Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a highly invasive lesion that frequently metastasizes to the cervical lymph nodes and is associated with a poor prognosis. Several adhesion factors, including cadherin 6 (CDH6), cadherin 11 (CDH11) and cluster of differentiation 44 (CD44), have been reported to be involved in the invasion and metastasis of multiple types of cancer. Therefore, the aim of the present study was to determine the expression of CDH6, CDH11 and CD44 in tumor tissues from patients with OSCC, and whether this was associated with the metastasis and survival of OSCC. The mRNA expression of the human tumor metastasis-related cytokines was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OSCC tumors with or without lymph node metastasis (n=10/group). The expression of CDH6, CDH11 and CD44 in 101 OSCC and 10 normal oral mucosa samples was examined by immunohistochemical staining. The association between overall and disease-specific survival times of patients with OSCC and the expression of these three proteins was evaluated using Kaplan-Meier curves and the log-rank test. RT-qPCR results indicated that the mRNA expression of CDH6, CDH11 and CD44 was increased in OSCC patients with lymph node metastasis (2.93- 2.01-and 1.92-fold; P<0.05). Overexpression of CDH6, CDH11 and CD44 was observed in 31/35 (89%), 25/35 (71%) and 31/35 (89%) patients, respectively. The number of OSCC patients with lymph node metastasis exhibiting CDH6, CDH11 and CD44 overexpression was significantly higher than the number of patients without lymph node metastasis exhibiting overex;pression of these proteins (P=0.017, P=0.038 and P=0.007, respectively). OSCC patients with high co-;expression of CDH6, CDH11 and CD44 exhibited lower disease-specific survival times (P=0.047; χ2=3.933) when compared with OSCC patients with low co-;expression of these adhesion factors. CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use of these factors as biomarkers may improve the accuracy of the prediction of cancer metastases and prognosis.