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Published on: September 18, 2020
Lower cytoplasmic expression of DDIT4 is associated with poor prognosis in gastric cancer patients
Masoumeh Dehghan Manshadi1,2, Fatemeh Tajik1,3, Leili Saeednejad Zanjani1,4
1Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Introduction:
DNA damage-inducible transcript 4 (DDIT4), also known as Redd1, Dig2, and RTP801 was identified to be upregulated in response to a variety of cellular stresses, including DNA damage, endoplasmic reticulum stress, and energy stress. Several studies have discovered that dysregulation of DDIT4 involved in various cancers with paradoxical expression and roles. Hence, this study was designed to investigate the clinical significance and prognostic value of DDIT4 in different subtypes of gastric cancer (GC).
Materials And Methods:
To evaluate the expression pattern of DDIT4 in GC tissues as well as adjacent normal tissue, we utilized immunohistochemistry on tissue microarray (TMA) slides.
Results:
Our findings revealed that nuclear expression of DDIT4 was higher in GC tissues than in non-malignant samples. Also, the cytoplasmic and membranous expression of DDIT4 were significantly lower in tumor samples (P = 0.007 and P = 0.002, respectively). The results indicated that there was a statistically significant association between low cytoplasmic and membranous expression of DDIT4 and advanced histological grade (P = 0.001 and P = 0.016). The survival analysis revealed that lowered cytoplasmic expression of DDIT4 is significantly associated with worse DSS (P = 0.038).
Conclusion:
Lower cytoplasmic expression of DDIT4 could serve as a promising prognostic biomarker in GC.
Insights
Lower cytoplasmic expression of DNA damage-inducible transcript 4 (DDIT4) is linked to poorer outcomes in gastric cancer (GC). This finding suggests DDIT4 may be a valuable prognostic biomarker for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- DNA damage-inducible transcript 4 (DDIT4), also known as Redd1, is implicated in cellular stress responses.
- Dysregulation of DDIT4 has been observed in various cancers, exhibiting paradoxical roles.
- The clinical significance of DDIT4 in gastric cancer (GC) subtypes requires further investigation.
Purpose of the Study:
- To investigate the clinical significance of DDIT4 expression in gastric cancer.
- To evaluate the prognostic value of DDIT4 in different subtypes of GC.
Main Methods:
- Immunohistochemistry was performed on tissue microarray (TMA) slides.
- DDIT4 expression patterns were analyzed in GC tissues and adjacent normal tissues.
Main Results:
- Nuclear DDIT4 expression was elevated in GC tissues compared to non-malignant samples.
- Cytoplasmic and membranous DDIT4 expression were significantly lower in tumor samples.
- Low cytoplasmic DDIT4 expression correlated with advanced histological grade and worse disease-specific survival (DSS) in GC.
Conclusions:
- Reduced cytoplasmic expression of DDIT4 serves as a potential prognostic biomarker for gastric cancer.
- DDIT4 warrants further study as a predictive marker for GC patient outcomes.
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