SKAP1 Is a Novel Biomarker and Therapeutic Target for Gastric Cancer: Evidence from Expression, Functional, and Bioinformatic Analyses

Author:

Zhu Lingqin1,Yu Qiongfang1,Li Yuanheng2,Zhang Meng3,Peng Zhiwei3,Wang Song1,Quan Ziyi3,Gao Dian3ORCID

Affiliation:

1. Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

2. Queen Mary School, Nanchang University, Nanchang 330031, China

3. Department of Pathogen Biology and Immunology, Medical College of Nanchang University, Nanchang 330006, China

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Due to the lack of early symptoms, GC is often diagnosed at an advanced stage when treatment options are limited. There is an urgent need to identify biomarkers for early detection, prognosis evaluation, and targeted treatment of GC. Studies have shown that Src kinase-associated phosphoprotein 1 (SKAP1) promotes cell proliferation and invasion and is associated with poor prognosis in colorectal cancer, malignant fibrous histiocytoma, and breast cancer. However, the role and mechanism of SKAP1 in GC are unclear. Here, analyses of multiple databases and experiments revealed that SKAP1 expression was higher in GC than in adjacent normal tissues. The Cancer Genome Atlas data showed that high SKAP1 expression was associated with poor GC prognosis. SKAP1 expression was higher in GC than in normal gastric epithelial cells. SKAP1 silencing reduced the proliferation, migration and invasion of the GC cell lines MKN45 and HGC27. Rescue experiments suggest that SKAP1 may promote GC progression by activating JAK1/PI3K/AKT signaling and regulating GC cell proliferation, invasion, migration, and other functions. Bioinformatics analysis revealed that SKAP1 was associated with immune cell infiltration and checkpoint expression in GC. High SKAP1 expression was associated with poorer immunotherapy outcomes, suggesting its potential as a predictive biomarker of GC immunotherapy efficacy. In summary, SKAP1 is overexpressed in GC, where it promotes cell proliferation, invasion and migration and is associated with poor prognosis and poor immunotherapy outcomes. SKAP1 may represent a biomarker and therapeutic target in GC and regulates cellular functions through JAK1/PI3K/AKT signaling.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangxi Province

Nanchang University

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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