CD155 Overexpression Correlates With Poor Prognosis in Primary Small Cell Carcinoma of the Esophagus.

Kaikai Zhao,Lin Ma,Xiangjiao Meng,Zhaoqin Huang,Lei Feng,Jinming Yu

doi:10.3389/fmolb.2020.608404

Abstract

CD155/TIGIT overexpression has been detected in various human malignancies; however, its expression status in primary small cell carcinoma of the esophagus (PSCCE) and its prognostic significance remain unclear. In this study, we aimed to explore the expression and prognostic value of CD155 and TIGIT in PSCCE. We detected CD155 and TIGIT expression in 114 cases of PSCCE using immunohistochemistry (IHC) and evaluated their relationship with the clinicopathological characteristics and survival of the patients. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. Nomogram performance was assessed via the concordance index (C-index) and calibration plots. Decision curve analysis (DCA) was performed to evaluate the net benefit of the nomogram. We found that CD155 and TIGIT were overexpressed in PSCCE tissues, CD155 expression correlated positively with TIGIT (p < 0.001) and was significantly associated with tumor size, T stage, distant metastasis, TNM stage, and Ki-67 score. TIGIT expression was also significantly associated with T stage, distant metastasis, and TNM stage. Patients with high CD155 and TIGIT expression had a significantly shorter overall survival (OS) and progression-free survival (PFS), while the multivariate model showed that CD155 expression and the therapeutic strategy are independent prognostic factors for PSCCE. In the validation step, OS was shown to be well-calibrated (C-index = 0.724), and a satisfactory clinical utility was proven by DCA. In conclusion, our findings revealed that CD155 and TIGIT are highly expressed in patients with PSCCE and are associated with shorter OS and PFS, supporting their role as prognostic biomarker.

Highlights

Primary small cell carcinoma of the esophagus (PSCCE) is a rare but aggressive disease that is associated with early metastasis and poor prognosis (Lv et al, 2008; Chen et al, 2016; Wong et al, 2017; Xu et al, 2017)
We found that high CD155 or TIGIT levels are associated with lower overall survival (OS) and progression-free survival (PFS)
CD155 is a member of the nectin-like family of adhesion molecules that has a wide variety of functions relevant to cancer, including tumor cell-intrinsic activities that regulate proliferation, adhesion, and migration as well as the ability to affect immune responses by binding to the immunomodulatory receptors DNAM-1, CD96, and TIGIT (Li et al, 2018)

Summary

Introduction

Primary small cell carcinoma of the esophagus (PSCCE) is a rare but aggressive disease that is associated with early metastasis and poor prognosis (Lv et al, 2008; Chen et al, 2016; Wong et al, 2017; Xu et al, 2017). Patients with PSCCE are usually treated by surgical resection, chemotherapy (CT), and radiotherapy (RT) either alone or in combination (Meng et al, 2013; Wang et al, 2015; Zou et al, 2016; Xu et al, 2017). The human CD155 molecule was first discovered by Mendelsohn et al (1989) and it has since been found to be broadly upregulated in malignant cells in solid tumors (Takai et al, 2008; Chandramohan et al, 2017). Li et al found that CD155-depleted tumor cells displayed slower tumor growth and reduced metastases, demonstrating the importance of the tumor-intrinsic role of CD155 (Li et al, 2018). The role of CD155 in tumor proliferation and invasion in PSCCE is of considerable interest

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