Browsing by Subject "Colorectal cancer (CRC)"

Now showing 1 - 5 of 5
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    CLIQUES FOR IDENTIFICATION OF GENE SIGNATURES FOR COLORECTAL CANCER ACROSS POPULATION
    (Office of the Vice Chancellor for Research, 2012-04-13) Pradhan, Meeta P.; Nagulapalli, Kshithija; Palakal, Mathew J.
    Introduction: Colorectal cancer (CRC) is one of the most common cancers diagnosed worldwide. Studies have correlated CRC with dietary habits and environmental conditions. We developed a novel network based approach where cliques and their connectivity profiles explained the variation and similarity in CRC across four populations- China, Germany, Saudi Arabia and USA. Methods: Networks generated after data preprocessing were analyzed individually based on topological and biological features. Using greedy algorithm, cliques of various sizes were identified in each network and size 7 cliques were further analyzed based on their clique connectivity profile (CCP). Our algorithm considered the interaction of cliques based on two parameters: (i) Identification of common (links) genes; (ii) CliqueStrength. The cliques were evaluated by two conditions (a) Maximum number of common genes across cliques and highest CliqueStrength and (b) Minimum number of common genes across cliques and highest CliqueStrength. Results: Large numbers of genes are found to be common between USA, China and Germany. Highly scored nodes based on topological parameters are TP53, SRC, ESR1, SMAD3, GRB2, CREBBP, EGFR, SMAD2, and CSN2KA1. Signal transduction, protein phosphorylation etc., were found to be important GO biological processes. Number of unique size 7 cliques identified in all the population is 650. 49 common cliques identified included genes- EGFR, GRB2, PIK3R1, PTPN6, BRCA1, SMAD2, TP53, CSN2 etc. We found 20 cliques that are uniquely identified for USA, 10 for Germany and one for China. Cliques include genes that are both well studied, less-studied in CRC; but are targets in other cancers. Conclusion: With CCP, we were able to identify commonality, uniqueness and divergence among the populations. Furthermore, comparing all cliques (their CCP) as gene-signatures across populations can help to identify efficient drug targets. Results were consistent with other studies and demonstrate the power of cliques to study CRC across populations.
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    GA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer
    (Elsevier, 2022) Komanduri, Srinadh; Dominitz, Jason A.; Rabeneck, Linda; Kahi, Charles; Ladabaum, Uri; Imperiale, Thomas F.; Byrne, Michael F.; Lee, Jeffrey K.; Lieberman, David; Wang, Andrew Y.; Sultan, Shahnaz; Pohl, Heiko; Muthusamy, V. Raman; Medicine, School of Medicine
    In 2018 the American Gastroenterological Association’s (AGA) Center for GI Innovation and Technology (CGIT) convened a consensus conference, entitled, “Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes.” The conference participants, which included more than 60 experts in colorectal cancer (CRC), considered recent improvements in CRC screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.
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    Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment
    (MDPI, 2023-12-21) Alipourgivi, Faranak; Motolani, Aishat; Qiu, Alice Y.; Qiang, Wenan; Yang, Guang-Yu; Chen, Shuibing; Lu, Tao; Pharmacology and Toxicology, School of Medicine
    Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC-the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.
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    The Role and Therapeutic Potential of miRNAs in Colorectal Liver Metastasis
    (Office of the Vice Chancellor for Research, 2015-04-17) Bansal, Ruchi; Sahu, Smiti Snigdha; Nabinger, Sarah C.; Guanglong, Jiang; Bates, Alison; Lee, Sangbin; Hiromi, Tanaka; Liu, Yunlong; Kota, Janaiah
    Colorectal cancer (CRC) is the third most common malignancy worldwide. Liver metastasis occurs in 60% of CRC patients and responds poorly to the available treatments making it the major cause of their mortality. MicroRNAs (miRNAs) are highly conserved, endogenously encoded small, non-coding RNA molecules that regulate global gene expression. The role of microRNAs in cancer pathogenesis, including CRC, has been well documented. However, in-depth miRNA expression analysis on a large cohort of CRC tumors is needed to identify the clinically relevant miRNAs and explore their potential to target liver metastases. To this purpose, we analyzed miRNA expression data of 406 CRC tumors from the publicly available colorectal cancer genome sequencing project and identified 58 miRNAs that were significantly downregulated. 10 miRNAs were selected for further analyses that were either known to target genes in cellular pathways or located within the commonly lost chromosomal loci associated with CRC liver metastases. Of these 10 miRNAs, miR-132, miR-378f, miR-605 and miR-1976 showed significant downregulation with >2 fold change (p>0.05) in primary and CRC liver metastasis tissues and in CRC cell lines. To investigate their anti-tumorigenic and metastatic properties, we transfected 3 different CRC cell lines (SW620, HCT-116 and CT-26) with miR-mimics and subjected them to cell proliferation, apoptosis and cell transformation assays. Ectopic expression of miR-378f, -605 and -1976 suppressed CRC cell proliferation, anchorage independent growth, migration and invasion and induced apoptosis. Interestingly, CRC patients with high miR-378f and miR-1976 had better survival compared to low expressing patients (p<0.044). Our in vitro data suggest the anti-tumorigenic/metastatic properties of miR-378f, -605 and -1976 in CRC. Further understanding of their functions and in vivo therapeutic evaluations may help in developing novel therapeutic strategies for this malignancy.
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    Systems biology approach to obtain significant modules of immune therapy and colorectal cancer
    (Office of the Vice Chancellor for Research, 2016-04-08) Daulatabad, Swapna Vidhur; Pradhan, Meeta; Palakal, Mathew J.
    Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There has been a lot of research around genes influencing CRC, despite its extensive understanding on the genetic perspective and the emergence of drugs targeting these genes, the tumor progression could be hardly mitigated. However, immune therapy has recently been observed to be effective in CRC treatment and diagnosis. This study focuses on developing a statistically validated multi-feature analytical approach to identify immuno-oncology targets. The features considered in this study were gene expression, DNA methylation, concepts from literature and immuno-cancer pathways. The network algorithm will identify the potentially relevant immuno-oncology modules of CRC. For the study level-3 data (7.2 gigabytes) of gene expression and DNA methylation was obtained from The Cancer Genome Atlas. Around 13000 genes were identified to be significant from the gene expression data analysis and 19000 genes significant in DNA methylation data. The CRC and Immuno-oncology concepts were manually annotated from 50 peer reviewed articles. The output of the preliminary analysis could predict 95 concepts annotated to the 1587 significant genes and were integrated into the network. The top rank concepts in terms of genes associated were ‘apoptosis’, ‘transforming growth factor’, ‘protein arginine methyltransferase’, ‘carcinoembryonic antigen’ and ‘methyl binding protein’. The gene annotated with highest number of concepts was ‘PRMT5’, ‘CSF2’, ‘CFLAR’ and ‘MLH1’. These genes were observed in the literature as targets of CRC.