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Published on: April 12, 2024
Downregulated expression of DIXDC1 in hepatocellular carcinoma and its correlation with prognosis
Senjun Zhou1, Jiliang Shen1, Shuang Lin1
1Key Laboratory of Endoscopic Technique Research of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, China.
Abstract:
Dishevelled-Axin domain containing 1 (DIXDC1) is a DIX (Dishevelled-Axin) domain possessing protein that acts as a positive regulator of the Wnt pathway. Although DIXDC1 has been investigated in several cancers, it has not yet been studied in human hepatocellular carcinoma (HCC). The purpose of the current study was to investigate the expression pattern of DIXDC1 and assess the clinical significance of DIXDC1 expression in HCC patients. Data containing three independent investigations from Oncomine database demonstrated that DIXDC1 mRNA was downregulated in HCC compared with matched non-cancerous tissues. Similar results were also obtained in 25 paired HCC tissues and corresponding non-cancerous tissues by qPCR and Western blot analysis. Additionally, another independent set of 140 pairs of HCC specimens was evaluated for DIXDC1 expression by IHC and demonstrated that reduced expression of DIXDC1 in 50.7 % (71/140) of HCC tissues was significantly correlated with tumor size (p = 0.024), tumor differentiation (p < 0.001), tumor thrombi (p = 0.019), TNM stage (p = 0.019), and BCLC stage (p = 0.008). Importantly, Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC patients and found that DIXDC1 protein expression was one of the independent prognostic factors for overall survival of HCC patients.
Insights
Dishevelled-Axin domain containing 1 (DIXDC1) is downregulated in hepatocellular carcinoma (HCC). Reduced DIXDC1 expression correlates with advanced HCC features and predicts poor patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Dishevelled-Axin domain containing 1 (DIXDC1) is a key regulator of the Wnt pathway.
- DIXDC1's role in hepatocellular carcinoma (HCC) remains unexplored.
Purpose of the Study:
- To investigate DIXDC1 expression patterns in HCC.
- To assess the clinical significance and prognostic value of DIXDC1 in HCC patients.
Main Methods:
- Analysis of DIXDC1 mRNA expression using the Oncomine database.
- Quantitative PCR (qPCR) and Western blot analysis on paired HCC tissues.
- Immunohistochemistry (IHC) evaluation of DIXDC1 protein in 140 HCC specimens.
- Kaplan-Meier survival and Cox regression analyses for prognostic assessment.
Main Results:
- DIXDC1 mRNA was significantly downregulated in HCC tissues compared to non-cancerous tissues.
- Reduced DIXDC1 protein expression was observed in 50.7% of HCC cases.
- Lower DIXDC1 expression correlated significantly with larger tumor size, poor differentiation, presence of tumor thrombi, advanced TNM stage, and higher BCLC stage.
- DIXDC1 protein expression emerged as an independent prognostic factor for overall survival in HCC patients.
Conclusions:
- DIXDC1 is downregulated in human HCC.
- DIXDC1 expression is clinically significant and serves as a potential independent prognostic biomarker for HCC patients.
- Further research into DIXDC1's role in HCC pathogenesis is warranted.

