Author:
Sajadi Manizheh,Fazilti Mohammad,Nazem Habibollah,Mahdevar Mohammad,Ghaedi Kamran
Abstract
Abstract
Introduction
Transcription factors (TFs) are essential for many biological processes and regulate the expression of several genes. This study’s objective was to analyze the abnormalities in TF expression, their impact on patient prognosis, and related pathways in colorectal cancer (CRC).
Method
The expression alterations of all TFs were investigated using the cancer genome atlas and GSE39582 data. Clinical data were also used to study the association between TFs expression and patient prognosis through the Cox regression test, and a predictive model of CRC patient survival was constructed based on TFs expression. Co-expression network was used to discover TF-related pathways. To validate the findings, the RT-qPCR method was applied to CRC samples and adjacent normal tissue.
Results
The findings revealed that ANKZF1, SALL4, SNAI1, TIGD1, LEF1, FOXS1, SIX4, and ETV5 expression levels increased in both cohorts and were linked to the poor prognosis. NR3C2, KLF4, CASZ1, FOXD2, ATOH1, SALL1, and RORC expression, on the other hand, exhibited a significant decrease, and their increase was related to the good prognosis of patients. The patient mortality risk model based on expression of mentioned TFs revealed that, independent of clinical characteristics, the expression of ANKZF1, LEF1, CASZ1, and ATOH1 could accurately predict patient survival rates. According to the co-expression network, increased transcription factors were linked to metastatic pathways, while decreasing TFs were involved to apoptotic pathways. RT-qPCR findings showed that FOXS1 expression was markedly overexpressed in CRC samples. However, in CRC samples, the expression of CASZ1 decreased.
Conclusion
In CRC, TFs expression of ANKZF1, LEF1, CASZ1 and ATOH1 are deregulated, which are associated with prognosis in patients. According to our findings, changes in the expression of the mentioned TFs have the potential to be considered diagnostic and prognostic biomarkers for CRC patients.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference26 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209–49.
2. Birkenkamp-Demtroder K, Christensen LL, Olesen SH, Frederiksen CM, Laiho P, Aaltonen LA, et al. Gene expression in colorectal cancer. Cancer Res. 2002;62(15):4352–63.
3. Lin Y-H, Friederichs J, Black MA, Mages J, Rosenberg R, Guilford PJ, et al. Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res. 2007;13(2):498–507.
4. Brzozowa M, Michalski M, Wyrobiec G, Piecuch A, Dittfeld A, Harabin-Słowińska M, et al. The role of Snail1 transcription factor in colorectal cancer progression and metastasis. Contemp Oncol. 2015;19(4):265.
5. Lindner P, Paul S, Eckstein M, Hampel C, Muenzner JK, Erlenbach-Wuensch K, et al. EMT transcription factor ZEB1 alters the epigenetic landscape of colorectal cancer cells. Cell Death Dis. 2020;11(2):1–13.