Study On The Expression Of TUFT1 And Rab5-GTP In Triple Negative Breast Cancer

Background Breast cancer has become the most universal type of cancers among women all around the world with the second mortality rate.No matter in developing countries or in developed countries,the prevalence rate of breast cancer is progressively increasing.Although the survival rate of breast cancer has augmented,there is still disparate in different countries due to the lack of early screening,detection and cost-effective treatments.The specific pathogenesis of breast cancer is unknown,but it is currently believed that drinking,high body mass index,high blood sugar,and low physical activity are all risks for its onset,and the risk factors of different subtypes are not the same^[1].As one of the subtypes of breast cancer,TNBC（Triple-negative Breast Cancer）is more common in young women,African and Hispanic women,especially in women with BRCA1 gene mutations^[2].Compared to other subtypes,Patients with TNBC are with higher risk of local and distant recurrence or metastasis.At present,cytotoxic chemotherapy is still a standard treatment for TNBC.Exploring biomarkers and their targeted drugs is one of the research prospects to achieve precise treatment of TNBC.TUFT1（Tuftelin1）was originally thought to play a role in the mineralization of enamel covering vertebrate teeth.It was later discovered that TUFT1 was also expressed in non-mineralized tissues and various tumor tissues,in which related to the biological behavior of tumor cells.The expression of TUFT1 was significantly obvious and positively related to the multiplication and metastasis of tumor cells of pancreatic cancer,hepatoma,lung cancer,carcinoma of thyroid and mammary cancer,etc.Rab is an important branch of the Ras superfamily.Almost all eukaryotic organisms are of Rab expression.So far,nearly70 kinds of Rab proteins have been found in human cells^[3].Rab5 is a member of the Rab family.It is located in vesicles,plasma membranes and early endosomes,activated as the form of Rab5-GTP,and participates in multiple steps of vesicle transport.Abnormal expression of Rab5 will affect cell proliferation,differentiation and apoptosis.Rab5 was found highly expressed in variety kinds of malignant tumors affiliated to reproductive system,respiratory system and digestive system,as well as thyroid cancer and breast cancer,and the positive rate was remarkably higher than that in normal tissues.Up to now,there are few reports related to the expression of TUFT1 and Rab5 in TNBC,as well as their correlation to prognosis.Objective To observe the expression of TUFT1 and Rab5-GTP in TNBC,to analyze the interrelationship between them and then explore the impact of their expression to clinicopathological features of carcinoma and to the clinical prognosis.Methods A total of 57 TNBC patients admitted to Dalian Central Hospital Affiliated to Dalian Medical University from January 2014 to June 2015 met the inclusion and exclusion criteria,and their paraffin sections after surgical,complete clinical pathological data and 5-year follow-up data were collected.Immunohistochemical analysis was used to evaluate the expression level of TUFT1 and Rab5-GTP in TNBC cancer tissues and adjacent tissues.Then we used SPSS25.0 to performχ² test to analyze whether there was a difference in expression of these two proteins in carcinoma tissues and para-carcinoma tissues and the connection with clinicopathological factors;We used Spearman rank correlation test to check the correlation between the two proteins;According to the expression of TUFT1 and Rab5-GTP,patients were divided into four groups,TUFT1+/Rab5-GTP+,TUFT1+/Rab5-GTP–,TUFT1–/Rab5-GTP+and TUFT1–/Rab5-GTP–.Kaplan-Meier was used for survival analysis to explore the influence of their expression on the prognosis.Results（1）TUFT1 expressed remarkably more in cancerous tissues than in para-cancerous tissues in TNBC（59.6%vs 17.5%,χ²=21.3,P<0.01）,and Rab5-GTP expressed remarkably more in cancerous tissues than in para-cancerous tissues in TNBC（57.9%vs24.6%,χ²=13.1,P<0.01）.（2）In the carcinoma tissues of TNBC,the expression degree of TUFT1 was positively correlated with lump size,histopathological grade and lymphatic gland metastasis（χ²=7.0,P=0.008;χ²=4.4,P=0.035;χ²=6.9,P=0.009）,while had nothing to do with the patients’years and position of carcinomas（P>0.05）.The expression of Rab5-GTP was positively correlated with lump size and lymphatic gland metastasis（χ²=5.5,P=0.019;χ²=4.1,P=0.044）,but had nothing to do with patient’s age,tumor location,and histopathological grade（P>0.05）.（3）In TNBC,TUFT1 positively weak correlated to Rab5-GTP（P=0.018<0.05,r_s=0.313）.（4）Among 57 TNBC patients,the 5-year OS and PFS of group TUFT1+/Rab5-GTP+was the best one（65.2%,15/23;87.0%,20/23）,and then were group TUFT1+/Rab5-GTP-（50.0%,5/10;70%,7/10）and group TUFT1-/Rab5-GTP+（33.3%,3/9;66.7%,6/9）,and the worst 5-year OS and PFS were of group TUFT1+/Rab5-GTP+（6.7%,1/15;46.7%,7/15）.The differences were statistically significant（P<0.01）.Conclusion The positive rate of TUFT1 and Rab5-GTP in TNBC carcinoma tissues was remarkably higher than that in para-carcinoma tissues,and were associated with worse clinicopathological features of tumors.The expression of the two protein had a positive correlation.High expression of them at the same time indicated a worse prognosis of patients.The research on TUFT1 and Rab5-GTP is expected to provide new targets for the prognosis and treatment of patients with TNBC.