scholarly journals 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

2021 ◽  
Vol 11 (9) ◽  
pp. 888
Author(s):  
Partha Biswas ◽  
Dipta Dey ◽  
Atikur Rahman ◽  
Md. Aminul Islam ◽  
Tasmina Ferdous Susmi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
In Silico ◽  
Prognostic Biomarker ◽  
Therapeutic Option ◽  
Genetic Alterations ◽  
Receptor Protein ◽  
Cancer Type ◽  
Syk Kinase ◽  
Potential Biomarker

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.

scholarly journals Evaluation of SYK Gene as a Prognostic Biomarker and Suggested Aromatic Potential Phytochemicals to Halt the Colorectal Cancer

2021 ◽  
Author(s):  
Partha Biswas ◽  
Dipta Dey ◽  
Atikur Rahman ◽  
Md. Aminul Islam ◽  
Tasmina Ferdous Susmi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Drug Repositioning ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Gene Encoding ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
Potential Biomarker

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

Cancer-type OATP1B3 mRNA has the potential to become a detection and prognostic biomarker for human colorectal cancer

2017 ◽  
Vol 11 (8) ◽  
pp. 629-639 ◽  
Author(s):  
Yuchen Sun ◽  
Manami Harada ◽  
Osamu Shimozato ◽  
Hiroaki Souda ◽  
Nobuhiro Takiguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Biomarker ◽  
Cancer Type ◽  
Human Colorectal Cancer

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110150
Author(s):  
Gang Li ◽  
Wei Zhou ◽  
Xiurong Zhao ◽  
Ying Xie
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Herbal Remedies ◽  
Receptor Protein ◽  
Stable Complex ◽  
Traditional Chinese Medicines ◽  
Ligand Interaction ◽  
Chinese Medicines ◽  
In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

scholarly journals Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

2021 ◽  
Author(s):  
B. González Astorga ◽  
F. Salvà Ballabrera ◽  
E. Aranda Aguilar ◽  
E. Élez Fernández ◽  
P. García-Alfonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Option ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Effective Therapeutic Option ◽  
Line Setting ◽  
First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Xi Jiao ◽  
Xin Wei ◽  
Shuang Li ◽  
Chang Liu ◽  
Huan Chen ◽  
...  
Keyword(s):  
Gastrointestinal Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Cancer Center ◽  
Genomic Profile ◽  
Prognostic Signature ◽  
Powerful Predictor ◽  
Potential Biomarker ◽  
Peking University

AbstractThe association between genetic variations and immunotherapy benefit has been widely recognized, while such evidence in gastrointestinal cancer remains limited. We analyzed the genomic profile of 227 immunotherapeutic gastrointestinal cancer patients treated with immunotherapy, from the Memorial Sloan Kettering (MSK) Cancer Center cohort. A gastrointestinal immune prognostic signature (GIPS) was constructed using LASSO Cox regression. Based on this signature, patients were classified into two subgroups with distinctive prognoses (p < 0.001). The prognostic value of the GIPS was consistently validated in the Janjigian and Pender cohort (N = 54) and Peking University Cancer Hospital cohort (N = 92). Multivariate analysis revealed that the GIPS was an independent prognostic biomarker. Notably, the GIPS-high tumor was indicative of a T-cell-inflamed phenotype and immune activation. The findings demonstrated that GIPS was a powerful predictor of immunotherapeutic survival in gastrointestinal cancer and may serve as a potential biomarker guiding immunotherapy treatment decisions.

scholarly journals Potential treatment for chronic myeloid leukemia using microRNA: in silico comparison between plants and human microRNAs in targeting BCR-ABL1 gene

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Syarifah Faezah Syed Mohamad ◽  
Marjanu Hikmah Elias
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Pathway Analysis ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Interaction Network ◽  
Folding Energy

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the expression of the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) are used to treat CML, but mutations in the tyrosine kinase domain contribute to CML chemo-resistance. Therefore, finding alternative molecular-targeted therapy is important for the comprehensive treatment of CML. MicroRNAs (miRNA) are small non-coding regulatory RNAs which suppress the expression of their target genes by binding to the 3′ untranslated region (3′UTR) of the target mRNA. Hypothetically, the miRNA-mRNA interaction would suppress BCR-ABL1 expression and consequently reduce and inhibit CML cell proliferation. Thus, our objective was to determine the target interaction of human and plant miRNAs targeting the 3′UTR region of BCR-ABL1 in terms of miRNA binding conformity, protein interaction network, and pathways using in silico analysis. The 3′UTR sequence of BCR-ABL1 is obtained from Ensembl Genome Browser while the binding conformity was determined using the PsRNATarget Analysis Server, RNA22, Target Rank Server, and DIANA TOOLS. Protein-protein interaction network and pathway analysis are determined using STRING, Cytoscape, and KEGG pathway analysis. Results Five plants and five human miRNAs show strong binding conformity with 3′UTR of BCR-ABL1. The strongest binding conformity was shown by Oryza sativa’s Osa-miR1858a and osa-miR1858b with −24.4 kcal/mol folding energy and a p value of 0.0077. Meanwhile, in human miRNA, the hsa-miR-891a-3p shows the highest miTG score of 0.99 with −12 kcal/mol folding energy and a p value of 0.037. Apart from ABL1, osa-miR1858a/osa-miR1858b and hsa-miR891a-3p also target other 720 and 645 genes, respectively. The interaction network of Osa-miR1858a/osa-miR1858b and hsa-miR891a-3p identifies nineteen and twelve ABL1’s immediate neighboring proteins, respectively. The pathways analysis focuses on the RAS, MAPK, CML, and hematopoietic cell lineage pathway. Conclusion Both plant and human miRNAs tested in this study could be a potential therapeutic prospect in CML treatment, but thermodynamically, osa-miR1858a/osa-miR1858b binding to ABL1 is more favorable. However, it is important to carry out more research in vitro and in vivo and clinical studies to assess its efficacy as a targeted therapy for CML. Graphical abstract

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