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

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

doi:10.1186/s12935-019-1041-5

Abstract

BackgroundThis study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients.MethodsA 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.ResultsHere, 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.ConclusionsThese 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.

Highlights

This study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients
Association between Collagen triple helix repeat containing 1 (CTHRC1) expression and tumor angiogenesis markers We found that patients in the CTHRC1High group expressed more vascular endothelial growth factor (VEGF) (P < 0.001; Table 4) and had a higher Microvessel density (MVD) (P = 0.001; Fig. 3a, Table 4) than those in the CTHRC1Low group
The results showed that angiogenesisassociated genes were enriched in the high-CTHRC1 group, which indicated that the expression of genes related to the promotion of angiogenesis was more activated in Lung adenocarcinoma (LUAD) patients with high CTHRC1 levels than in LUAD patients with low CTHRC1 levels

Summary

Introduction

This study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients. According to the most recently reported global cancer statistics, lung cancer remains the leading cause of cancer-related deaths [1,2,3] and the mortality rate is 18.4% [1]. Lung adenocarcinoma (LUAD), the most commonly diagnosed histologic subtype of lung cancer [4], causes more than 500,000 deaths globally each year [5, 6]. According to our previous studies, CTHRC1 overexpression was significantly correlated with metastasis in patients with non-small cell lung cancer (NSCLC) [23]. More evidence still needed to determine the prognostic value of CTHRC1 in LUAD, which is the most common subtype of lung cancer

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