Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3′UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.

BackgroundEsophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC.MethodsMultiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied.ResultsSLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro.ConclusionsCombined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0681-z) contains supplementary material, which is available to authorized users.

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Synovial sarcoma (SS) is an aggressive soft tissue tumor, with uncertain histological and cellular origin. SYT-SSX is considered to be responsible for sarcoma initiation and progression. The histogenesis and pathogenesis of this tumor are poorly understood, and prognosis of patients of SS is unsatisfactory. Recent studies have shown an association of cancer stem cells with the initiation and development of tumors. We explored immunohistochemical expression level of stem cell associated markers to determine the possible histogenesis and pathogenesis of SS. Fusion gene SYT-SSX was tested to assess diagnostic value and the molecular pathological features. We obtained the clinicopathological data of 20 SS patients, immunohistochemical staining were used to evaluate stem cell-associated markers included CD133, CD29, CD44, nestin, and ALDH1. Fusion gene SYT-SSX was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty SS cases were observed and the positive immuno-expression results showed CD133 (17/20), CD29 (11/20), CD44 (11/20), nestin (6/20), and ALDH1 (5/20). Fusion gene SYT-SSX was successfully detected by RT-PCR from 18 available samples. The expression of stem cell-associated markers (CD133, CD29, CD44, Nestin, and ALDH1) and clinical data (age, gender, sites, tumor size, histological type, tumor stage, and distant metastases) did not show statistically significant relationship (P>0.05), whereas, statistically significance between ALDH1 and metastases was observed (P<0.01). The ALDH1 positive synovial sarcoma (ALDH1+ SS) cases had significantly poor prognosis compared to ALDH1 negative synovial sarcoma (ALDH1- SS) cases (P<0.05). Immunohistochemical results indicated different expression levels of the five cancer stem cell markers in SS suggesting that SS may arise from cancer stem cells. Fusion gene SYT-SSX may play a critical role in the molecular pathological of SS.

The clinical value of synuclein-γ (SNCG) in oral squamous cell carcinoma (OSCC) was evaluated by detecting the expression of SNCG in saliva and tissues and its correlation with clinicopathological parameters (age, gender, ethnicity, degree of differentiation, clinical stage, and lymph node metastasis). Salivary samples were collected from 79 patients with OSCC, 31 patients with oral premalignant lesions (OPMLs), such as oral lichen planus, oral leukoplakia, and erythema, and 80 controls, and levels of SNCG in salivary samples were determined by enzyme-linked immunosorbent assay (ELISA). Tissue expression in formalin-fixed tissue biopsies of 94 cases of OSCC and 30 adjacent normal tissues was analyzed by immunohistochemistry (IHC) using an antibody against SNCG. The results showed that the salivary levels of SNCG in patients with OSCC and OPMLs were significantly higher than those detected in the control group (p<0.001). The immunohistochemical results showed that SNCG was highly expressed in tumor cells of OSCC patients, with low expression in the adjacent normal epithelium (p<0.001, OR=6.074). Salivary SNCG level correlated with differentiation (p=0.022). Besides, the expression of SNCG in OSCC tissues was also significantly associated with differentiation (p<0.001).

The purpose of this retrospective study was to evaluate the clinicopathological features of papillary thyroid microcarcinoma (PTMC) and the lymph node metastasis of PTMC. We retrospectively reviewed a total of 1433 patients with PTMC. The analysis data including demographics, tumor size, multifocality, bilateral, invasion capsule and Hashimoto's thyroiditis were collected from XinJiang, China. Univariate and multivariate analyses were performed to identify the clinicopathologic predictors of central lymph node metastasis: male gender [odds ratio (OR) = 2.358, p < 0.001], age ≤ 45 years (OR = 2.302, p < 0.001), sum of tumor size > 6.5 mm (OR = 2.388, p < 0.001), adjacent or invasion capsule (OR = 1.750, p = 0.002), Hashimoto's thyroiditis (OR = 0.501, p < 0.001). The optimal critical value of the number of dissected lymph nodes was found to be 8.5 using ROC analysis, with a sensitivity and specificity of 41.8% and 75.5%, respectively. This study suggests that evaluation of nodal metastasis is required to guide the surgical treatment of PTMC patients.