| Background:Colon Cancer(CC)is one of the most common causes of malignant tumor death.According to the latest relevant statistics,the proportion of colon cancer related deaths is in the front rank of cancer-related deaths in the world.At present,the treatment of CC is mainly based on radical resection combined with perioperative adjuvant chemoradiotherapy and molecular gene targeted therapy,and the choice of postoperative treatment and prognosis of CC mainly depends on surgical pathological staging.Therefore,it is of great significance to find potential high-sensitivity molecular targeted markers for the diagnosis and treatment of CC and the judgment of long-term outcomes after surgery.Tumor necrosis factor-alpha-induced protein 8 like 1(TNFAIP8L1),also known as TIPE1,is a newly discovered member of TIPE family.Relevant studies suggest that it plays an important role in the regulation of tumor occurrence and development.However,the expression and mechanism of TIPE1 in CC need to be further explored.This study aims to clarify the correlation between the expression of TIPE1 and prognosis of CC,provide theoretical basis for TIPE1 as a new targeted molecular marker for the diagnosis and prediction of patient survival,and clarify the important malignant biological effect mechanism of TIPE1 in the occurrence and development of CC cells.Materials and methods:In this study,public database data mining was conducted to clarify the expression of TIPE1 in CC.And the clinicopathological data of 181 CC patients in the Affiliated Hospital of Qingdao University were retrospectively collected.The expression of TIPE1 in CC and normal tissues was detected by immunohistochemistry.At the same time,the correlation between TIPE1 and clinical characteristics,tumor malignancy and postoperative clinical outcomes of CC patients was analyzed.In addition,two CC cell lines,SW480 and RKO,were selected for in vitro cell experiments in this study.In order to further explore the malignant biological mechanism of TIPE1 in CC,SW480 and RKO cell lines overexpressing TIPE1 were constructed and the effects of TIPE1 on the proliferation and motility of CC cells were studied by using a variety of cell-based experiments.Results:The expression level of TIPE1 was found to be lower in CC cells than in normal colon cells(P< 0.001).In addition,the expression level of TIPE1 was correlated with tumor TNM stage(P< 0.001),tumor lymph node metastasis(P< 0.001),tumor location(P< 0.001),and tumor malignancy(P= 0.016)in CC patients.K-M survival analysis showed that patients with high TIPE1 expression in CC tissues had a better prognosis than those with low TIPE1expression(P< 0.001).In addition,univariate and multivariate Cox regression model analysis of relevant patient survival outcomes showed that overall survival(OS)of CC patients was negatively correlated with TNM stage and tumor differentiation grade,but positively correlated with TIPE1 expression.On the other hand,in vitro cellular functional assays in the present study showed that when CC cell line TIPE1 was overexpressed,FBXW5 expression was increased and CC cell proliferation and motility were decreased,while when the increase of FBXW5 expression was inhibited,CC tumor cell proliferation and migration motility were restored.Conclusions:In conclusion,TIPE1 expression was significantly down-regulated in CC compared to normal colon tissues.In addition,the expression level of TIPE1 is correlated with tumor progression,and its low expression level predicts worse prognostic survival of CC patients.Overexpression of TIPE1 inhibits the proliferation and motility of CC cells,and FBXW5 is likely to be involved in the process of TIPE1 inhibiting the proliferation and motility of CC cells. |
