ANALYSIS OF TRANSCRIPTOME DATA FOR THE EVALUATION OF METABOLIC DEREGULATION IN CANCER

Download

thsis_last_version.pdf

Date

2021-6-28

Author

Sheraj, Ilir

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

496
views

269
downloads

The great potential of cancer metabolism in tumor development as well as treatment has been appreciated in recent years. In this study, an extensive list of enzymes relevant to central cellular metabolism and metabolite transporters were manually curated. A pan cancer differential expression of these genes between tumor and their normal counterpart was analyzed in an attempt to better understand tumor bioenergetics, catabolism and anabolism in general. Major deregulation of these genes, particularly the enzymes involved in NADPH metabolism was observed in Liver Hepatocellular Carcinoma (LIHC). LIHC is an extremely aggressive treatment resistant disease with poor prognosis and overall survival (OS), probably due to the ability of the organ to detoxify chemotherapy drugs. AKR1B10 is an NADPH utilizing enzyme whose expression was increased from a very early stage in most LIHC patients and was associated with low OS. However, mechanistic underpinnings of this association are unknown. To address this and the context in which it occurs we hypothesized a potential connection of AKR1B10 with the pentose phosphate pathway (PPP), a glucose metabolizing pathway that generates NADPH. Using various bioinformatics and computational approaches, we found that AKR1B10 works in concert with PPP and a number of other detoxifying enzymes to enhance tumor aggressiveness. In addition, we report the use of latest tools in machine learning to build multi-gene signature prognostic models for highly significant LIHC patient stratification.

Subject Keywords

Tumor Metabolism, LIHC, AKR1B10, TCGA

URI

https://hdl.handle.net/11511/92003

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Modeling and Characterization of Nanomedicine Transport within Tumor Microenvironment across Scales Akalın, Ali Aykut; Özçelikkale, Altuğ (2022-09-19) Despite significant advances in recent decades, diagnosis and treatment of cancer remain to be a major challenge. Advances in nanotechnology have enabled numerous nanoparticle (NP) formulations for efficient delivery of drugs and diagnostic agents to the target tumor site. The size, shape, charge, and surface characteristics of so-called nanomedicine can be tuned to affect the interactions of the NP with the physiological environment [1]. However, design efforts to develop nanomedicine for efficient deliver...
Synthesis and biological evaluation of novel pyrazolic chalcone derivatives as novel hepatocellular carcinoma therapeutics. Hawash, Mohammed M. A.; Kahraman, Deniz Cansen; Eren, Fikriye; Atalay, Rengül; BAYTAŞ, Sultan (2017-03-31) Despite having the second highest mortality associated with cancer, currently Sorafenib is the only FDA-approved chemotherapeutic agent available for liver cancer patients which can only improve survival for few months. In this study, various pyrazolic chalcone analogous compounds were synthesized and evaluated as potential chemotherapeutic agents for the treatment of hepatocellular carcinoma (HCC). Modifying the central pyrazole ring at the C(3)-position with different heteroaryl rings and substituting the...
Nanoparticles Based Drug Delivery Systems to Overcome Multidrug Resistance in Cancer The Role of Membrane Lipids Proteins and Carbohydrates Özlüer, Özlem; Yalçın Azarkan, Serap; Gündüz, Ufuk (null; 2016-09-28) Multidrug resistance (MDR) is a major problem in success of cancer chemotherapy on tumor cell growth, limits the prolonged and effective use of chemotherapy. The use of nanomaterial based drug carriers in cancer treatment offers exciting opportunities to enhance delivery of therapeutics to the tumor site (1). This is also known as targeted drug delivery providing differential distribution of drugs to the tumor site while significantly reducing the overall toxicity. Here, we critically discuss the role of th...
A comparative study on EpCAM antibody immobilization on gold surfaces and microfluidic channels for the detection of circulating tumor cells Cetin, Didem; Okan, Meltem; Bat, Erhan; Külah, Haluk (2020-04-01) Detection of circulating tumor cells (CTCs) from the bloodstream holds great importance to diagnose cancer at early stages. However, CTCs being extremely rare in blood makes them difficult to reach. In this paper, we introduced different surface modification techniques for the enrichment and detection of MCF-7 in microfluidic biosensor applications using gold surface and EpCAM antibody. Mainly, two different mechanisms were employed to immobilize the antibodies; covalent bonding and bioaffinity interaction....
Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer TASKOPARAN, Betul; SEZA, Esin Gulce; Demirkol, Secil; TUNCER, Sinem; Stefek, Milan; Gure, Ali Osmay; Banerjee, Sreeparna (2017-12-01) Aldo-keto reductases (including AKR1B1 and AKR1B10) constitute a family of oxidoreductases that have been implicated in the pathophysiology of diabetes and cancer, including colorectal cancer (CRC). Available data indicate that, despite their similarities in structure and enzymatic functions, their roles in CRC may be divergent. Here, we aimed to determine the expression and functional implications of AKR1B1 and AKR1B10 in CRC.

Citation Formats

I. Sheraj, “ANALYSIS OF TRANSCRIPTOME DATA FOR THE EVALUATION OF METABOLIC DEREGULATION IN CANCER,” Ph.D. - Doctoral Program, Middle East Technical University, 2021.