Browsing by Author "Khan, Walizeb"
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Publication Effect of MHC linked 7-gene signature on delayed hepatocellular carcinoma recurrence(Mdpi, 2021-10-28) Tariq, Fomaz; Khan, Walizeb; Ahmad, Washaakh; Riaz, Syeda Kiran; Khan, Mahvish; Sherwani, Subuhi; Haque, Shafiul; Malik, Muhammad Faraz Arshad; Iftikhar, Muhammad Jahangir; Khan, Saif; Haq, Farhan; Haque, Shafiul; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-2989-121X; AAN-2946-2020Dysregulated immune response significantly affects hepatocellular carcinoma's (HCC) prognosis. Human Leukocyte Antigens are key in devising immune responses against HCC. Here, we investigated how HLAs modulate HCC development at the transcriptomic level. RNA-seq data of 576 patients from two independent cohorts was retrieved. The clinicopathological relevance of all HLA genes was investigated using Fisher-Exact, correlation, and Kaplan-Meier and cox regression survival tests. Clustering of ~800 immune-related genes against HLAs was completed using a ward-agglomerative method. Networks were generated using 40 HLA associated unique genes and hub genes were investigated. HLAs including HLA-DMA, HLA-DMB, HLA-DOA and HLA-DRB6 were associated with delayed recurrence in both discovery (204 HCC cases) and validation (372 HCC cases) cohorts. Clustering analyses revealed 40 genes associated with these four HLAs in both cohorts. A set of seven genes (NCF4, TYROBP, LCP2, ZAP70, PTPRC, FYN and WAS) was found co-expressed at gene-gene interaction level in both cohorts. Furthermore, survival analysis revealed seven HLA-linked genes as predictors of delayed recurrence. Multivariate analysis also predicted that mean expression of 7-gene is an independent predictor of delayed recurrence in both cohorts. We conclude that the expression of 7-gene signature may lead to improved patient prognosis. Further studies are required for consideration in clinical practice.Publication Targeted inhibition of fibroblast growth factor receptor 1-GLI through AZD4547 and GANT61 modulates breast cancer progression(Frontiers Media Sa, 2021-10-13) Riaz, Syeda Kiran; Khan, Walizeb; Wang, Fen; Khaliq, Tanwir; Malik, Amber; Razia, Eisha Tir; Khan, Jahangir Sarwar; Haque, Shafiul; Hashem, Anwar M.; Alkhayyat, Shadi S.; Azhar, Najiah Esam; Harakeh, Steve; Ansari, Mohammad Javed; Haq, Farhan; Malik, Muhammad Faraz Arshad; Haque, Shafiul; Bursa Uludağ Üniversitesi/Tıp Fakültesi; 0000-0002-2989-121X; AAN-2946-2020The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1-GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1-GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.