Overexpression of GDP dissociation inhibitor 1 gene associates with the invasiveness and poor outcomes of colorectal cancer

Bioengineered

Xiaolei Zhang¹  Jiemin Shi¹  Huajiang Lin¹  Xiao Xie¹  Pengtao Song²  Xiangyi He²  Jing Zhong³ 

[1] Department of Gastroenterology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Affiliated Huzhou Hospital Zhejiang University School of Medicine, Huzhou, Zhejiang Province, Chin;Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Affiliated Huzhou Hospital Zhejiang University School of Medicine, Huzhou, Zhejiang Province, Chin;Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Affiliated Huzhou Hospital Zhejiang University School of Medicine, Huzhou, Zhejiang Province, Chin;

关键词: GDP dissociation inhibitor 1;    colorectal cancer;    prognostic biomarker;   

DOI  :  10.1080/21655979.2021.1967031

来源: Taylor & Francis

【 摘 要 】

GDP dissociation inhibitor (GDI) regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting GDP dissociation. This study evaluated the potential prognostic and predictive value of GDI1 in colorectal cancer (CRC). To address the prognostic power of GDI1, we performed individual and pooled survival analyses on six independent CRC microarray gene expression datasets. GDI1-enriched signatures were also analyzed. Kaplan–Meier and Cox proportional analyses were employed for survival analysis. An immunohistochemistry (IHC) analysis was performed to validate the clinical relevance and prognostic significance of the GDI1 protein level in CRC tissue samples. The results revealed that GDI1 mRNA level was significantly linked with the aggressiveness of CRC, which is compatible with gene set enrichment analysis. A meta-analysis and pooled analysis demonstrated that a higher mRNA GDI1 expression was dramatically correlated with a worse survival in a dose-dependent manner in CRC patients. Further IHC analysis validated that the protein expression of GDI1 in both cytoplasm and membrane also significantly impacted the outcome of CRC patients. In CRC patients with stage III, chemotherapy significantly reduced the relative risk of death in low-GDI1 subgroup (hazard ratio (HR) = 0.22; 95% confidence interval (95% CI) 0.09–0.56, p = 0.0003), but not in high-GDI1 subgroup (HR = 0.63; 95% CI 0.35–1.14, p = 0.1137). Therefore, both high mRNA and protein levels of GDI1 were significantly related to poor outcomes in CRC patients. GD11 may serve as a prognostic biomarker for CRC.

【 授权许可】

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