Histone deacetylase 6 expression in metastatic lymph nodes is a valuable prognostic marker for resected node-positive esophageal squamous cell cancer

Abstract

Xuan Xie,1,2,* Kongjia Luo,3–5,* Yi Li,3,4,6 Yihong Ling,3,4,7 Shuishen Zhang,8 Xiuying Xie,3,4 Jing Wen3,4 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 4Guangdong Esophageal Cancer Research Institute, Guangzhou, People’s Republic of China; 5Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 6Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 7Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 8Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Histone deacetylase 6 (HDAC6) exerts enzymatic deacetylation activity on histones and on non-histone substrates and plays a key role in microtubule dynamics and chaperone activities. In addition, previous studies have demonstrated its role in cancer progression. However, its clinical significance in esophageal squamous cell cancer (ESCC) has not been elucidated. We investigated the correlation of HDAC6 expression and clinical outcome in a group of T3N1–3M0 surgically resected ESCCs.Methods: Tissue microarrays were conducted on 209 surgically resected T3N1–3M0 ESCC tumors, including 163 pairs of primary tumors (PTs) and their corresponding metastatic lymph nodes (MLNs). Immunohistochemistry was utilized to evaluate HDAC6 protein levels. The relationship between patient outcomes and HDAC6 expression was analyzed statistically.Results: The level of HDAC6 expression in ESCC MLNs was found to be significantly lower than that in PTs (P<0.001). Patients with lower MLN HDAC6 expression demonstrated improved overall survival (P=0.011) and disease-free survival (P=0.012) than those with higher HDAC6 expression. HDAC6 expression levels in PTs revealed no prognostic significance. Multivariate analysis showed that the MLN HDAC6 expression level was an independent prognostic factor for both overall survival (HR 1.456, P=0.029) and disease-free survival (HR 1.432, P=0.033).Conclusion: High expression of HDAC6 in MLNs but not in PTs suggests a poor prognosis for patients with resected T3N1–3M0 ESCC. We should take into account the protein expression of MLNs when assessing prognosis in patients with lymph-node involvement. Keywords: esophageal cancer, HDAC6, biomarker, protein expression, outcomes

Keywords

• Esophageal cancer
• HDAC6
• biomarker
• protein expression
• outcomes