Xiang Xueping, Ma Xiaojing, Fang Mao, Zhong Like, Liu Hui, Liu Hong, Tong Yinghui
Department of Pathology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Zhejiang Normal University-Jinhua People's Hospital Joint Center for Biomedical Research, Jinhua 321000, China.
Transl Cancer Res. 2019 Nov;8(7):2535-2542. doi: 10.21037/tcr.2019.10.16.
Platinum-based chemotherapy is the cornerstone of non-small cell lung cancer (NSCLC) therapy. However, the molecular mechanisms and predictive markers of platinum chemoresistance have not been fully understood. Our recent study revealed that Jumonji domain containing 5 (JMJD5) expression in cells was elevated under DNA damage by alkylating agent or UV radiation, which suggests a potential role of JMJD5 in DNA damage related chemoresistance. However, the role of JMJD5 in NSCLC chemotherapy has not been reported. In this study, we demonstrated JMJD5 as a potential prognostic indicator in NSCLC patients who received platinum-based chemotherapy.
JMJD5 protein expression level in tumor and adjacent normal tissues were detected by immunohistochemistry. Samples were from primary NSCLC patients who received platinum-based chemotherapy after surgical resection. Survival curves were presented by the Kaplan-Meier method and p value was acquired by log-rank test. Multivariate analysis was tested by Cox proportional-hazards regression method.
Elevated JMJD5 expression was found in 27.2% cases of tumor tissues (22/81), and high JMJD5 expression were significantly associated with poor overall survival time (OS) [HR =2.881 (1.774-9.121), P=0.001] and progression-free survival time (PFS) [HR =2.255 (1.417-5.886), P=0.004] in NSCLC patients who received platinum-based chemotherapy. In multivariate analyses, JMJD5 was proved to be an independent prognostic indictor for shorter OS [HR =2.339 (1.158-4.724), P=0.018] and PFS [HR =2.031 (1.095-3.767), P=0.025).
High JMJD5 expression indicated a worse prognosis in NSCLC patients who received platinum-based chemotherapy, and JMJD5 may serve as a novel predictive marker in NSCLC chemotherapy.
铂类化疗是非小细胞肺癌(NSCLC)治疗的基石。然而,铂类化疗耐药的分子机制和预测标志物尚未完全明确。我们最近的研究表明,在细胞中,含Jumonji结构域5(JMJD5)的表达在烷基化剂或紫外线辐射导致的DNA损伤下会升高,这提示JMJD5在与DNA损伤相关的化疗耐药中可能发挥作用。然而,JMJD5在NSCLC化疗中的作用尚未见报道。在本研究中,我们证明JMJD5是接受铂类化疗的NSCLC患者的一个潜在预后指标。
采用免疫组织化学法检测肿瘤组织及癌旁正常组织中JMJD5蛋白表达水平。样本来自手术切除后接受铂类化疗的原发性NSCLC患者。生存曲线采用Kaplan-Meier法绘制,P值通过对数秩检验获得。多因素分析采用Cox比例风险回归法进行检验。
在27.2%的肿瘤组织病例(22/81)中发现JMJD5表达升高,在接受铂类化疗的NSCLC患者中,高JMJD5表达与总生存时间(OS)较差显著相关[风险比(HR)=2.881(1.774 - 9.121),P = 0.001]以及无进展生存时间(PFS)较差显著相关[HR = 2.255(1.417 - 5.886),P = 0.004]。在多因素分析中,JMJD5被证明是OS较短[HR = 2.339(1.158 - 4.724),P = 0.018]和PFS较短[HR = 2.031(1.095 - 3.767),P = 0.025]的独立预后指标。
高JMJD5表达表明接受铂类化疗的NSCLC患者预后较差,且JMJD5可能作为NSCLC化疗中的一种新型预测标志物。