<p>IHC image-4.</p>

Background PTPRCAP (protein tyrosine phosphatase receptor C-associated protein) has been implicated in tumor suppression in several malignancies; however, its role in lung adenocarcinoma (LUAD) remains unclear. This study aimed to investigate the expression profile and functional significance of PTPRCAP in LUAD. Methods Forty-five pairs of LUAD and adjacent non-tumor tissues were collected from patients undergoing surgery at Chengde Medical University Affiliated Hospital. PTPRCAP mRNA and protein levels were quantified by RT-qPCR and immunohistochemistry (IHC), respectively, and correlated with clinicopathological features. A549 and H1299 LUAD cell lines and BEAS-2B normal bronchial epithelial cells were used for in vitro assays. PTPRCAP was overexpressed via plasmid transfection (OE group) and compared with vector-transfected controls (Vector group). Functional assays included CCK-8 proliferation, scratch wound healing, Transwell migration/invasion, and Annexin V-PE apoptosis assays. Apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were evaluated by Western blot. The effect of overexpression PTPRCAP on tumor growth was observed through nude mouse xenografts. Results PTPRCAP mRNA and protein levels were significantly lower in LUAD tissues than in adjacent non-tumor tissues (P < 0.05). Low PTPRCAP expression correlated with advanced TNM stage and poor differentiation (P < 0.05). In vitro, PTPRCAP expression was markedly reduced in A549 and H1299 cells compared with BEAS-2B. Overexpression of PTPRCAP significantly suppressed proliferation, migration, and invasion (P < 0.001), and increased apoptosis rates in both cell lines (P < 0.01). Mechanistically, PTPRCAP upregulation elevated pro-apoptotic Bax and cleaved caspase-3 while downregulating anti-apoptotic Bcl-2 (P < 0.05). In vivo xenograft experiments demonstrated that overexpression PTPRCAP inhibited tumor growth in nude mice (P < 0.001). Conclusions PTPRCAP is downregulated in LUAD and acts as a tumor suppressor by promoting apoptosis and inhibiting proliferation, migration, and invasion. These findings suggest PTPRCAP as a potential therapeutic target for LUAD.背景：蛋白酪氨酸磷酸酶受体C相关蛋白（protein tyrosine phosphatase receptor C-associated protein，PTPRCAP）已被证实可在多种恶性肿瘤中发挥抑癌作用，但其在肺腺癌（lung adenocarcinoma，LUAD）中的作用仍不明确。本研究旨在探讨PTPRCAP在LUAD中的表达谱及其功能意义。 方法：本研究收集了承德医学院附属医院手术患者的45对LUAD组织及配对癌旁正常组织。分别采用逆转录实时定量聚合酶链反应（reverse transcription quantitative PCR，RT-qPCR）和免疫组织化学（immunohistochemistry，IHC）检测PTPRCAP的mRNA和蛋白表达水平，并分析其与临床病理特征的相关性。选用A549、H1299两种LUAD细胞系及BEAS-2B正常支气管上皮细胞开展体外实验。通过质粒转染法过表达PTPRCAP（过表达组），以空质粒转染细胞作为对照组（Vector组）。功能实验包括CCK-8增殖实验、划痕愈合实验、Transwell迁移/侵袭实验以及膜联蛋白V-藻红蛋白（Annexin V-PE）凋亡检测。采用蛋白质印迹法（Western blot）检测凋亡相关蛋白Bax、Bcl-2及剪切型caspase-3的表达水平。通过裸鼠异种移植瘤模型观察过表达PTPRCAP对肿瘤生长的影响。 结果：LUAD组织中PTPRCAP的mRNA及蛋白表达水平均显著低于癌旁正常组织（P<0.05）。PTPRCAP低表达与晚期TNM分期及分化程度差显著相关（P<0.05）。体外实验中，A549及H1299细胞内PTPRCAP的表达水平显著低于BEAS-2B细胞。过表达PTPRCAP可显著抑制两种细胞系的增殖、迁移及侵袭能力（P<0.001），并提高细胞凋亡率（P<0.01）。机制研究显示，PTPRCAP上调可促进促凋亡蛋白Bax及剪切型caspase-3的表达，同时抑制抗凋亡蛋白Bcl-2的表达（P<0.05）。体内异种移植瘤实验证实，过表达PTPRCAP可显著抑制裸鼠体内的肿瘤生长（P<0.001）。 结论：PTPRCAP在LUAD中呈低表达状态，可通过促进细胞凋亡、抑制增殖、迁移及侵袭发挥抑癌作用。上述研究结果提示PTPRCAP可作为LUAD潜在的治疗靶点。