The Study On The Effects Of STC2 And Its Related Protein HMGA2 In Colorectal Cancer

Colorectal cancer(CRC)is one of the main causes of cancer-related death worldwide.In recent years,although great advances have been made in investigating the molecular basis of CRC,the exact mechanism underlying the carcinogenesis of CRC.remains unclear.Detection of circulating cell-free mRNA serves as a noninvasive and effective tool for cancer diagnosis.Stanniocalcin 2(STC2),a secreted glycoprotein,has been suggested to exert various functions in progression of many cancers.However,its biological role in CRC is not fully understood.Our previous data showed that STC2 was highly correlated with HMGA2 expression.STC2 was found to be directly regulated by HMGA2 at the transcriptional level in high-grade serous ovarian cancers.As an oncofetal protein,HMGA2 is highly expressed in CRC tissues.However,it is not clear whether the level of circulating cell-free HMGA2 mRNA functions as a potential biomarker in diagnosis and prognosis for CRC patients.In the present study,the levels of STC2 expression were found to be statistically higher in CRC than that in adjacent control tissues from TCGA and GEO database.Increasing mRNA levels of STC2 were significantly correlated with left-sided CRC,rectal cancer,positive lymph node involvement,advanced T-stage and AJCC-stage in TCGA database.In addition,the mRNA levels of STC2 was found to be negatively associated with the expressions of epithelial cell markers,whereas it was positively associated with the mRNA levels of MMPs,the EMT-related transcriptional factors and mesenchymal cell markers.Furthermore,our data showed that STC2 promoted cell migration and invasion in CRC cells in vitro.And a group of differentially expressed genes regulated by STC2 were screened by RNAseq.To evaluate the clinical importance in the diagnosis and prognosis of CRC,we assessed serum levels of circulating HMGA2 mRNA in 83 CRC patients and 11 healthy volunteers.The mRNA levels of plasma HMGA2 were evaluated by real-time quantitative RT-PCR.Then the relationship between its expression and clinicopathologic characteristics were analyzed.When it was compared with the healthy volunteers,the circulating cell-free HMGA2 mRNA were significantly higher in CRC patients.Our results also showed that the patients with right-sided CRC,microsatellite stable(MSS)status,vascular invasion,nerve infiltration,and higher serum CA199 had higher expressions of circulating cell-free HMGA2 mRNA.Furthermore,HMGA2 mRNA levels were significantly correlated in both plasma and CRC tissues.