Suppressor PAQR3 associated with the clinical significance and prognosis in esophageal squamous cell carcinoma

Abstract

Progestin and adipoQ receptor family member 3 (PAQR3) is a novel tumor suppressor; however, its function in esophageal cancer is not well understood. The present study explored the association between PAQR3, and the survival and clinical phenotype in patients with esophageal squamous cell carcinoma (ESCC). The expression of PAQR3 in 80 cases of ESCC and its corresponding adjacent tissues was detected by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that PAQR3 expression in cancer tissues was significantly lower compared with that in adjacent tissues. Clinicopathological analysis indicated that PAQR3 expression was significantly correlated with ethnicity (P=0.032), tumor length (P=0.019), lymph node metastasis (P=0.011) and local recurrence (P=0.009). Notably, the Kaplan-Meier survival curve demonstrated that a decrease in PAQR3 expression was associated with poor prognosis in patients with ESCC. Multivariate analysis indicated that PAQR3 expression was an independent prognostic indicator for patients with ESCC. PAQR3 may serve an important role in the progress of ESCC and become a potential candidate for ESCC targeted therapy.

Keywords: esophageal squamous cell carcinoma; extracellular signal-regulated kinase; progestin and adipoQ receptor family member 3; prognosis; suppressor.

Figure 1.

Expression of PAQR3 is reduced in ESCC samples. (A) The relative level of PAQR3 mRNA in human ESCC tissues in comparison with PCHNT specimen from 80 patients with esophageal cancer. PAQR3 mRNA level was determined by quantitative reverse transcription-quantitative polymerase chain reaction and adjusted for GAPDH. (B) The relative ratio of PAQR3 mRNA in the cancer samples vs. PCHNT samples. PCHNT, paracancerous histological normal tissue; PAQR3, progestin and adipoQ receptor family member 3; ESCC, esophageal squamous cell carcinoma.

Figure 2.

Expression of PAQR3 protein is reduced in ESCC samples. (A) Representative IHC images of PAQR3 expression are shown for normal esophageal tissue, PCHNT and cancer tissues, magnification, ×200. (B) The relative ratio of PAQR3 protein in the cancer samples vs. PCHNT samples. (C) The correlation between PAQR3 mRNA level (tumor/PCHNT) as determined by reverse transcriptase-quantitative polymerase chain reaction and PAQR3 protein level as determined by IHC in 80 esophageal cancer tissues. *P<0.001. IHC, immunohistochemistry; PCHNT, paracancerous histological normal tissue; PAQR3, progestin and adipoQ receptor family member 3.

Figure 3.

Correlation of PAQR3 expression level with survival of patients with ESCC. Kaplan-Meier curves of (A) OS and (B) DFS in post-surgery patients with ESCC according to the expression level of PAQR3. OS, overall survival; DFS, disease-free survival; PAQR3, progestin and adipoQ receptor family member 3; ESCC, esophageal squamous cell carcinoma.

Figure 4.

PAQR3 suppresses epithelial-mesenchymal transition features in human esophageal squamous cancer cells. Western blot analysis of indicated proteins in ECA-109 and TE-1 cells transfected with the PAQR3-expressing plasmid or vector (n=3). (A) The phosphorylation of Akt was not altered by PAQR3 overexpression. (B) ECA-109 and TE-1 cells with overexpression PAQR3 were used to analyze the expression of epithelial markers E-cadherin. E-cadherin, epithelial-cadherin; PAQR3, progestin and adipoQ receptor family member 3; p, phosphorylated; Akt, AKT serine/threonine kinase 1.