Comparative study of positive and negative sulforaphane activity against different tumor types via bioinformatic analysis

Abstract

Sulforaphane (SFN) is a compound found in cruciferous vegetables which have been studied as a molecule with the potential in disease prevention and treatment. SFN has demonstrated effectiveness against cancer. However, further research is needed to enhance the understanding of its pharmaco-toxicology profile in different cancer types. Thus, bioinformatics analysis was conducted to determine potential positive and negative SFN activity in 6 cancer varieties: breast, bladder, colorectal adenocarcinoma, lung, ovarium, and pancreatic cancer. Cancer-genome data were downloaded from The Cancer Genome Atlas Program database (TCGA) and further analyzed with R software. SFN-interacting genes were obtained from Comparative Toxicogenomic Database (CTD). Online tools such as jvenn, shinyGO, TIMER, and CTD were used for gene enrichment analysis and for examining the nature of SFN interactions with genes dysregulated in the investigated cancer types. CFP was the only gene significantly downregulated in all cancer tissues and linked to SFN. Its repression leads to the inhibition of apoptosis. SFN increases CFP expression and, thus, reactivates the apoptotic process. Among 7 upregulated genes in pancreatic cancer, SFN interacted with one, TSPAN1, by silencing its expression. TSPAN1 suppression was linked to the inhibition of cancer progression and better overall survival in patients with pancreatic cancer. A total of 55 genes significantly upregulated in the other 5 cancer types interacted with SFN. Survival analysis revealed that high PLK expression in lung cancer correlates with better overall survival, while SFN decreased its expression. On the contrary, high ADAM8 and C1QTNF6 expression negatively correlate with survival; SFN further increased ADAM8 expression but decreased C1QTNF6 expression. Next, SFN-interacting genes downregulated in breast cancer were enriched for dilatated and hypertrophic cardiomyopathy pathways, as well as lipid metabolism and atherosclerosis. Similarly, in bladder cancer, SFN interacted with 263 downregulated genes involved in dilatated and hypertrophic cardiomyopathy and metabolic disorders such as insulin resistance. In colorectal adenocarcinoma, repressed SFN-linked genes were related to arrhythmogenic right ventricular cardiomyopathy, metabolism of arachidonic acid, and again metabolic pathways. Similar results were obtained for lung and ovarian cancer indicating that SFN should be recommended with caution to patients with a history of cardiovascular disorders. In pancreatic cancer, a set of SFN-interacting downregulated genes was linked to immune-system pathways such as the chemokine signaling pathway, TNF signaling, and B cell receptor signaling. Therefore, although SFN shows positive antitumor activity, evaluation of genome signature in cancer patients may be an important factor for assessing the risk-to-benefit ratio of SFN treatment.