Co-expression of VEGF-C and survivin predicts poor prognosis in esophageal squamous cell carcinoma

Yun-Zhu Zeng; Yong-Qu Zhang; Xue-Qiong Lin; Jiong-Yu Chen; Fan Zhang; Jian-Ling Zhu; Xiao-Long Wei

doi:10.21037/tcr-20-2498

Co-expression of VEGF-C and survivin predicts poor prognosis in esophageal squamous cell carcinoma

Transl Cancer Res. 2021 Jan;10(1):210-222. doi: 10.21037/tcr-20-2498.

Authors

Yun-Zhu Zeng^#¹, Yong-Qu Zhang^#², Xue-Qiong Lin³, Jiong-Yu Chen⁴, Fan Zhang⁵, Jian-Ling Zhu¹, Xiao-Long Wei¹

Affiliations

¹ Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, China.
² Department of Breast-Thyroid-Surgery, Xiang'an Hospital of Xiamen University, Xiamen, China.
³ Clinical Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, China.
⁴ Oncological Research Lab, Cancer Hospital of Shantou University Medical College, Shantou, China.
⁵ Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, China.

^# Contributed equally.

Abstract

Background: Lymphatic metastasis is one of the main factors affecting prognosis in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor-C (VEGF-C) is an important factor that promotes lymphangiogenesis. Survivin also plays a significant role in lymphatic invasion. However, the role and mechanism of their co-expression are still unclear in ESCC. The purpose of this study was to investigate whether the co-expression of VEGF-C and survivin could be a potential marker to predict patient prognosis and survival in ESCC.

Methods: The levels of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR-3), survivin, and Ki-67 were determined by immunohistochemistry (IHC) in 97 ESCC patient tumors. The correlations of co-expression of VEGF-C and survivin with pathological features and survival results were also assessed.

Results: High VEGF-C expression was observed in 64.9% of the patients and significantly correlated with T stage (P=0.024), node status (P=0.038), and lymph node metastasis (P=0.015). High survivin expression was significantly associated with T stage (P=0.013), N stage (P=0.016), lymph node metastasis (P=0.005), and differentiation (P=0.044) in 67.0% of the patients. Co-expression of VEGF-C and survivin (V+S+) was significantly associated with T stage (P<0.001), N stage (P=0.015), lymph node metastasis (P=0.003), differentiation (P=0.0045), and Ki-67 levels (P=0.024). High expression of VEGF-C or survivin was associated significantly with worse disease-free survival (DFS) and overall survival (OS) (P<0.05). Moreover, the V+S+ group had a worse DFS (P<0.001) and OS (P=0.001) than any other group (i.e., V-S-, V+S-, V-S+). Furthermore, multivariate DFS analyses (95% CI: 1.147-2.220, P=0.006) and multivariate OS analyses (95% CI: 1.080-2.193, P=0.017) revealed that co-expression of VEGF-C and survivin was an independent prognostic factor in ESCC patients.

Conclusions: Co-expression of VEGF-C and survivin was predictive of poor prognosis in ESCC. Combined detection of VEGF-C and survivin could represent a feasible and effective marker to predict the prognosis and survival of ESCC patients.

Keywords: Vascular endothelial growth factor-C (VEGF-C); esophageal squamous cell carcinoma (ESCC); lymph node metastasis; prognosis; survivin.