Ying Lisha, Zhang Fanrong, Pan Xiaodan, Chen Kaiyan, Zhang Nan, Jin Jiaoyue, Wu Junzhou, Feng Jianguo, Yu Herbert, Jin Hongchuan, Su Dan
Laboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Cancer Research Institute, Zhejiang Cancer Hospital & Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province, Hangzhou, China.
Oncotarget. 2016 Dec 27;7(52):86536-86546. doi: 10.18632/oncotarget.13294.
Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected. The expression of C7 was analyzed using reverse transcriptase quantitative polymerase chain reaction. As a result, the C7 expression displayed a gradual downward trend in normal, benign, borderline and malignant ovarian tissues, and the decreased expression of C7 was correlative to poor differentiation in patients with ovarian cancer. Interestingly, a similar change of expression of C7 was found in normal, adjacent and malignant tissues in patients with NSCLC, and low expression of C7 was associated with worse grade and advanced clinical stage. Both results from this cohort and the public database indicated that NSCLC patients with low expression of C7 had a worse outcome. Furthermore, multivariate cox regression analysis showed NSCLC patients with low C7 had a 3.09 or 5.65-fold higher risk for relapse or death than those with high C7 respectively, suggesting C7 was an independent prognostic predictor for prognoses of patients with NSCLC. Additionally, overexpression of C7 inhibited colony formation of NSCLC cells, which hints C7 might be a potential tumor suppressor.
我们之前的研究发现,染色体片段5p13.1 - 13.3的拷贝数变异可能与卵巢癌的进展有关。在本研究中,验证了这种改变,并鉴定出位于5p13.1上的补体成分7(C7)。为了进一步探讨C7在肿瘤中的临床价值,我们收集了浙江肿瘤医院组织库中的156例恶性、22例交界性、33例良性和24例正常卵巢组织,以及173例非小细胞肺癌(NSCLC)组织及其相应的癌旁组织和正常组织。采用逆转录定量聚合酶链反应分析C7的表达。结果显示,C7在正常、良性、交界性和恶性卵巢组织中的表达呈逐渐下降趋势,且C7表达降低与卵巢癌患者的低分化相关。有趣的是,在NSCLC患者的正常、癌旁和恶性组织中也发现了类似的C7表达变化,C7低表达与更差的分级和晚期临床分期相关。本队列研究结果和公共数据库均表明,C7低表达的NSCLC患者预后较差。此外,多因素cox回归分析显示,C7低表达的NSCLC患者复发或死亡风险分别比C7高表达者高3.09倍或5.65倍,提示C7是NSCLC患者预后的独立预测指标。此外,C7过表达抑制NSCLC细胞的集落形成,这提示C7可能是一种潜在的肿瘤抑制因子。