Colorectal cancer (CRC) is a significant global health burden that ranks as the third most diagnosed and second most common cause of cancer related deaths worldwide. New therapeutic strategies include chemoprevention and use of molecules which could prevent, suppress or reverse CRC progression such as sulforaphane (SFN). However, evidences about its safety in CRC patients are still lacking. The aim of this in silico investigation was to predict SFN-induced adverse effects in CRC patients by computational analysis. The study showed that 334 genes were consistently dysregulated in CRC (223 downregulated and 111 upregulated), while 38 were recognized as significant and might be used as predictive biomarkers for overall survival and metastasis (TCGA, GEO, R studio). Among them, SFN interacted with 86 genes, out of which 11 were marked as significant (correlate with overall prognosis and metastasis). Sulforaphane potentiates the overexpression of TIMP1, AURKA, and CEP55, and promotes inhibi...tion of CRYAB, PLCE1, and MMP28, that might lead to the progression of CRC (CTD). Pathway enrichment analysis revealed that SFN stimulated Transcriptional activation of RUNX2, AURKA activation by TPX2, IL-10 signaling, while inhibited Differentiation of White and Brown Adipocyte process, an underlying pathway which inactivation led to obesity (Cytoscape ClueGo + CluePedia, DAVID). Thus, genome signature of CRC patients could serve as important factor when addressing the risk-to-benefit profile of SFN. Patients with colon cancer and increased expression of TIMP1, CCL20, SPP1, AURKA, CEP55, NEK2, SOX9 and CDK1, or downregulation of CRYAB, PLCE1, MMP28, BMP2 and PLAC8 may not be ideal candidates for SFN chemoprevention.
Keywords:
Toxicogenomic data mining / Adverse effects / Colon cancer / Differentially expressed genes / Sulforaphane
Source:
Biomedicine and Pharmacotherapy, 2021, 146
Publisher:
Elsevier Masson s.r.l.
Funding / projects:
“Improving anti-cancer
immunotherapy efficacy of CAR-T cells or PD-1/PD-L1 inhibitors by
combining immune modulators”, funded by the Ministry of Education,
Science and Technological Development of the Republic of Serbia, in the
framework of scientific cooperation with the People’s Republic of China
(451-03-1203/2021-09)
State’s Key Project of Research and
Development Plan of the People’s Republic of China (No. 2021YFE0110600)
TY - JOUR
AU - Bozić, Dragica
AU - Baralić, Katarina
AU - Živančević, Katarina
AU - Antonijević-Miljaković, Evica
AU - Ćurčić, Marijana
AU - Antonijević, Biljana
AU - Buha-Đorđević, Aleksandra
AU - Bulat, Zorica
AU - Zhang, Yi
AU - Yang, Li
AU - Đukić-Ćosić, Danijela
PY - 2021
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4018
AB - Colorectal cancer (CRC) is a significant global health burden that ranks as the third most diagnosed and second most common cause of cancer related deaths worldwide. New therapeutic strategies include chemoprevention and use of molecules which could prevent, suppress or reverse CRC progression such as sulforaphane (SFN). However, evidences about its safety in CRC patients are still lacking. The aim of this in silico investigation was to predict SFN-induced adverse effects in CRC patients by computational analysis. The study showed that 334 genes were consistently dysregulated in CRC (223 downregulated and 111 upregulated), while 38 were recognized as significant and might be used as predictive biomarkers for overall survival and metastasis (TCGA, GEO, R studio). Among them, SFN interacted with 86 genes, out of which 11 were marked as significant (correlate with overall prognosis and metastasis). Sulforaphane potentiates the overexpression of TIMP1, AURKA, and CEP55, and promotes inhibition of CRYAB, PLCE1, and MMP28, that might lead to the progression of CRC (CTD). Pathway enrichment analysis revealed that SFN stimulated Transcriptional activation of RUNX2, AURKA activation by TPX2, IL-10 signaling, while inhibited Differentiation of White and Brown Adipocyte process, an underlying pathway which inactivation led to obesity (Cytoscape ClueGo + CluePedia, DAVID). Thus, genome signature of CRC patients could serve as important factor when addressing the risk-to-benefit profile of SFN. Patients with colon cancer and increased expression of TIMP1, CCL20, SPP1, AURKA, CEP55, NEK2, SOX9 and CDK1, or downregulation of CRYAB, PLCE1, MMP28, BMP2 and PLAC8 may not be ideal candidates for SFN chemoprevention.
PB - Elsevier Masson s.r.l.
T2 - Biomedicine and Pharmacotherapy
T1 - Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation
VL - 146
DO - 10.1016/j.biopha.2021.112598
ER -
@article{
author = "Bozić, Dragica and Baralić, Katarina and Živančević, Katarina and Antonijević-Miljaković, Evica and Ćurčić, Marijana and Antonijević, Biljana and Buha-Đorđević, Aleksandra and Bulat, Zorica and Zhang, Yi and Yang, Li and Đukić-Ćosić, Danijela",
year = "2021",
abstract = "Colorectal cancer (CRC) is a significant global health burden that ranks as the third most diagnosed and second most common cause of cancer related deaths worldwide. New therapeutic strategies include chemoprevention and use of molecules which could prevent, suppress or reverse CRC progression such as sulforaphane (SFN). However, evidences about its safety in CRC patients are still lacking. The aim of this in silico investigation was to predict SFN-induced adverse effects in CRC patients by computational analysis. The study showed that 334 genes were consistently dysregulated in CRC (223 downregulated and 111 upregulated), while 38 were recognized as significant and might be used as predictive biomarkers for overall survival and metastasis (TCGA, GEO, R studio). Among them, SFN interacted with 86 genes, out of which 11 were marked as significant (correlate with overall prognosis and metastasis). Sulforaphane potentiates the overexpression of TIMP1, AURKA, and CEP55, and promotes inhibition of CRYAB, PLCE1, and MMP28, that might lead to the progression of CRC (CTD). Pathway enrichment analysis revealed that SFN stimulated Transcriptional activation of RUNX2, AURKA activation by TPX2, IL-10 signaling, while inhibited Differentiation of White and Brown Adipocyte process, an underlying pathway which inactivation led to obesity (Cytoscape ClueGo + CluePedia, DAVID). Thus, genome signature of CRC patients could serve as important factor when addressing the risk-to-benefit profile of SFN. Patients with colon cancer and increased expression of TIMP1, CCL20, SPP1, AURKA, CEP55, NEK2, SOX9 and CDK1, or downregulation of CRYAB, PLCE1, MMP28, BMP2 and PLAC8 may not be ideal candidates for SFN chemoprevention.",
publisher = "Elsevier Masson s.r.l.",
journal = "Biomedicine and Pharmacotherapy",
title = "Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation",
volume = "146",
doi = "10.1016/j.biopha.2021.112598"
}
Bozić, D., Baralić, K., Živančević, K., Antonijević-Miljaković, E., Ćurčić, M., Antonijević, B., Buha-Đorđević, A., Bulat, Z., Zhang, Y., Yang, L.,& Đukić-Ćosić, D.. (2021). Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation. in Biomedicine and Pharmacotherapy
Elsevier Masson s.r.l.., 146.
https://doi.org/10.1016/j.biopha.2021.112598
Bozić D, Baralić K, Živančević K, Antonijević-Miljaković E, Ćurčić M, Antonijević B, Buha-Đorđević A, Bulat Z, Zhang Y, Yang L, Đukić-Ćosić D. Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation. in Biomedicine and Pharmacotherapy. 2021;146.
doi:10.1016/j.biopha.2021.112598 .
Bozić, Dragica, Baralić, Katarina, Živančević, Katarina, Antonijević-Miljaković, Evica, Ćurčić, Marijana, Antonijević, Biljana, Buha-Đorđević, Aleksandra, Bulat, Zorica, Zhang, Yi, Yang, Li, Đukić-Ćosić, Danijela, "Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation" in Biomedicine and Pharmacotherapy, 146 (2021),
https://doi.org/10.1016/j.biopha.2021.112598 . .
