Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer.
Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer.
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DOI：
10.18632/oncotarget.17895
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Kim YH
中科院分区：
文献类型：
--
作者：
Tsuji T;Sakamori Y;Ozasa H;Yagi Y;Ajimizu H;Yasuda Y;Funazo T;Nomizo T;Yoshida H;Nagai H;Maeno K;Oguri T;Hirai T;Kim YH
通过肝细胞生长因子 (HGF) 激活 c-MET 会增加肿瘤发生、诱导耐药性，并与各种实体瘤的不良预后相关。然而，血清HGF（sHGF）对于晚期非小细胞肺癌（NSCLC）患者，尤其是接受细胞毒性化疗的患者的临床价值仍不清楚。在这里，我们表明 sHGF 可能有助于预测晚期 NSCLC 患者的肿瘤反应和无进展生存期 (PFS)。总共对 81 名 NSCLC 患者进行了研究。使用 ELISA 在 4 个时间点评估 sHGF 水平：治疗前、反应评估时（治疗开始后 1-2 个月）、最佳肿瘤反应时和疾病进展时。作为对照生物标志物，CEA 也在肺腺癌中进行了评估。在一线治疗（中位数，153.5 vs. 288.0；P < 0.05）和二线治疗（87.0 vs. 219.5；P = 0.01）中，反应评估时的阳性 sHGF 预测 PFS 较差。在 55 名接受细胞毒性化疗的患者中，多个 Cox 比例风险模型显示，反应评估时不良 PFS 与阳性 sHGF 之间存在显着的独立关联（风险比，4.24；95% CI，2.05 至 9.46；P < 0.01）。肺腺癌亚组分析显示，在接受第二次细胞毒化疗的患者中，低CEA患者与高CEA患者的PFS无显着差异，但治疗前或疗效评估时sHGF阳性预测PFS较差（分别为35.0 vs. 132.0；P < 0.01、50.0 vs. 215.0；P < 0.01）。这些发现为未来研究 sHGF 作为评估 HGF/c-MET 活性的潜在临床生物标志物的优点提供了理论基础，这将有助于指示 c-MET 抑制剂的施用。
Activation of c-MET through hepatocyte growth factor (HGF) increases tumorigenesis, induces resistance, and is associated with poor prognosis in various solid tumors. However, the clinical value of serum HGF (sHGF) in patients with advanced non-small cell lung cancer (NSCLC), especially those receiving cytotoxic chemotherapy, remains unknown. Here, we show that sHGF may be useful to predict tumor response and progression-free survival (PFS) in patients with advanced NSCLC. A total of 81 patients with NSCLC were investigated. sHGF levels were evaluated using ELISA at 4 time-points: at pre-treatment, at response-evaluation (1–2 months after treatment initiation), at the best tumor response, and at disease progression. As a control biomarker, CEA was also evaluated in lung adenocarcinoma. Positive-sHGF at response-evaluation predicted poor PFS compared with Negative-sHGF in both first-line (median, 153.5 vs. 288.0; P < 0.05) and second-line treatment (87.0 vs. 219.5; P = 0.01). In 55 patients that received cytotoxic chemotherapy, multiple Cox proportional hazards models showed significant independent associations between poor PFS and Positive-sHGF at response-evaluation (hazard ratio, 4.24; 95% CI, 2.05 to 9.46; P < 0.01). Lung adenocarcinoma subgroup analysis showed that in patients receiving second cytotoxic chemotherapy, there were no significant differences in PFS between patients with low-CEA compared with those with high-CEA, but Positive-sHGF at pre-treatment or at response-evaluation predicted poor PFS (35.0 vs. 132.0; P < 0.01, 50.0 vs. 215.0; P < 0.01, respectively). These findings give a rationale for future research investigating the merit of sHGF as a potential clinical biomarker to evaluate HGF/c-MET activity, which would be useful to indicate administration of c-MET inhibitors.
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作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
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