基于环状RNA circPDK1的肺鳞状细胞癌切除术后预后模型
Prognostic model based on circular RNA circPDK1 for resected lung squamous cell carcinoma.
作者信息
Sun Xiao, Wang Maolong, Xu Rongjian, Zhang Dongyang, Liu Ao, Wang Yuanyong, Lu Tong, Xin Yanlu, Zhao Yandong, Xuan Yunpeng, Qiu Tong, Wang Hao, Li Shicheng, Wo Yang, Liu Dahai, Zhao Jinpeng, Fu Bo, Lan Yaliang, Han Yudong, Jiao Wenjie
机构信息
Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
出版信息
Transl Lung Cancer Res. 2019 Dec;8(6):907-919. doi: 10.21037/tlcr.2019.11.20.
BACKGROUND
Circular RNA has been revealed as a potential biomarker in multiple malignancies. However, few studies have focused on its potential to be prognostic markers in lung squamous cell carcinoma (LSCC). In this work, we aimed to build a prognostic model of resected LSCC based on circular RNA pyruvate dehydrogenase kinase 1 (circPDK1) and other clinicopathological factors.
METHODS
circPDK1 was identified via next-generation sequencing. Three hundred two cases of LSCC tissue and their adjacent normal lung tissues were obtained from multiple medical centers and divided into study cohort (n=232) and validation cohort (n=70). The expression of circPDK1 was detected for analyzing its potential prognostic value for recurrence-free survival (RFS) and overall survival (OS) in LSCC. Finally, combined with circPDK1, T staging, lymph nodes (LN) metastasis status, age, and serum squamous cell Carcinoma Antigen (SCCAg), we built a prognostic model by nomograms method and confirmed it in the validation cohort.
RESULTS
CircPDK1 was identified to be overexpressed (P<0.01) in LSCC. Through analysis in study cohort, circPDK1 patients (less than the mean expression, n=124) showed more lymph nodes metastasis (P=0.025), more vascular invasion (VI) (P=0.047), more visceral pleural invasion (VPI) (P=0.015) and poorer prognosis (P=0.003) than circPDK1 ones (n=108). Univariate and multivariate analysis showed that circPDK1, T staging, LN status, age, and SCCAg were significant prognostic factors for RFS and OS. The prognostic model based on these factors showed the concordance index (C-index) of 0.8214 and 0.8359 for predicting 5-year RFS and OS, respectively. Finally, the calibration curves were performed in the study cohort and a validation cohort to evaluate the model's efficiency.
CONCLUSIONS
circPDK1 was identified as a potential biomarker of resected LSCC. The prognostic model including circPDK1, T staging, LN status, age, and SCCAg could effectively predict prognosis of resected LSCC.
背景
环状RNA已被揭示为多种恶性肿瘤中的一种潜在生物标志物。然而，很少有研究关注其作为肺鳞状细胞癌（LSCC）预后标志物的潜力。在这项研究中，我们旨在基于环状RNA丙酮酸脱氢酶激酶1（circPDK1）和其他临床病理因素构建一个切除性LSCC的预后模型。
方法
通过下一代测序鉴定circPDK1。从多个医疗中心获取302例LSCC组织及其相邻的正常肺组织，并分为研究队列（n = 232）和验证队列（n = 70）。检测circPDK1的表达，以分析其对LSCC无复发生存期（RFS）和总生存期（OS）的潜在预后价值。最后，结合circPDK1、T分期、淋巴结（LN）转移状态、年龄和血清鳞状细胞癌抗原（SCCAg），我们通过列线图方法构建了一个预后模型，并在验证队列中进行了验证。
结果
在LSCC中鉴定出circPDK1过表达（P < 0.01）。通过在研究队列中的分析，circPDK1表达低于均值的患者（n = 124）比circPDK1表达高于均值的患者（n = 108）表现出更多的淋巴结转移（P = 0.025）、更多的血管侵犯（VI）（P = 0.047）、更多的脏层胸膜侵犯（VPI）（P = 0.015）和更差的预后（P = 0.003）。单因素和多因素分析表明，circPDK1、T分期、LN状态、年龄和SCCAg是RFS和OS的重要预后因素。基于这些因素的预后模型预测5年RFS和OS的一致性指数（C指数）分别为0.8214和0.8359。最后，在研究队列和验证队列中绘制校准曲线以评估模型的有效性。
结论
circPDK1被鉴定为切除性LSCC的一种潜在生物标志物。包括circPDK1、T分期、LN状态、年龄和SCCAg的预后模型可以有效预测切除性LSCC的预后。
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