SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer.

Jinwen Yin,Hao Wang,Qiu Zhao,Lan Liu,Congqing Jiang,Anli Ren,Yuntian Hong,Haizhou Wang,Mengting Li

doi:10.3389/fcell.2021.795133

Abstract

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

Highlights

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer, causing more than ninety thousand deaths worldwide every year (Bray et al, 2018; Siegel et al, 2020)
The SCG2 expression levels were higher in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), head and neck cancer (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung squamous cell carcinoma (LUSC) compared with adjacent normal tissues
SCG2 expression was significantly lower in colon adenocarcinoma (COAD), kidney chromophobe (KICH), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC) compared with adjacent normal tissues (Figure 1A)

Summary

Introduction

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer, causing more than ninety thousand deaths worldwide every year (Bray et al, 2018; Siegel et al, 2020). Diagnosis and treatment have been improved substantially, the prognosis of patients remains poor, especially in those with higher TNM stage (Luebeck et al, 2013; Miller et al, 20162016). Abnormal expression of multiple genes is usually associated with the occurrence of CRC (Meyerson et al, 2010). The molecular mechanisms underlying CRC remain unclear. New treatment modalities have been proposed for CRC, such as immunotherapy (Overman et al, 2018). Studies have shown that the tumor microenvironment (TME) significantly affects CRC progression and therapeutic efficacy (Halama et al, 2011). Monoclonal antibodies against programmed cell death 1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) have been proven effective in clinical trials (Rotte, 2019)

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