The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis

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). Me...

Full description

Bibliographic Details
Main Authors: Manizheh Sajadi, Mohammad Fazilti, Habibollah Nazem, Mohammad Mahdevar, Kamran Ghaedi
Format: Article
Language:English
Published: BMC 2022-11-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-022-02751-3
_version_ 1827979400541372416
author Manizheh Sajadi
Mohammad Fazilti
Habibollah Nazem
Mohammad Mahdevar
Kamran Ghaedi
author_facet Manizheh Sajadi
Mohammad Fazilti
Habibollah Nazem
Mohammad Mahdevar
Kamran Ghaedi
author_sort Manizheh Sajadi
collection DOAJ
description 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.
first_indexed 2024-04-09T21:36:12Z
format Article
id doaj.art-cad5024fb2fc487690313438d2c94bfa
institution Directory Open Access Journal
issn 1475-2867
language English
last_indexed 2024-04-09T21:36:12Z
publishDate 2022-11-01
publisher BMC
record_format Article
series Cancer Cell International
spelling doaj.art-cad5024fb2fc487690313438d2c94bfa2023-03-26T11:18:11ZengBMCCancer Cell International1475-28672022-11-012211910.1186/s12935-022-02751-3The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysisManizheh Sajadi0Mohammad Fazilti1Habibollah Nazem2Mohammad Mahdevar3Kamran Ghaedi4Department of Biochemistry, Faculty of Science, Payame Noor UniversityDepartment of Biochemistry, Payame Noor UniversityDepartment of Biochemistry, Faculty of Science, Payame Noor UniversityGenius Gene, Genetics and Biotechnology CompanyDepartment of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of IsfahanAbstract 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.https://doi.org/10.1186/s12935-022-02751-3Gene expressionSurvival rateBiomarkersMaster genes
spellingShingle Manizheh Sajadi
Mohammad Fazilti
Habibollah Nazem
Mohammad Mahdevar
Kamran Ghaedi
The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
Cancer Cell International
Gene expression
Survival rate
Biomarkers
Master genes
title The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
title_full The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
title_fullStr The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
title_full_unstemmed The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
title_short The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
title_sort expression changes of transcription factors including ankzf1 lef1 casz1 and atoh1 as a predictor of survival rate in colorectal cancer a large scale analysis
topic Gene expression
Survival rate
Biomarkers
Master genes
url https://doi.org/10.1186/s12935-022-02751-3
work_keys_str_mv AT manizhehsajadi theexpressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT mohammadfazilti theexpressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT habibollahnazem theexpressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT mohammadmahdevar theexpressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT kamranghaedi theexpressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT manizhehsajadi expressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT mohammadfazilti expressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT habibollahnazem expressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT mohammadmahdevar expressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis
AT kamranghaedi expressionchangesoftranscriptionfactorsincludingankzf1lef1casz1andatoh1asapredictorofsurvivalrateincolorectalcanceralargescaleanalysis