PTH-100 DAP3 and the DAP3 Binding Cell Death Enhancer-1 (DELE1) in human colorectal cancer

• Published in: Gut Vol. 70; no. Suppl 4; p. A163
• Main Authors: Sui, Laijian, Zeng, Jianyuan, Ye, Lin, Sanders, Andrew J, Zhao, Huishan, Jiang, Aihua, Zhu, Jinkui, Song, Xicheng, Hargest, Rachel, Jiang, Wen G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 07.11.2021; BMJ Publishing Group LTD
• Subjects: Apoptosis; Breast cancer; Cancer; Cell death; Cellular stress response; Colorectal cancer; Colorectal carcinoma; Gene expression; Immunohistochemistry; Leukemia; Lymph nodes; Medical prognosis; Mitochondria; Parathyroid hormone; Patients; Polymerase chain reaction; Proteins; Solid tumors; Transcription; Tumors; γ-Interferon
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2021-BSG.303

IntroductionDeath association protein-3 (DAP3) was discovered as a responsive protein to interferon-gamma induced cell death and may exert this regulation by interacting with DELE1 (DAP3 Binding Cell Death Enhancer 1) (also known as KIAA0141), a newly discovered mitochondrial stress protein in response to cell stress signals. Whilst DAP3 has been shown to be aberrantly expressed in a limited number of solid tumours, eg. breast cancer and in haematological malignancies (leukaemia), little is known about the relationship between DAP3 and DELE1 in other solid cancers. The present study examined the expression levels of both DAP3 and in DELE1 in colorectal cancers.MethodsA cohort of colorectal tissues from ninety four patients were collected after surgery. Gene transcript levels of both DAP3 and DELE1 were quantitatively assessed by real time polymerase chain reaction. DAP3 and DELE1 proteins in normal colon and tumour tissues were evaluated by immunohistochemistry on tissue arrays. Patients’ clinical, pathological and outcome information were collected and evaluated against gene expression levels.ResultsColorectal tumours had significantly higher levels of DAP3 than normal colon tissues (p<0.001) but DELE1 did not show a difference between tumour and normal tissues. Levels of DAP3 and DELE1 had significant association with disease free survival (p<0.001 and p=0.043) and overall survival (p=0.006 and p=0.068 respectively). Levels of both DAP3 and DELE1 were seen to markedly differ between patients who developed recurrence from those who did not. Kaplan Meier models showed a significant difference for both DAP3 and DELE1 in time to recurrence. Neither DAP3 nor DELE1 had differing levels in tumours with or without lymph node involvement. An interesting feature of the expression pattern of both DAP3 and DELE1 was that they significantly correlated in normal colorectal tissues (r=0.732, p<0.0001) but the correlation of expression was not seen in tumour tissues (p<0.05). Collectively, DAP3 (p=0.002) and DELE1 (p=0.01), together with T staging (p=0.024) are independent prognostic indicators for the overall survival of the patients. DAP3 (p=0.001), together with TNM staging (p=0.003), Dukes staging (p=0.026) and Nodal status (p=0.024) are also independent predictors of the disease free survival of patients.ConclusionDeath associated protein DAP3 and its binding protein DELE1 are highly aberrant in colorectal cancers and are prognostic factors for patients’ clinical outcomes including overall and disease free survival and indicators for local recurrence.