OBJECTIVETo investigate the expression and clinical significance of G protein-coupled receptor 31 (GPR31) in colorectal cancer tissue.

METHODSCancer tissues and adjacent normal tissues of 321 cases with colorectal cancer confirmed by pathology and undergoing resection in the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were collected. The expression of GPR31 was examined by immunohistochemical staining. According to the expression level of GPR31 (A value=0.051), all the patients were divided into low GPR31 expression group and high GPR31 expression group. Clinicopathology and prognosis between the two groups were compared. Risk factors affecting prognosis were investigated.

RESULTSGPR31 expression was significantly higher in colorectal cancer tissues compared to adjacent normal tissues (mean A, 0.063±0.014 vs. 0.045±0.020, P<0.001). A total of 197 cancer tissue samples were defined as low expression and 124 as high expression. Significant difference was observed in the number of patient in pM classification between the two groups (P=0.007). High expression group had obviously higher distant metastasis rate than low expression group [12.1% (15/124) vs. 4.1% (8/197), P=0.007]. The 5-year survival rate and tumor-free survival rate were 84.3% and 82.2% in the low expression group, and both 59.7% in high expression group (all P<0.05). Multivariate analysis revealed elderly, abnormal CEA, lymphatic metastasis, distant metastasis and up-regulated GPR31 expression were independent risk factors of overall survival and disease-free survival in colorectal cancer patients (all P<0.05).

CONCLUSIONSGPR31 expression is significantly up-regulated in colorectal cancer tissues. High GPR31expression indicates poor prognosis of colorectal cancer, and may be used as a predictive marker.

Aged ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Disease-Free Survival ; Humans ; Lymphatic Metastasis ; Prognosis ; Receptors, G-Protein-Coupled ; metabolism ; Risk Factors ; Survival Rate ; Up-Regulation

Objective To investigate the expression and clinical significance of G protein-coupled receptor 31(GPR31) in colorectal cancer tissue. Methods Cancer tissues and adjacent normal tissues of 321 cases with colorectal cancer confirmed by pathology and undergoing resection in the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were collected. The expression of GPR31 was examined by immunohistochemical staining. According to the expression level of GPR31 (A value=0.051), all the patients were divided into low GPR31 expression group and high GPR31 expression group. Clinicopathology and prognosis between the two groups were compared. Risk factors affecting prognosis were investigated. Results GPR31 expression was significantly higher in colorectal cancer tissues compared to adjacent normal tissues (mean A, 0.063±0.014 vs. 0.045±0.020, P<0.001). A total of 197 cancer tissue samples were defined as low expression and 124 as high expression. Significant difference was observed in the number of patient in pM classification between the two groups (P=0.007). High expression group had obviously higher distant metastasis rate than low expression group [12.1%(15/124) vs. 4.1%(8/197), P=0.007]. The 5-year survival rate and tumor-free survival rate were 84.3% and 82.2% in the low expression group, and both 59.7% in high expression group (all P<0.05). Multivariate analysis revealed elderly, abnormal CEA, lymphatic metastasis, distant metastasis and up-regulated GPR31 expression were independent risk factors of overall survival and disease-free survival in colorectal cancer patients (all P<0.05). Conclusions GPR31 expression is significantly up-regulated in colorectal cancer tissues. High GPR31expression indicates poor prognosis of colorectal cancer, and may be used as a predictive marker.

Objective To investigate the expression and clinical significance of G protein-coupled receptor 31(GPR31) in colorectal cancer tissue. Methods Cancer tissues and adjacent normal tissues of 321 cases with colorectal cancer confirmed by pathology and undergoing resection in the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were collected. The expression of GPR31 was examined by immunohistochemical staining. According to the expression level of GPR31 (A value=0.051), all the patients were divided into low GPR31 expression group and high GPR31 expression group. Clinicopathology and prognosis between the two groups were compared. Risk factors affecting prognosis were investigated. Results GPR31 expression was significantly higher in colorectal cancer tissues compared to adjacent normal tissues (mean A, 0.063±0.014 vs. 0.045±0.020, P<0.001). A total of 197 cancer tissue samples were defined as low expression and 124 as high expression. Significant difference was observed in the number of patient in pM classification between the two groups (P=0.007). High expression group had obviously higher distant metastasis rate than low expression group [12.1%(15/124) vs. 4.1%(8/197), P=0.007]. The 5-year survival rate and tumor-free survival rate were 84.3% and 82.2% in the low expression group, and both 59.7% in high expression group (all P<0.05). Multivariate analysis revealed elderly, abnormal CEA, lymphatic metastasis, distant metastasis and up-regulated GPR31 expression were independent risk factors of overall survival and disease-free survival in colorectal cancer patients (all P<0.05). Conclusions GPR31 expression is significantly up-regulated in colorectal cancer tissues. High GPR31expression indicates poor prognosis of colorectal cancer, and may be used as a predictive marker.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.