, TIMER2.0, GENEMANIA, TISDB, The Human Protein Atlas (HPA) and other databases to analyse the expression profile, clinical value and prognosis of SOCS1/2/3/4 in GBM, and to explore the potential development mechanism of action of SOCS1/2/3/4 in GBM. The majority of analyses showed that SOCS1/2/3/4 transcription and translation levels in GBM tissues were significantly higher than those in normal tissues. qRT-PCR, western blotting (WB) and immunohistochemical staining were used to verify that SOCS3 was expressed at higher mRNA and protein levels in GBM than in normal tissues or cells. High SOCS1/2/3/4 mRNA expression was associated with poor prognosis in patients with GBM, especially SOCS3. SOCS1/2/3/4 were highly contraindicated, which had few mutations, and were not associated with clinical prognosis. Furthermore, SOCS1/2/3/4 were associated with the infiltration of specific immune cell types. In addition, SOCS3 may affect the prognosis of patients with GBM through JAK/STAT signalling pathway. Analysis of the GBM-specific protein interaction (PPI) network showed that SOCS1/2/3/4 were involved in multiple potential carcinogenic mechanisms of GBM. In addition, colony formation, Transwell, wound healing and western blotting assays revealed that inhibition of SOCS3 decreased the proliferation, migration and invasion of GBM cells. In conclusion, the present study elucidated the expression profile and prognostic value of SOCS1/2/3/4 in GBM, which may provide potential prognostic biomarkers and therapeutic targets for GBM, especially SOCS3.

Keywords: JAK/STAT3; SOCS1/2/3/4; biomarkers; gene expression profiling; glioblastoma; immune infiltration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Glioblastoma* / genetics
Glioblastoma* / pathology
Humans
Prognosis
RNA, Messenger / metabolism
Suppressor of Cytokine Signaling 1 Protein / metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / genetics
Suppressor of Cytokine Signaling Proteins / metabolism

Substances

Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
RNA, Messenger
Biomarkers
SOCS1 protein, human