High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

Yangshan Chen; Yu Sun; Yongmei Cui; Yiyan Lei; Neng Jiang; Wenting Jiang; Han Wang; Lili Chen; Jiping Luo; Yanyang Chen; Kejing Tang; Chengzhi Zhou; Zunfu Ke

doi:10.1186/s12935-019-1041-5

High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

Cancer Cell Int. 2019 Nov 29:19:318. doi: 10.1186/s12935-019-1041-5. eCollection 2019.

Authors

Yangshan Chen^#¹, Yu Sun^#¹, Yongmei Cui¹, Yiyan Lei², Neng Jiang¹, Wenting Jiang¹, Han Wang¹, Lili Chen¹, Jiping Luo¹, Yanyang Chen¹, Kejing Tang³, Chengzhi Zhou⁴, Zunfu Ke^{1

5}

Affiliations

¹ 1Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan Second Road, Guangzhou, 510080 Guangdong People's Republic of China.
² 2Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 Guangdong People's Republic of China.
³ 3Department of Respiratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 Guangdong People's Republic of China.
⁴ 4State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510080 Guangdong People's Republic of China.
⁵ 5Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 Guangdong People's Republic of China.

^# Contributed equally.

Abstract

Background: This study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients.

Methods: A total of 210 LUAD patients diagnosed between 2003 and 2016 in the Department of Pathology of the First Affiliated Hospital of Sun Yat-sen University were included in this study. The expression of CTHRC1 and vascular endothelial growth factor (VEGF), and microvessel density (MVD, determined by CD34 immunostaining) were evaluated by immunohistochemistry in LUAD tissues. The association between the expression of these proteins and clinicopathological features or clinical outcomes was analyzed.

Results: Here, we confirmed that CTHRC1 expression was associated with prognosis and can serve as a significant predictor for overall survival (OS) and progression-free survival (PFS) in LUAD. Additionally, we observed that CTHRC1 expression was positively associated with tumor angiogenesis markers, such as VEGF expression (P < 0.001) and MVD (P < 0.01). Then, we performed gene set enrichment analysis (GESA) and cell experiments to confirm that enhanced CTHRC1 expression can promote VEGF levels. Based on and cox regression analysis, a predictive model that included CTHRC1, VEGF and MVD was constructed and confirmed as a more accurate independent predictor for OS (P = 0.001) and PFS (P < 0.001) in LUAD than other parameters.

Conclusions: These results demonstrated that high CTHRC1 expression may be closely related to tumor angiogenesis and poor prognosis in LUAD. The predictive model based on the CTHRC1 level and tumor angiogenesis markers can be used to predict LUAD patient prognosis more accurately.

Keywords: Collagen triple helix repeat containing 1 (CTHRC1); Lung adenocarcinoma (LUAD); Microvessel density (MVD); Tumor angiogenesis; Vascular endothelial growth factor (VEGF).