Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes.
Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes.
复制标题
DOI：
10.18632/oncotarget.15647
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Ishikawa Y
中科院分区：
文献类型：
--
作者：
Inamura K;Yokouchi Y;Kobayashi M;Ninomiya H;Sakakibara R;Subat S;Nagano H;Nomura K;Okumura S;Shibutani T;Ishikawa Y
TROP2是一种跨膜糖蛋白，在多种癌症中过表达。新出现的证据表明，TROP2靶向治疗在既往多次治疗的患者中是有效和安全的。TROP2是治疗肺癌的一个有前景的靶点；然而，关于TROP2的表达与肺癌的临床病理/分子特征，包括预后之间的关系，人们知之甚少。我们用免疫组织化学方法检测了连续的腺癌、鳞状细胞癌(SqCC)和高级别神经内分泌肿瘤(HGNET)中TROP2的膜表达。TROP2在腺癌、SqCCs和HGNETs中的高表达分别为75.0%(17/270)、75%(150/201)和18%(21/115)。有趣的是，TROP2的表达与死亡率的关系取决于肺癌亚型。TROP2的高表达与腺癌较高的肺癌特异性死亡率相关[单变量风险比(HR)=1.6 0，95%可信区间(CI)=1.0 7~2.44，P=0.022]，但与SqCC无关(单变量风险比(HR)=0.79，95%CI=0.35~1.94，P=0.79)。在HGNET中，TROP2的高表达在单变量和多变量分析中均与较低的肺癌特异性死亡率相关(多变量HR=0.13，95%CI=0.020-0.44，P=0.0003)。我们的结果提示TROP2在不同肺癌亚型中的作用不同。
TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with multiple prior treatments. TROP2 is a promising target for lung cancer treatment; however, little is known regarding the association of TROP2 expression with clinicopathological/molecular features, including prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma, squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for the membranous expression of TROP2 using immunohistochemistry. High TROP2 expression was observed in 64% (172/270) of adenocarcinomas, 75% (150/201) of SqCCs, and 18% (21/115) of HGNETs. Intriguingly, the association of TROP2 expression with mortality was dependent on the lung cancer subtype. High TROP2 expression was associated with higher lung cancer-specific mortality in adenocarcinomas [univariable hazard ratio (HR) = 1.60, 95% confidence interval (CI) = 1.07–2.44, P = 0.022)], but not in SqCCs (univariable HR = 0.79, 95% CI = 0.35–1.94, P = 0.79). In HGNETs, high TROP2 expression was associated with lower lung cancer-specific mortality in both univariable and multivariable analyses (multivariable HR = 0.13, 95% CI = 0.020–0.44, P = 0.0003). Our results suggest a differential role for TROP2 in different lung cancer subtypes.