The Correlation Analysis Between The Expression Of MiR-195 And Cdc42 And The Prognosis In Esophageal Squamous Cell Carcinoma

BackgroundEsophageal cancer is a common digestive system malignant tumor with a high incidence rate and low 5-year survival rate, where the highest incidence rate is in Lin County, Anyang city of Henan Province. In clinical work, the determination of clinical outcome is mainly referenced by clinical pathology features, such as TNM classification. However, it had been found that the TNM classification is not very accurate to predict the prognosis of the patients in a large-scale epidemiological survey. It is extremely important to identify accurate biomarkers. Previous study has found that miR-195 and Cdc42 may be involved in the process of esophageal squamous cell carcinoma, but their expression in human esophageal squamous cell carcinoma and the clinical significance are not immediately clear. Therefore, it will be of great significance to carry out the study to find biomarkers of esophageal carcinoma for prognosis assessment.ObjectiveTo investigate the expression and clinical pathological features of miR-195 and Cdc42 in Esophageal Squamous Cell Carcinoma (ESCC), and the relationship betweenthemiR-195 combined Cdc42 and the prognosis of patients with esophageal cancer, aiming to provide clinical guidance for the treatment and survival prognosis of the patients.MethodsCollected intraoperative pathological specimens and clinical data of 98 cases of esophageal squamous cell carcinoma and followed up until December 2013 to record the survival time of patients. respectively. The follow-up examination intervals was carried out every 3 months in the first year 1, and every six months in the second year. Diagnostic tests included esophageal imagingCT scans, chest X-ray, abdominal ultrasound and bone scan to find the recurrence or metastasis in all the cases. Using the procedure of qRT-PCR to detect the expression of miR-195 and Cdc42 in 98 pairs of esophageal squamous cell carcinoma, adjacent tissues and 10 cases of normal esophageal tissues, respectively. We retrieved the 571 patients in a cancer hospital of high incidence area,organized their clinical pathologica 1 information and pathological specimens.98 cases were randomly selected for the study. There were 98 pathological specimens and 10 normal esophageal tissues. All fresh pathological specimens were frozen in liquid nitrogen or stored at-80 ℃ refrigerator until RNA was extracted to avoided freezing and thawing repeatedly and leading to protein denaturation during this period. Esophageal squamous cell carcinoma, adjacent tissues and normal esophageal tissues were stained by HE, and Nikon-E200 ordinary optical microscope was applied to determine the pathological type. Statistical methods were utilized to analyze the relationship between expression of miR-195 and Cdc42 and clinical pathology, and prognostic models were analyzed by Kaplan-Meier survival analysis, log-rank test and Cox proportional hazard.Results1. The result of HE stain showed that:in all experimental esophageal tissue specimens, 98 cases were squamous cell carcinoma; 98 cases of adjacent tissues were normal esophageal tissues determined by the morphology; 10 cases were normal esophageal tissue.2. The expression of miR-195 was generally down-regulated in esophageal squamous cell carcinoma. The real-time PCR results showed that:compared with the adjacent tissues and normal esophageal tissues, the miR-195 in esophageal squamous cell carcinoma was down-regulated, which had a significant difference (P<0.001); Compared with the adjacent tissues and normal esophageal tissues,the expression of Cdc42 in esophageal squamous cell carcinoma was generally up-regulated (P<0.001) and the difference was significant. The miR-195 and Cdc42 mRNA expression levels in esophageal squamous cell carcinoma was negatively related to each other. (Spearman correlation P<0.001).3.The relationship among the expression of miR-195、Cdc42 and clinical pathological features showed that:the lower expression of miR-195 was significantly associated with TNM stages and lymph node metastasis (P<0.05);There is a significantly correlation between the high expression of Cdc42 and TNM stage and tumor differentiation (P<0.05).4.Kaplan-Meier survival analysis showed that. The overall survival (OS) and progres-sion-free survival (PFS) of patients with esophageal squamous cell carcinoma in Low-miR-195 group or High-Cdc42 group were much worse than the High-miR-195 group or Low-Cdc42 group (P<0.001).In addition, the OS and PFS were worst in miR-195-low/ Cdc42-high, whereas the OS and PFS of miR-195-high/Cdc42-low were best.5.Cox rate model showed that:TNM, tumor differentiate, lymph nodes metastasis, low expression of miR-195, high expression ofCdc42, co-expression of Low-miR-195/ High-Cdc42were independent risk factors for the prognosis of esophageal squamous cell carcinoma.ConclusionThe decrease of miR-195 expression, up-regulation of Cdc42 expression, and the co-expression of miR-195/Cdc42 may be associated with the development and progress-ion of esophageal squamous cell carcinoma, which could be a marker of poor prognosis in esophageal squamous carcinoma.