背景与目的:甲状旁腺激素相关蛋白(paratlayroid hormone-related protein,PTHrP)通常在非小细胞肺癌(non-small cell lung cancer,NSCLC)中表达,结构与甲状旁腺激素(parathyroid hormone,PTH)相似,除引起恶性肿瘤高钙血症,还可调节癌细胞的生长、凋亡和肿瘤血管生成,此作用与性激素状态相关.本研究旨在探讨NSCLC患者中PTHrP的表达、PTHrP的表达与性别的关系及其临床意义,为肺癌发病过程中性别角色的研究提供一定的临床依据.方法:用免疫组织化学SP法检测125例NSCLC肿瘤组织、癌旁组织及远端正常组织中PTHrP的表达,分析PTHrP的表达与患者年龄、性别、组织学分型、临床分期、吸烟史及预后的相关性.用Log-rank法比较阳性及阴性患者的生存率.结果:NSCLC肿瘤组织、癌旁组织及远端正常组织中PTHrP的阳性表达率分别是65.6%(82/125)、24%(30/125)和16.8%(21/125),在癌组织中的表达较在癌旁组织和正常对照组织中的表达高(P<0.05).在女性患者中PTHrP的表达(82.7%)较在男性患者中PTHrP的表达(53.4%)高(P<0.05).在不同的组织学分型中以腺癌PTHrP的表达高(70.8%),但差异无统计学意义(P=0.359).女性患者中PTHrP阳性者的中位生存时间是38.62个月,PTHrP阴性者的中位生存时间是20.00个月(P<0.05);男性患者中PTHrP阳性者的中位生存时间是27.14个月,PTHrP阴性者的中位生存时间是25.00个月(P>0.05).在吸烟者中,PTHrP阳性者的中位生存时间是35.24个月,PTHrP阴性者的中位生存时间是25.00个月(P<0.05);不吸烟者中,PTHrP阳性者的中位生存时间是38.71个月,PTHrP阴性者的中位生存时间是20.00个月(P<0.05).结论:在NscLc患者中PTHrP的表达在肿瘤组织中较高,在女性患者中较高,在腺癌中相对较高.女性患者的生存状态与PTHrP的表达有关,PTHrP阳性者的生存率更高;男性患者的生存状态与PTHrP的表达无关.吸烟或不吸烟者的生存状态均与PTHrP的表达有关,PTHrP阳性者的生存率更高.PTHrP的表达可能和女性患者的生存优势有关,在控制了年龄、分期及组织学的影响以后,对女性患者的生存率而言,PTHrP可能是一个有意义的预测指标.%Background and purpose: Parathyroid hormone-related protein (PTHrP) is commonly expressed in non-small cell lung cancer (NSCLC). PTHrP shares structural similarities with PTH. It duplicates the effects of PTH 1-34 in tissues that bear the receptor, including causing hypercalcemia. It regulates cancer cell growth, apoptosis, and angiogenesis. This kind of effects of PTHrP is gender-dependent in lung cancer. This study examined the expression of PTHrP, the relationship between PTHrP expression and gender, clinical significance in patients with non-small cell lung cancer. This research can provide some clinical basis for the relationship between lung cancer progression and gender roles. Methods: PTHrP expression was assessed in paraffin-embedded tumor tissues, non-cancerous adjacent lung tissues, normal lung tissues from 125 patients with NSCLC by immunohistochemistry. We analyzed the relationship between PTHrP expression and age, gender, histological differentiation, clinical stage, smoking and prognosis. The Logrank test was used to compare survivals of PTHrP-positive with that of PTHrP-negative groups. Results: The positive rate of PTHrP expression in tumor tissues, non-cancerous adjacent lung tissues, normal lung tissues were 65.6％ (82/125),24％(30/125) and 16.8％(21 / 125), respectively. The PTHrP expression of tumor tissues was significantly higher than that of non-cancerous adjacent lung tissues, normal lung tissues (P＜0.05). The PTHrP expression in female patients (82.7％) was higher than that in male patients (53.4％, P＜0.05). The high expression of PTHrP was in adenocarcinoma (70.8％, P=0.359). Median survival was 38.62 vs 20.00 months (P＜0.05) in female patients with and without tumor PTHrP, respectively, 27.14 vs 25.00 months (P＞0.05) in male patients with and without tumor PTHrP, respectively,35.24 vs 25.00 months (P＜0.05) in smokers with and without tumor PTHrP, respectively, 38.71 vs 20.00 months(P＜0.05) in nonsmokers with and without tumor PTHrP, respectively. Conclusion: In non-small cell lung cancer, the expression of PTHrP was higher in the tumor tissues, female patients and adenocarcinoma. The survival rate was higher in PTHrP positive patients and no correlation with the expression of PTHrP in the male patients. The survival status was associated with the expression of PTHrP either in smokers or in non-smokers than negative patients. The survival rate of PTHrP positive patients was higher than negative patients. The expression of PTHrP was associated with a survival advantage in female patients with NSCLC. PTHrP remained a significant predictor of survival for female patients after controlling for age, stage and histology.
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