ABSTRACT
OBJECTIVE: We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear. METHODS: We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells. RESULTS: DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T-stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease-free survival (DFS), respectively. Survival analyses revealed that DKK3-positive cases and CKAP4-positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double-negative cases showed significantly favorable prognosis. Both anti-DKK3Ab and anti-CKAP4Ab could suppress cancer cell proliferation, migration, and invasion. CONCLUSION: DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Proto-Oncogene Proteins c-akt/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Squamous Cell Carcinoma of Head and Neck , Prognosis , Cell Proliferation , Cell Line, Tumor , Membrane Proteins/metabolism , Adaptor Proteins, Signal TransducingABSTRACT
BACKGROUND: End-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PURPOSE: To clarify the clinical implications of ADPAF in adults. METHODS AND RESULTS: The study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSEâ <17 mm) and preserved RV function (P-RVF) group (5 patients with TAPSEâ ≥17 mm). In the R-RVF group, four patients died, one patient underwent left ventricular assist device implantation, and two patients underwent unplanned hospitalization for heart failure during follow-up. The R-RVF group had poorer prognosis and higher mortality rate compared with the P-RVF group. CONCLUSIONS: ADPAF reflects RV restriction in adults. ADPAF suggests a less favorable prognosis in patients with R-RVF.
