HCC is a prevalent malignancy with insidious onset. Tumor stage at diagnosis and appropriate therapy are key for outcomes of HCC patients . To data, there is no available tool for early detection of the disease, due to the unclear etiology and pathogenesis . Consequently, most of the patients are diagnosed at an advanced stage, resulting in low survival rate. The detection of biomarkers in body tissues or fluids are considered as a promising way to improve the diagnostic accuracy of HCC . Serum AFP (alpha fetoprotein) is one of the major biomarkers for HCC diagnosis currently. Despite of high specificity, the low sensitivity of AFP may lead to missed diagnosis . Hence, more specific and sensitivity tumor markers are urgently needed for HCC research.
HTATIP2 is a tumor metastasis-related gene which is primitively discovery by Shtivelman et al. . HTATIP2 plays inhibitory roles in tumorigenesis via regulating various processes, such as inhibiting tumor growth, inducting cancer cell apoptosis, weakening athletic ability, and so on [14-16]. As a tumor suppressor gene, HTATIP2 has been reported to be involved in the development and progression of various caners. Chen et al. reported that promoter methylation caused down-regulation of HTATIP2 that contributed to tumor progression of colorectal cancer . Tong et al. suggested that HTATIP2 was down-regulated in lung cancer and its decreased expression showed significant association with metastatic potential of the disease . In this study, we determined the expression pattern of HTATIP2 in HCC, as well as its functional roles in tumor progression.
In the current study, we found that HTATIP2 mRNA level was down-regulated in HCC patients compared with the healthy controls. Besides, chi-square test demonstrated that the reduced expression of HTATIP2 might contribute to positive venous invasion, lymph node metastasis and advanced TNM stage. The above findings hinted that HTATIP2, as a tumor suppressor, was involved in the development and progression of HCC. The conclusion was consistent with the previous studies. A related study carried out by Zhu et al. demonstrated that HTATIP2 was decreased in HCC patients and its expression level showed close association with E-cadherin expression. Cell experiments proved that down-regulated HTATIP2 expression contributed to activated EMT, as well as enhanced invasion and motility of HCC cells, suggesting the inhibitory function of the gene in malignant development and progression of HCC .
As an important tumor suppressor, HTATIP2 was proved to play a predictive role in tumor initiation and progression. In pancreatic ductal adenocarcinoma, decreased expression of HTATIP2 predicted poor prognosis for the patients . Among gastric cancer patients, reduced expression of HTATIP2 represented dismal overall survival. In the present study, we evaluated the diagnostic value of HTATIP2 in HCC. ROC curve demonstrated that HTATIP2 could discriminate between HCC patients and healthy controls with satisfactory sensitivity and specificity. Though we had confirmed the low expression of HTATIP2 in HCC patients and identified its diagnostic role in this malignancy, its precise mechanism on this disease was still not well understood. Accumulating evidences proved that HTATIP2 might be linked with the development and progression of angiogenesis in HCC, which was realized through modulating the transcription of angiogenesis regulator . Besides, it was also proposed that HTATIP2 served as a tumor suppressor via inducing cell apoptosis in HCC . All the related researches could provide theoretical foundations for our further studies.