SIRT1 expression is associated with lymphangiogenesis, lymphovascular invasion and prognosis in pN0 esophageal squamous cell carcinoma.
BACKGROUND
Sirtuin1 (SIRT1) is an NAD(+)-dependent type III histone deacetylase (HDAC). This research investigated the prevalence of SIRT1 protein expression and its prognostic influence with the aim of validating its potential role in lymphangiogenesis and lymphovascular invasion (LVI) in pN0 esophageal squamous cell carcinoma (ESCC).


METHODS
A total of 206 patients were enrolled in this retrospective study. SIRT1 and VEGF-C protein expression was detected by immunohistochemical staining. Peritumoral lymphatic microvessel density (LVD) and LVI were evaluated by immunostaining for D2-40. Statistical analysis was then preformed to investigate the relevance of SIRT1 expression and various clinicopathologic features and to examine the effect of SIRT1 on tumor-induced lymphangiogenesis, LVI and prognosis.


RESULTS
SIRT1 positive expression was identified in 95 cases in the nucleus and was significantly correlated with T status (P < 0.001), disease stage (P = 0.001), VEGF-C positive expression (P = 0.015), high LVD (P = 0.013) and positive LVI (P = 0.015). Patients with SIRT1 positive expression, high LVD and positive LVI had a significantly unfavorable 5-year disease free survival (P < 0.001, P = 0.030, and P < 0.001, respectively) and overall survival (P < 0.001, P = 0.017, and P < 0.001, respectively). However, based on multivariate Cox regression analysis, only SIRT1 positive expression and positive LVI were significant independent prognosticators of poor disease-free survival (P = 0.029 and 0.018, respectively) and overall survival (P = 0.045 and 0.031, respectively).


CONCLUSIONS
SIRT1 positive expression was significantly associated with tumor progression, lymphangiogenesis, LVI and poor survival in pN0 ESCC patients. Our research shows a utilization of SIRT1 in prognosing poor survival and providing possible target for ESCC patients through inhibiting its lymphangiogenesis activity.
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Guan-Qing
GQ
Chen
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Hui
H
Tian
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Wei-Ming
WM
Yue
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Lin
L
Li
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Shu-Hai
SH
Li
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Lei
L
Qi
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Cun
C
Gao
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Li-Bo
LB
Si
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Ming
M
Lu
Department of Thoracic Surgery, Qi Lu Hospital, Shandong University, Wen hua xi lu 107#, Jinan, 250012 Shandong Province China.
Fei
F
Feng
Esophageal squamous cell carcinoma; Lymphangiogenesis; Lymphatic metastasis; Prognosis; SIRT1