Prognostic model based on circular RNA circPDK1 for resected lung squamous cell carcinoma

Xiao Sun; Maolong Wang; Rongjian Xu; Dongyang Zhang; Ao Liu; Yuanyong Wang; Tong Lu; Yanlu Xin; Yandong Zhao; Yunpeng Xuan; Tong Qiu; Hao Wang; Shicheng Li; Yang Wo; Dahai Liu; Jinpeng Zhao; Bo Fu; Yaliang Lan; Yudong Han; Wenjie Jiao

doi:10.21037/tlcr.2019.11.20

Prognostic model based on circular RNA circPDK1 for resected lung squamous cell carcinoma

Transl Lung Cancer Res. 2019 Dec;8(6):907-919. doi: 10.21037/tlcr.2019.11.20.

Authors

Xiao Sun¹, Maolong Wang¹, Rongjian Xu¹, Dongyang Zhang¹, Ao Liu¹, Yuanyong Wang¹, Tong Lu¹, Yanlu Xin², Yandong Zhao¹, Yunpeng Xuan¹, Tong Qiu¹, Hao Wang³, Shicheng Li¹, Yang Wo¹, Dahai Liu⁴, Jinpeng Zhao⁵, Bo Fu⁶, Yaliang Lan¹, Yudong Han¹, Wenjie Jiao¹

Affiliations

¹ Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
² Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
³ Administrative Office, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
⁴ Medical Examination Center, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
⁵ Department of Thoracic Surgery, Laiyang Central Hospital, Yantai 264000, China.
⁶ Otorhinolaryngology Head and Neck Surgery, Affiliated Qilu Hospital of Shandong University, Jinan 250000, China.

Abstract

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^low 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^high 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.

Keywords: Circular RNA; lung squamous cell carcinoma (LSCC); nomograms; prognostic model.