Clinical significance and prognostic value of SOX7 expression in liver and pancreatic carcinoma

Abstract

Sex determining region Y-box 7 (SOX7) is known to function as a tumor suppressor in a number of types of cancer; however, its role in liver and pancreatic carcinoma remains unclear. The present study investigated the association between SOX7 expression and the clinical pathology of these carcinomas, in particular if SOX7 expression may be used to predict recurrence and patient prognosis following radical resection of liver and pancreatic carcinoma. SOX7 expression in human liver and pancreatic carcinoma was detected by immunohistochemical analyses and validated using mRNA data from a high-throughput sequencing dataset from The Cancer Genome Atlas (TCGA). SOX7 expression was significantly downregulated in liver and pancreatic carcinoma relative to the adjacent benign tissues [immunoreactivity scores: Liver carcinoma (3.53±1.57) vs. benign (7.00±0.00), P<0.001; and pancreatic carcinoma (2.39±1.88) vs. benign (4.80±0.45), P=0.005]. In addition, downregulation of SOX7 was significantly associated with advanced stage liver carcinoma, and the primary pathological tumor stage and regional lymph node stages. These findings were further validated in the TCGA dataset. However, SOX7 down regulation was closely associated with the only pathological grade in pancreatic patients. Kaplan-Meier analyses revealed significant differences in overall and disease-free survival between patients with high and low levels of SOX7 expression. In addition, a multivariate analysis with Cox regression indicated that SOX7 may be an independent predictor of disease-free survival. The results indicate that SOX7 may inhibit the progression of liver carcinoma and that SOX7 downregulation may accurately predict poor prognosis in liver carcinoma patients.

miR-146a Inhibited Pancreatic Cancer Cell Proliferation by Targeting SOX7

“…In a recent study, Guo et al demonstrated that the SOX7 gene was downregulated in 47% of the pancreatic adenocarcinomas, and tumor-specific inactivation of SOX7 by promoter hypermethylation was found in 48% of the primary pancreatic tumors tested [ 20 ]. These authors also suggested that SOX7 serves as an independent checkpoint for b-catenin function in pancreatic and colon epithelial cells [ 21 , 22 ]. Furthermore, many research studies indicated that SOX7 could be regulated to influence cancer progression or apoptosis by miRNAs [ 23 ].…”

Advance of SOX Transcription Factors in Hepatocellular Carcinoma: From Role, Tumor Immune Relevance to Targeted Therapy

“…Many SOX members show significant clinical implications in HCC. For instance, the overexpressed SOX4 or SOX12 is positively associated with the poor survival of HCC, while low SOX6 or SOX7 expression predicts shorter disease-free survival and overall survival, which provide potential diagnostic and prognostic markers for HCC [ 56 , 57 , 58 , 59 , 79 , 87 , 127 ]. In addition to serving as the predictors of diagnosis and prognosis, many SOX members are also potential therapeutic targets for HCC.…”

“…However, its expression level varies greatly among different tumor types, suggesting the existence of cancer cell-dependent mechanisms to regulate SOX7 expression [ 125 ]. In HCC, SOX7 is significantly down-regulated relative to adjacent non-tumor tissue and is associated with the advanced stage of HCC [ 126 , 127 ]. The low SOX7 expression predicts the poor prognosis of patients with HCC, which serves as an independent prognostic factor for HCC [ 127 ].…”

“…In HCC, SOX7 is significantly down-regulated relative to adjacent non-tumor tissue and is associated with the advanced stage of HCC [ 126 , 127 ]. The low SOX7 expression predicts the poor prognosis of patients with HCC, which serves as an independent prognostic factor for HCC [ 127 ]. As a tumor-suppressor factor, SOX7 inhibits HCC cell proliferation and induces cell cycle arrest by decreasing the expression of cyclin D1 and c-myc [ 126 ].…”

SOX7 is involved in polyphyllin D-induced G0/G1 cell cycle arrest through down-regulation of cyclin D1

“…SOX7, together with SOX17 and SOX18, comprises the SOXF subfamily, which participates in various biological processes, including the regulation of vasculogenesis (8), hematopoiesis (9), cardiogenesis (10), and myogenesis (11). Studies have reported that SOX7 acts as a tumor suppressor in the breast (12), lung (13), colorectal (14), liver (15), and gastric cancers (16). Guo et al (17) reported that tumor suppressor SOX7 functions as an independent checkpoint for beta-catenin transcriptional activity in PCa .…”