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    A Differential Transcriptional Regulome Approach to Unpack Cancer Biology: Insights on Renal Cell Carcinoma Subtypes
    (Mary Ann Liebert, Inc, 2023) Caliskan, Aysegul; Arga, Kazim Yalcin
    Cancer research calls for new approaches that account for the regulatory complexities of biology. We present, in this study, the differential transcriptional regulome (DIFFREG) approach for the identification and prioritization of key transcriptional regulators and apply it to the case of renal cell carcinoma (RCC) biology. Of note, RCC has a poor prognosis and the biomarker and drug discovery studies to date have tended to focus on gene expression independent from mutations and/or post-translational modifications. DIFFREG focuses on the differential regulation between transcription factors (TFs) and their target genes rather than differential gene expression and integrates transcriptome profiling with the human transcriptional regulatory network to analyze differential gene regulation between healthy and RCC cases. In this study, RNA-seq tissue samples (n = 1020) from the Cancer Genome Atlas (TCGA), including healthy and tumor subjects, were integrated with a comprehensive human TF-gene interactome dataset (1122603 interactions between 1289 TFs and 25177 genes). Comparative analysis of DIFFREG profiles, consisting of perturbed TF-gene interactions, from three common subtypes (clear cell RCC, papillary RCC and chromophobe RCC) revealed subtype-specific alterations, supporting the hypothesis that these signatures in the transcriptional regulome profiles may be considered potential biomarkers that may play an important role in elucidating the molecular mechanisms of RCC development and translating knowledge about the genetic basis of RCC into the clinic. In addition, these indicators may help oncologists make the best decisions for diagnosis and prognosis management.
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    The repertoire of glycan alterations and glycoproteins in human cancers
    (2021) Kori, Medi; Aydın, Büşra; Gülfidan, Gizem; Beklen, Hande; Kelesoglu, Nurdan; Çalışkan İşcan, Ayşegül; Turanli, Beste; Erzik, Can; Karademir, Betul; Arga, Kazim Yalcin
    Cancer as the leading cause of death worldwide has many issues that still need to be addressed. Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans. In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations. Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy. Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations. Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers. While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.