{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProstate stem cell antigen (PSCA) is a glycosylphosphatidylinositol‐anchored cell surface protein that is normally expressed in a tissue‐restricted manner – for example in the prostate and gastric epithelium – where it marks a subpopulation of epithelial cells undergoing differentiation and regulated cell‐cycle progression. In normal prostate tissue, PSCA identifies cells transitioning from a basal to a secretory phenotype and is tightly controlled by androgen‐responsive elements, suggesting a role in cellular differentiation and proliferation. In the gastric epithelium, PSCA expression is found in differentiating cells and displays a cell‐proliferation inhibitory activity, and its loss or silencing has been observed in diffuse‐type gastric cancer. Additionally, PSCA is highly expressed on the surface of prostate and other cancer cells – including those of the bladder and pancreas – making it a promising candidate for diagnostic applications and immunotherapeutic targeting."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variations in the PSCA gene have been consistently associated with the risk, phenotype, and prognosis of several cancers. Studies in diverse populations – including Japanese, Korean, Chinese, Tibetan and Caucasian cohorts – have identified single nucleotide polymorphisms (for example, rs2294008 and rs2976392) that affect PSCA promoter activity, mRNA expression levels, and even protein localization. These polymorphisms are linked not only to diffuse‐type gastric cancer, duodenal ulcer, and gallbladder cancer (where PSCA appears to have tumor‐suppressive functions) but also to bladder, prostate, and even breast and colorectal cancers, where overexpression of PSCA is often observed. Together, these findings suggest that allelic variations in PSCA may modulate its tissue‐specific expression and biological activity, thereby influencing susceptibility to cancer and clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as a biomarker, PSCA is emerging as a therapeutic target and a modulator of intracellular signaling and cell‐cycle regulation. Preclinical studies have employed PSCA as a target for chimeric antigen receptor (CAR) T‐cell therapies and monoclonal antibodies in prostate cancer, while experimental systems have elucidated its influence on metastatic behavior – for instance, in nasopharyngeal carcinoma – and its participation in cell cycle control in prostate cancer models. Moreover, recent research has extended the functional landscape of the PSCA locus by identifying a long noncoding RNA (lncPSCA) whose expression is regulated by genetic variants and which, via interactions that promote degradation of key regulatory proteins, activates p53‐dependent signaling pathways. These insights not only expand our understanding of the “Jekyll and Hyde” roles of PSCA – acting either as an oncogene or a tumor suppressor in a context‐dependent manner – but also underscore its potential in precision diagnostics and individualized cancer therapy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tetsuro Watabe, Mark Lin, Hisamitsu Ide, et al. 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