Analysis of SYK gene as a prognostic biomarker and suggested potential bioactive phytochemicals as an alternative therapeutic option for colorectal cancer: An in-silico pharmaco-informatics investigation

Partha Biswas, Dipta Dey, Atikur Rahman, Md Aminul Islam, Tasmina Ferdous Susmi, Md Abu Kaium, Md Nazmul Hasan, Md Hasanur Rahman, Shafi Mahmud, Md Abu Saleh, Priyanka Paul, Md Rezanur Rahman, Md Al Saber, Hangyeul Song, Md Ataur Rahman, Bonglee Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background: SYK gene regulates the expression of SYK kinase (Spleen tyrosine kinase), an important non-receptor protein-tyrosine kinase for immunological receptor-mediated signaling, which is also considered a tumor growth metastasis initiator. An onco-informatics analysis was adopted to evaluate the expression and prognostic value of the SYK gene in colorectal cancer (CRC), the third most fatal cancer type; of late, it may be a biomarker as another targeted site for CRC. In addition, identify the potential phytochemicals that may inhibit the overexpression of the SYK kinase protein and minimize the human CRC. Materials & Methods: The differential expression of the SYK gene was analyzed using several transcriptomic databases, including Oncomine, UALCAN, GENT2, and GEPIA2. The server cBioPortal was used to analyze the mutations and copy number alterations, whereas GENT2, Gene Expression Profiling Interactive Analysis (GEPIA), Onco-Lnc, and PrognoScan were used to examine the survival rate. The protein-protein interaction network of SYK kinase and its co-expressed genes was conducted via Gene-MANIA. Considering the SYK kinase may be the targeted site, the selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. Molecular interactions were also observed by following the Ligplot+ version 2.2. YASARA molecular dynamics simulator was applied for the post-validation of the selected phytochemicals. Results: Our result reveals an increased level of mRNA expression of the SYK gene in colorectal adenocarcinoma (COAD) samples compared to those in normal tissues. A significant methylation level and various genetic alterations recurrence of the SYK gene were analyzed where the fluctuation of the SYK alteration frequency was detected across different CRC studies. As a result, a lower level of SYK expression was related to higher chances of survival. This was evidenced by multiple bioinformatics platforms and web resources, which demonstrated that the SYK gene can be a potential biomarker for CRC. In this study, aromatic phytochemicals, such as kaempferol and glabridin that target the macromolecule (SYK kinase), showed higher stability than the controls, and we have estimated that these bioactive potential phytochemicals might be a useful option for CRC patients after the clinical trial. Conclusions: Our onco-informatics investigation suggests that the SYK gene can be a potential prognostic biomarker of CRC. On the contrary, SYK kinase would be a major target, and all selected compounds were validated against the protein using in-silico drug design approaches. Here, more in vitro and in vivo analysis is required for targeting SYK protein in CRC.

Original languageEnglish
Article number888
JournalJournal of Personalized Medicine
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Biomarker
  • Colorectal adenocarcinoma
  • Colorectal cancer
  • Molecular dynamics simula-tion
  • Onco-informatics
  • SYK gene

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