In-Depth Examination of TPBG As a New Predictive Indicator for Gastric Cancer.

Lianlei Yang,Chunyan Weng,Yaping Zhang, Yu Zhao,Kexin Chen, Guodong Li,Xueqing Zhong,Chenghai He

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE（2025）

First Peoples Hosp Linping Dist | Zhejiang Chinese Med Univ | Hangzhou Normal Univ

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Abstract

Trophoblast glycoprotein (TPBG) plays a significant part in the growth of specific cancers, yet its connection to gastric cancer (GC) remains uncertain. This research seeks to analyse the fluctuation in TPBG levels in GC and evaluate how TPBG expression relates to the prognosis of GC patients. TPBG expression in GC and normal gastric tissues was investigated in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, further extracting the immunohistochemistry images from HPA database and validating by Western blot. The connection between TPBG and GC patients' survival rates was investigated by Kaplan-Meier and COX regression analysis. Genes related to TPBG were enriched using GO and KEGG data. In vitro and in vivo tumour models were utilised to evaluate the function of TPBG in GC. Western blot analysis was performed to detect the expression of PI3K/AKT signalling pathway proteins following TPBG knockdown. Immune infiltration was analysed using the CIBERSOFT and ssGSEA methods. The association between TPBG and immune cells that infiltrate tumours was evaluated through the utilisation of GSVA. TPBG expression increased in several tumour tissues (including GC) more than in adjacent noncancerous tissues. Elevated TPBG level predicted worse outcomes, such as poorer overall survival, pathological stage, and therapy response in GC. Enrichment analysis primarily focused on biological processes like the organisation of external encapsulating structures, extracellular structure, and collagen metabolism. Biological experiments further demonstrated that TPBG knockdown successfully inhibits the progression, migration, and invasion of GC cells. Western blot analysis revealed that TPBG knockdown inhibits the PI3K/AKT signalling pathway. Furthermore, TPBG is associated with the infiltration of immune cells in GC, which correlates with the expression of macrophage cells. There is a positive relationship between TPBG and malignant behaviour of GC tissues and cells, suggesting that TPBG can be useful for diagnosing and prognosing GC.

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Key words

biomarker,gastric cancer,immune infiltration,PI3K/AKT signalling pathway,prognosis,TPBG

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