Expression Of Long Non-coding RNA TINCR In Esophageal Squamous Carcinoma And Its Relationship With Radiosensitivity

Objective: To clarify the relationship between the expression of TINCR（Terminal differentiation-induced lnc RNA,TINCR）in esophageal squamous carcinoma tissues and adjacent tissues with clinicopathological characteristics and prognosis.The correlation between the expression of TINCR in peripheral blood and the radiosensitivity in esophageal cancer patients was examined.Explore the potential biological role of TINCR in the progression of esophageal cancer through cell function test.Materials and Methods: Collect primary cancer tissues and adjacent tissues with a distance of more than 3 cm from patients undergoing esophageal squamous cell carcinoma surgery in the Hospital from March 2017 to December 2018.Patients with missed information and whose inconsistent with this study were excluded,and 65 cases of esophageal squamous cell carcinoma were selected to study the clinicopathological characteristics and prognosis of those survived.In order to further study whether the expression of TINCR in peripheral blood is related to radiotherapy,the peripheral blood of 53 newly diagnosed patients with radiotherapy before and after radiotherapy was selected,and the peripheral blood of 40 healthy patients was randomly selected to analyze the difference of expression in peripheral blood.By comparing the results of esophageal barium meal and CT examination before and after radiotherapy,patients were divided into radiotherapy sensitive group and radiotherapy resistant group according to the evaluation standard of solid tumor.The correlation between the expression of TINCR and the curative effect of radiotherapy was analyzed.CCK-8,wound healing assay,transwell migration assay,clone formation test and flow cytometry were used to study the biological role of TINCR in esophageal cancer cell line.Results: 1.The expression level of TINCR in TE-1,TE-13,ECA109 and KYSE150 is higher than human normal esophageal epithelial cells（HEEC）.Compared with adjacent normal tissues,the expression level of TINCR in esophageal squamous cell carcinoma was also significantly higher.Based on the median expression of TINCR,samples were divided into two groups: low TINCR expression group（n=33）and high TINCR expression group（n=32）.The analysis of clinical pathological features showed that the expression level of TINCR was related to the depth of tumor invasion,the size of tumor and lymph node metastasis,but not to gender,age,tobacco and alcohol.2.Patients with low TINCR expression group have better overall survival rate than patients with high TINCR expression group.Univariate cox regression analyses showed that depth of tumor invasion,the size of tumor,lymph node metastasis and TINCR expression level were related to the prognosis of patients.Multivariate cox regression analysis showed that compared with the prognostic factors such as tumor invasion depth,tumor size and lymph node metastasis,TINCR could be used as an independent prognostic factor.3.The expression level of TINCR in peripheral blood of patients with radiotherapy alone was detected,and the expression level of TINCR in patients with esophageal squamous cell carcinoma decreased after radiotherapy（P=0.028）.The expression level of TINCR in the radiotherapy sensitive group decreased after radiotherapy（P=0.020）,but there was no significant difference in TINCR in radiotherapy resistant group before and after radiotherapy（P=0.240）.4.CCK-8 proves that down-regulated TINCR can significantly inhibit the proliferation of cells.wound healing assay showed that down-regulated TINCR could inhibit the migration and repair ability of esophageal cancer cells,and transwell migration assay showed that the migration ability of esophageal cancer cells decreased after downregulated TINCR.Cell apoptosis and cycle experiments confirmed that down-regulated TINCR induced cell apoptosis,which made the cell cycle arrest in S phase.In the esophageal cancer cell line with down-regulated TINCR,the clone formation rate after radiotherapy is lower.Conclusion: 1.TINCR is highly expressed in esophageal squamous cell carcinoma.2.TINCR can be used as an independent prognostic factor,and its high expression may predict the poor prognosis of patients with esophageal squamous cell carcinoma,and may also be related to the radiotherapy sensitivity of patients with esophageal squamous cell carcinoma.After radiotherapy,the obvious decrease of TINCR in peripheral blood can predict the sensitivity of radiotherapy.3.In vitro experiments,down-regulation of TINCR can inhibit the proliferation and migration of esophageal cancer cells,promote apoptosis and block cell cycle,and can enhance the sensitivity of radiotherapy.