SOCS3 as a potential driver of lung metastasis in colon cancer patients

Xuejie Li; Zuyi Yang; Bi Chen; Lei Gu; Guoyan Tian; Xinbing Sui

doi:10.3389/fimmu.2023.1088542

SOCS3 as a potential driver of lung metastasis in colon cancer patients

Front Immunol. 2023 Mar 21:14:1088542. doi: 10.3389/fimmu.2023.1088542. eCollection 2023.

Authors

Xuejie Li¹, Zuyi Yang², Bi Chen^{3

4}, Lei Gu², Guoyan Tian², Xinbing Sui^{3

4}

Affiliations

¹ Department of Pathology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China.
² Department of Hematology and Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, China.
³ School of Pharmacy, Hangzhou Normal University, Hangzhou, China.
⁴ Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University, Hangzhou, China.

Abstract

Background: The suppressor of cytokine signaling 3 (SOCS3) is the negative feedback regulator of the JAK-STAT signaling pathway. The purpose of our study was to investigate the SOCS3 status in colon primary tumor and lung metastasis and its relationship with macrophages.

Methods: The SOCS3 expression pattern and its relationship with the immune response in pan-cancer was investigated using multiple methods. Samples and corresponding clinical information of 32 colon cancer patients with lung metastasis were collected, and the CD68, CD163, and SOCS3 status were conducted using immunohistochemistry (IHC). The relationship between SOCS3 status and macrophage markers was analyzed. Besides, we explored the molecular mechanisms of SOCS3 in lung metastasis via the TCGA database.

Results: High SOCS3 expression was more inclined to poor prognosis and was positively correlated with main immune cell infiltration in almost each cancer type, especially in colon cancer. Compared with the colon primary tumor, lung metastasis harbored higher CD163 and SOCS3 expression, and high SOCS3 expression was more likely to be associated with high CD163 expression in lung metastasis. Besides, the exceptional differentially expressed genes in lung metastasis significantly enriched in immune responses and regulations.

Conclusions: SOCS3 possessed value as a prognostic marker and target for immunotherapeutic intervention in different tumors and might be a potential target of tumor progression and tumor immunotherapy in colon cancer.

Keywords: SOCS3; colon primary tumor; immune infiltration; lung metastasis; macrophage.

Publication types

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

MeSH terms

Colonic Neoplasms* / genetics
Colonic Neoplasms* / pathology
Humans
Immunohistochemistry
Lung Neoplasms* / genetics
Lung Neoplasms* / secondary
Suppressor of Cytokine Signaling 3 Protein* / genetics
Suppressor of Cytokine Signaling 3 Protein* / metabolism
Suppressor of Cytokine Signaling Proteins / genetics

Substances

SOCS3 protein, human
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins

Grants and funding

This work was supported by the grant from the Science and Technology Development Fund, Macau SAR (No. 0098/2021/A2, to XS) and the Medical Health Science and Technology Project of Hangzhou (No. A20200772, to ZY).