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

被引：26

作者：

Biswas, Partha ^{[1
,2
,3
]}

Dey, Dipta ^{[4
]}

Rahman, Atikur ^{[1
,5
]}

Islam, Md. Aminul ^{[1
,4
]}

Susmi, Tasmina Ferdous ^{[1
]}

Kaium, Md. Abu ^{[1
]}

Hasan, Md. Nazmul ^{[3
]}

Rahman, MD. Hasanur ^{[2
,6
]}

Mahmud, Shafi ^{[7
]}

Saleh, Md. Abu ^{[7
]}

Paul, Priyanka ^{[4
]}

Rahman, Md Rezanur ^{[8
]}

Saber, Md. Al ^{[9
]}

Song, Hangyeul ^{[10
]}

Rahman, Md. Ataur ^{[10
,11
,12
]}

Kim, Bonglee ^{[10
,11
]}

机构：

[1] Jashore Univ Sci & Technol JUST, Fac Biol Sci & Technol, Dept Genet Engn & Biotechnol, Jashore 7408, Bangladesh

[2] ABEx Bio Res Ctr, East Azampur, Dhaka 1230, Bangladesh

[3] Jashore Univ Sci & Technol JUST, Fac Biol Sci & Technol, Dept Genet Engn & Biotechnol, Lab Pharmaceut Biotechnol & Bioinformat, Jashore 7408, Bangladesh

[4] Bangabandhu Sheikh Mujibur Rahman Sci & Technol U, Fac Life Sci, Dept Biochem & Mol Biol, Gopalgonj 8100, Bangladesh

[5] Jiangnan Univ, Sch Biotechnol, Fermentat Engn, Wuxi 214122, Jiangsu, Peoples R China

[6] Bangabandhu Sheikh Mujibur Rahman Sci & Technol U, Dept Biotechnol & Genet Engn, Gopalganj 8100, Bangladesh

[7] Rajshahi Univ, Dept Genet Engn & Biotechnol, Rajshahi 6205, Bangladesh

[8] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[9] Univ Pecs, Sch Med, Biotechnol, H-7624 Pecs, Hungary

[10] Kyung Hee Univ, Dept Pathol, Coll Korean Med, 26 Kyungheedae Ro, Seoul 02447, South Korea

[11] Kyung Hee Univ, Coll Korean Med, Korean Med Based Drug Repositioning Canc Res Ctr, Seoul 02447, South Korea

[12] Islam Univ, Fac Biol Sci, Dept Biotechnol & Genet Engn, Global Biotechnol Biomed Res Network GBBRN, Kushtia 7003, Bangladesh

来源：

JOURNAL OF PERSONALIZED MEDICINE | 2021年 / 11卷 / 09期

基金：

新加坡国家研究基金会;

关键词：

SYK gene; onco-informatics; colorectal cancer; biomarker; molecular dynamics simulation; colorectal adenocarcinoma; PROTEIN-TYROSINE KINASE; MOLECULAR-DYNAMICS; BREAST-CANCER; TUMOR-SUPPRESSOR; EXPRESSION; PROMOTER; DOCKING; IDENTIFICATION; METHYLATION; METASTASIS;

D O I：

10.3390/jpm11090888

中图分类号：

R19 [保健组织与事业（卫生事业管理）];

学科分类号：

摘要：

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.

引用

页数：24