KLK5在甲状腺癌中的表达及相关性分析

Expression and Clinical Relevance of KLK5 in Thyroid Cancer

摘要: 目的：探讨KLK5 (kallikrein like gene 2)在甲状腺癌(Thyroid Cancer, TC)中的表达特征及其与预后的关系。方法：收集2023年9月至2024年9月内蒙古自治区人民医院90例接受手术切除的甲状腺癌患者癌组织及配对癌旁正常组织标本。采用免疫组织化学检测甲状腺癌组织及癌旁正常组织中KLK5的表达情况及其临床病理特征之间的关系；采用TCGA、UCSC Xena、TNMPlot、GEPIA、TISIDB等公共数据库，分析KLK5表达、临床分期、生存预后及免疫微环境的关系。结果：免疫组化结果显示KLK5在甲状腺癌癌组织显著高于癌旁正常组织，差异有统计学意义(P < 0.05)。同时，肿瘤直径 > 1 cm甲状腺癌患者的KLK5阳性率显著高于直径 ≤ 1 cm患者(P < 0.05)。在淋巴结转移方面，有淋巴结转移的患者，其KLK5阳性率明显高于无淋巴结转移的患者，差异有统计学意义(P < 0.05)。通过TCGA数据库分析发现KLK5显著上调并与不良预后相关(P < 0.05)。并与M2巨噬细胞、肥大细胞正相关，与CD8+T细胞、浆细胞负相关(P < 0.05)。结论：KLK5在甲状腺癌中高表达，并与预后不良及免疫微环境调节相关，有望成为甲状腺癌的潜在分子标志物和治疗靶点。

Abstract: Objective: To delineate the expression profile of kallikrein-like peptidase 5 (KLK5) in thyroid cancer (TC) and to evaluate its prognostic significance. Methods: Ninety paired TC and adjacent normal tissue samples collected between September 2023 and September 2024 at the Inner Mongolia Autonomous Region People’s Hospital were analyzed by immunohistochemistry (IHC) for KLK5 expression and its association with clinicopathological parameters. Public repositories (TCGA, UCSC Xena, TNMplot, GEPIA and TISIDB) were mined to correlate KLK5 levels with tumor stage, survival outcomes and immune microenvironment signatures. Results: IHC revealed markedly higher KLK5 expression in TC tissues than in matched normal counterparts (P < 0.05). KLK5 positivity was significantly more frequent in tumors > 1 cm versus ≤ 1 cm (P < 0.05) and in patients with lymph-node metastasis versus those without (P < 0.05). TCGA data confirmed KLK5 up-regulation and showed that high KLK5 expression predicted poor prognosis (P < 0.05). Bioinformatic analyses further demonstrated positive correlations between KLK5 and M2 macrophage as well as mast-cell infiltration, and negative correlations with CD8T-cell and plasma-cell abundance (all P < 0.05). Conclusion: KLK5 is overexpressed in thyroid cancer, associates with adverse clinicopathological features and unfavorable prognosis, and may shape an immunosuppressive microenvironment. KLK5 represents a potential biomarker and therapeutic target for TC.