目的：分析甲状旁腺激素样激素（PTHLH）基因与肺鳞状细胞癌（LSCC）患者预后及其与肿瘤微环境（TME）免疫细胞浸润的相关性。方法：通过 UALCAN、TIMER、cBioPortal 数据库在泛癌水平分析 PTHLH 在泛癌中的表达情况，运用 KaplanMeier Plotter数据库分析PTHLH在LSCC中的表达及其与患者的预后关联。选用2017年1月至2020年12月在甘肃省肿瘤医院手术切除的 24 例 LSCC 患者的癌及癌旁组织标本，用 qPCR 和 WB 法分别检测 LSCC 组织中 PTHLH mRNA 和蛋白的表达，用qPCR法检测各种趋化因子和MHC分子的表达水平。采用TIMER数据库联合CIBERSORT反卷积法分析PTHLH基因表达和LSCC的TME中免疫细胞浸润的关系。结果：LSCC组织中PTHLH mRNA和蛋白的表达水平均显著高于癌旁组织（均P<0.05），且PTHLH高表达LSCC患者的OS明显缩短（P<0.01）。PTHLH的表达与LSCC患者TME密切相关（P<0.01）。PTHLH的表达与B细胞、CD8+T细胞、CD4+ T 细胞、中性粒细胞和 DC 等免疫浸润呈显著负相关（r=-0.142、-0.123、-0.224、-0.166、-0.213，均P<0.01）。PTHLH高表达抑制趋化因子、MHC分子的表达，从而抑制炎症反应、免疫浸润、抗肿瘤免疫反应等。PTHLH的表达与免疫检查点分子CTLA-4、PDCD1、TIGIT呈负相关（r=-0.340、-0.441、-0.38，均P<0.01）。结论：PTHLH与肿瘤免疫抑制相关，有望成为预测LSCC患者预后和免疫治疗效果的潜在生物标志物。

Objective: To analyze the association of parathyroid hormone-like hormone (PTHLH) with the prognosis as well as the immune cell infiltration in the tumor microenvironment (TME) of patients with lung squamous cell carcinoma (LSCC). Methods: The expression pattern of PTHLH in pan-cancer was analyzed by UALCAN, TIMER, and cBioPortal databases, and the Kaplan-Meier Plotter database was used to analyze the relationship between the expression of PTHLH in LSCC and the prognosis of patients. The cancer tissues and paracancerous tissues of 24 LSCC patients who underwent surgical resection in the Gansu Cancer Hospital from January 2017 to December 2020 were selected for this study. The mRNA and protein expression levels of PTHLH in LSCC tissues were verified by qPCR and WB, and the expression levels of various chemokines and MHC molecules were detected by qPCR. Then, the correlation between PTHLH expression and immune infiltration in the TME of LSCC was investigated by the TIMER database combined with CIBERSORT deconvolution method.Results: Compared with para-cancerous tissues, the mRNA and protein expression levels of PTHLH were significantly higher in LSCC tissues (both P<0.05). Furthermore, the OS of LSCC patients with high PTHLH expression was significantly shortened (P<0.01). In addition, the expression of PTHLH was closely related to the TME in patients with LSCC (P<0.01). The expression of PTHLH was negatively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils and dendritic cells (r=-0.142, -0.123, -0.224, -0.166,-0.213, all P<0.01). Overexpression of PTHLH inhibited the expression of chemokines and MHC molecules, thereby inhibiting inflammatory responses, immune infiltration, anti-tumor immune responses, etc. Additionally, the expression of PTHLH was negatively correlated with the levels of immune checkpoint molecules CTLA-4, PDCD1 and TIGIT (r=-0.340, -0.441, -0.38, all P<0.01). Conclusion: PTHLH is associated with tumor immunosuppression and is expected to serve as a potential biomarker for predicting immunotherapy effect and prognosis in patients with LSCC.

甘肃省卫生健康行业科研计划项目（No.GSWSKY2020-40）