Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors
Abstract DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prog...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46484-3 |
| _version_ | 1797630227304677376 |
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| author | Fatemeh Tajik Fahimeh Fattahi Fereshteh Rezagholizadeh Behnaz Bouzari Pegah Babaheidarian Masoud Baghai Wadji Zahra Madjd |
| author_facet | Fatemeh Tajik Fahimeh Fattahi Fereshteh Rezagholizadeh Behnaz Bouzari Pegah Babaheidarian Masoud Baghai Wadji Zahra Madjd |
| author_sort | Fatemeh Tajik |
| collection | DOAJ |
| description | Abstract DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies. |
| first_indexed | 2024-03-11T11:05:12Z |
| format | Article |
| id | doaj.art-43e1f5f4113141e1a4ddfb3004743393 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:05:12Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-43e1f5f4113141e1a4ddfb30047433932023-11-12T12:14:49ZengNature PortfolioScientific Reports2045-23222023-11-0113111910.1038/s41598-023-46484-3Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumorsFatemeh Tajik0Fahimeh Fattahi1Fereshteh Rezagholizadeh2Behnaz Bouzari3Pegah Babaheidarian4Masoud Baghai Wadji5Zahra Madjd6Oncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesDepartment of Pathology, School of Medicine, Iran University of Medical SciencesDepartment of Pathology, School of Medicine, Iran University of Medical SciencesDepartment of Surgery, Firoozgar Hospital, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical SciencesAbstract DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.https://doi.org/10.1038/s41598-023-46484-3 |
| spellingShingle | Fatemeh Tajik Fahimeh Fattahi Fereshteh Rezagholizadeh Behnaz Bouzari Pegah Babaheidarian Masoud Baghai Wadji Zahra Madjd Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors Scientific Reports |
| title | Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors |
| title_full | Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors |
| title_fullStr | Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors |
| title_full_unstemmed | Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors |
| title_short | Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors |
| title_sort | nuclear overexpression of dna damage inducible transcript 4 ddit4 is associated with aggressive tumor behavior in patients with pancreatic tumors |
| url | https://doi.org/10.1038/s41598-023-46484-3 |
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