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Abstract
The poor prognosis of esophageal squamous cell carcinoma (ESCC) is mainly attributed to higher lymphatic-related metastatic ability. Whether the loss of expression of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is associated with lymphatic-related metastasis needs elucidation. In the present study, we assessed the mRNA and protein level of PTEN in ESCC by qRT-PCR and immunohistochemistry. The results showed PTEN mRNA level in tumors was significantly lower than that in corresponding non-tumor esophageal epitheliums (p<0.001), while 38 (51.4%) tumor samples were negative for expression of PTEN in ESCC tumors. Then the association between negative expression of PTEN and lymphatic-related metastasis (lymph node metastasis/3-year postoperative lymphatic metastatic recurrence) was evaluated. The proportion of PTEN-negative expression was significantly higher in positive lymph node metastasis (pN+) than that in negative lymph node metastasis (pN0) (p=0.021). The negative expression of PTEN was not an independent risk factor for the lymphatic recurrence rate in multivariate analysis (p=0.498), however, the lymphatic recurrence rate (60.5%) in PTEN-negative expression group was higher than that (36.1%) in PTEN-positive expression group (p=0.019). Furthermore, PTEN expression was stably silenced by lentiviral-vectored shRNA (Lenti-shRNA) in Eca109 (ESCC-derived cell line) to study functional effect of PTEN in vitro and in vivo. The laboratory study indicated increased cell proliferation, migration and invasion in vitro and more rapid growth rate of xenograft tumors in vivo after stable silencing of PTEN expression. Moreover, we proved that FAK/pFAK were not the main factors mediating the mechanism of metastasis in ESCC. In conclusion, negative expression of PTEN could be a useful biomarker to predict high risk for lymphatic-related metastasis in ESCC.
Highlights
Esophageal cancer is one of the most common cancers and the leading cause of cancer-related death worldwide
Lymphatic drainage of esophagus is fairly rich in mucoderm and muscularis mucosae, which lead to the higher incidence of lymphatic metastasis, comprising of lymph node metastasis and postoperative lymphatic metastatic recurrence
Loss of PTEN expression has been studied to correlate with lymph node metastasis in other tumors [11,12], the function of PTEN in esophageal squamous cell carcinoma (ESCC) is still debated [14,15,16]
Summary
Esophageal cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the predominant pathological type of esophageal cancer in China [1]. Surgical resection remains the best choice for treatment of ESCC [2]. The overall 5-year survival rate remains unsatisfactory with only 30-50% even after multimodal therapy [3]. Lymphatic drainage of esophagus is fairly rich in mucoderm and muscularis mucosae, which lead to the higher incidence of lymphatic metastasis, comprising of lymph node metastasis and postoperative lymphatic metastatic recurrence. It is reported to be the main factor resulting in the poorer prognosis [4].
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