Decreased expression of Sox7 correlates with the upregulation of the Wnt/β-catenin signaling pathway and the poor survival of gastric cancer patients

Abstract

Sox7 is a tumor suppressor gene that plays an important role in the inhibition and progression of cancer. In the present study, we sought to investigate Sox7 expression in gastric cancer (GC) and its association with the Wnt/β-catenin signaling pathway. We also wished to determine its clinicopathological significance and prognostic implications. Sox7 expression and its effects on the Wnt/β-catenin signaling in vitro were assessed by reverse transcription-polymerase chain reaction using the AGS, MKN-45 and GES-1 gastric cell lines. We also used immunohistochemistry on paraffin-embedded tissue samples and western blot analysis on fresh tissue samples from patients with GC. The results revealed that Sox7 expression was significantly lower in the GC samples than in distal normal tissues, which was in accordance with our results obtained from our in vitro experiments on the cell lines. However, the expression levels of β-catenin were significantly higher. Sox7 and β-catenin expression significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and the TNM stage. Patient samples that were Sox7-negative correlated with a significantly shorter survival time. Multivariate survival analysis revealed that Sox7 and β-catenin had an independent effect on the survival of GC patients. Sox7 and β-catenin expression in GC had a negative liner correlation with each other. Our findings suggest that Sox7 plays an important role in inhibiting tumorigenesis and progression, and may be a potential marker for predicting the prognosis of patients with GC.

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

“…SOX7, a member of the high-mobility group (HMG) transcription factor family, functions as an indispensable co-receptor and plays a critical role in the activation of the canonical Wnt/β-catenin signaling pathway [13,16]. SOX7 is reported to have a tumor-suppressive function in cancers [17,18].…”

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…These molecular changes seem to be required to drive early carcinogenesis events in the stomach, a hypothesis that is supported by studies showing that GSK3b phosphorylation and inactivation is associated with cancer progression in gastric cancer [105] . Different studies have shown downregulation-in occasion by unspecified mechanisms-of various negative regulators of the Wnt/b-catenin signaling involved in proliferation and invasion in gastric cancer, including sFRP, Sox7, Sox10, Sox17, HSulf-1, RACK1, ZNRF3 and OSR1 [78,[106][107][108][109][110][111][112][113] . Some Wnt-target genes, such as Dkk-1, Axin, Nemo kinase, etc., have shown to cause inhibition of Wnt signaling itself [114,115] .…”

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

“…The generation of differential expression profiles from pathological samples can markedly improve cancer biomarker discovery (2). In a previous study, it was demonstrated that Sox7 and β-catenin expression significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis and the TNM (tumor, node and metastasis) stage in GC (3). Overexpression of zinc finger, DHHC-type containing 14 (ZDHHC14) promotes the migration and invasion of scirrhous GC (4).…”

“…Ras association domain family member 10 (RASSF10) is an epigenetically silenced tumor suppressor in GC (6). It has previously been demonstrated that the inactivation of tumor suppressor genes and activation of oncogenes serve a significant role in carcinogenesis (3)(4)(5)(6). However, the etiology of GC remains poorly understood.…”