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https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#1
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27917920/transcriptome-and-long-noncoding-rna-sequencing-of-three-extracellular-vesicle-subtypes-released-from-the-human-colon-cancer-lim1863-cell-line
#2
Maoshan Chen, Rong Xu, Hong Ji, David W Greening, Alin Rai, Keiichi Izumikawa, Hideaki Ishikawa, Nobuhiro Takahashi, Richard J Simpson
Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917697/current-and-future-biomarkers-in-the-treatment-of-colorectal-cancer
#3
Pieter-Jan Cuyle, Hans Prenen
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. CRC develops as a consequence of genomic instability, characterized by various genetic and epigenetic alterations. Its molecular heterogeneity explains the large variability in patient prognosis and treatment response, emphasizing the need for development of accurate prognostic and predictive biomarkers. This article delineates the different pathways of colorectal carcinogenesis and its molecular subtype classification. With this review, we aim to provide a comprehensive overview of the current and future biomarkers guiding clinical decision-making and CRC treatment...
December 5, 2016: Acta Clinica Belgica
https://www.readbyqxmd.com/read/27916938/comprehensive-analysis-of-mirnome-alterations-in-response-to-sorafenib-treatment-in-colorectal-cancer-cells
#4
Anna-Maria Pehserl, Anna Lena Ress, Stefanie Stanzer, Margit Resel, Michael Karbiener, Elke Stadelmeyer, Verena Stiegelbauer, Armin Gerger, Christian Mayr, Marcel Scheideler, Georg C Hutterer, Thomas Bauernhofer, Tobias Kiesslich, Martin Pichler
MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916893/the-interaction-between-dietary-fiber-and-fat-and-risk-of-colorectal-cancer-in-the-women-s-health-initiative
#5
Sandi L Navarro, Marian L Neuhouser, Ting-Yuan David Cheng, Lesley F Tinker, James M Shikany, Linda Snetselaar, Jessica A Martinez, Ikuko Kato, Shirley A A Beresford, Robert S Chapkin, Johanna W Lampe
Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women's Health Initiative prospective cohort (n = 134,017). During a mean 11.7 years (1993-2010), 1952 incident CRC cases were identified...
November 30, 2016: Nutrients
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#6
Paloma Cejas, Alessia Cavazza, Chandri Yandava, Víctor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27880934/tumors-with-unmethylated-mlh1-and-the-cpg-island-methylator-phenotype-are-associated-with-a-poor-prognosis-in-stage-ii-colorectal-cancer-patients
#7
Tao Fu, Yanliang Liu, Kai Li, Weiwei Wan, Emmanouil P Pappou, Christine A Iacobuzio-Donahue, Zachary Kerner, Stephen B Baylin, Christopher L Wolfgang, Nita Ahuja
We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848087/the-initial-symptom-and-motor-progression-in-spinocerebellar-ataxias
#8
Lan Luo, Jie Wang, Raymond Y Lo, Karla P Figueroa, Stefan M Pulst, Pei-Hsin Kuo, Susan Perlman, George Wilmot, Christopher M Gomez, Jeremy D Schmahmann, Henry Paulson, Vikram G Shakkottai, Sarah H Ying, Theresa Zesiewicz, Khalaf Bushara, Michael Geschwind, Guangbin Xia, S H Subramony, Tetsuo Ashizawa, Sheng-Han Kuo
The aim of this study is to determine whether the initial symptom associates with motor progression in spinocerebellar ataxias (SCAs). SCAs are clinically heterogeneous and the initial presentation may represent different subtypes of SCA with different motor progression. We studied 317 participants with SCAs1, 2, 3, and 6 from the Clinical Research Consortium for SCAs (CRC-SCA) and repeatedly measured the severity of ataxia for 2 years. SCA patients were divided into gait-onset and non-gait-onset (speech, vision, and hand dexterity) groups based on the initial presentation...
November 15, 2016: Cerebellum
https://www.readbyqxmd.com/read/27846243/bacterially-associated-transcriptional-remodelling-in-a-distinct-genomic-subtype-of-colorectal-cancer-provides-a-plausible-molecular-basis-for-disease-development
#9
Katie S Lennard, Ryan W Goosen, Jonathan M Blackburn
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC...
2016: PloS One
https://www.readbyqxmd.com/read/27836787/tumor-budding-at-the-invasive-front-of-colorectal-cancer-may-not-be-associated-with-the-epithelial-mesenchymal-transition
#10
Noriyuki Yamada, Tamotsu Sugai, Makoto Eizuka, Koudai Tsuchida, Ryo Sugimoto, Yoshiharu Mue, Masamichi Suzuki, Mitsumasa Osakabe, Noriyuki Uesugi, Kazuyuki Ishida, Kouki Otsuka, Takayuki Matsumoto
Tumor budding is thought to reflect the epithelial-mesenchymal transition (EMT). However, the molecular mechanism linking tumor buds and the EMT remains unclear. Here, we examined the induction of tumor budding and EMT and their association with EMT-related proteins (ZEB1, TWIST, SNAIL and SLUG) in colorectal cancer (CRC). Immunohistochemical expression of pan-cytokeratin was examined for identification of tumor budding in 101 CRCs. Grading of tumor budding was classified into low and high grade groups. Tissue micro-array was conducted to identify tumor budding sites...
November 8, 2016: Human Pathology
https://www.readbyqxmd.com/read/27835898/prognostic-significance-of-usp33-in-advanced-colorectal-cancer-patients-new-insights-into-%C3%AE-arrestin-dependent-erk-signaling
#11
Hongda Liu, Qun Zhang, Kangshuai Li, Zheng Gong, Zhaochen Liu, Yunfei Xu, Mary Hannah Swaney, Kunhong Xiao, Yuxin Chen
Patients with liver metastases of colorectal cancer (CRCLM) have a poorer prognosis compared to colorectal cancer (CRC) patients in local stage. Evaluating the recurrence and overall survival of advanced patients is critical in improving disease treatment and clinical outcome. Here we investigated the expression pattern of USP33, a deubiquitinating enzyme, in both primary CRC tissues and liver metastases tissues. Univariate and multivariate analyses identified that low expression of USP33 in CRCLM tissues indicated high recurrence risk and poor overall prognosis...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27819306/decreased-preoperative-serum-25-hydroxyvitamin-d-levels-in-colorectal-cancer-are-associated-with-systemic-inflammation-and-serrated-morphology
#12
Juha P Väyrynen, Shivaprakash J Mutt, Karl-Heinz Herzig, Sara A Väyrynen, Tiina Kantola, Toni Karhu, Tuomo J Karttunen, Kai Klintrup, Jyrki Mäkelä, Markus J Mäkinen, Anne Tuomisto
Deficiency of vitamin D is associated with increased risk of several types of cancer including colorectal cancer (CRC). However, factors contributing to low levels of 25-hydroxyvitamin D [25(OH)D] in CRC are not clear. Therefore, in this study serum 25(OH)D levels in 117 CRC patients and 86 controls were analyzed and correlated with the clinicopathological data including morphological subtype (serrated or conventional), quantity of tumor infiltrating immune cells, levels of systemic inflammatory markers, and disease outcome...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27783989/mfhas1-promotes-colorectal-cancer-progress-by-regulating-polarization-of-tumor-associated-macrophages-via-stat6-signaling-pathway
#13
Wankun Chen, Yajun Xu, Jing Zhong, Huihui Wang, Meilin Weng, Qian Cheng, Qichao Wu, Zhirong Sun, Hui Jiang, Minmin Zhu, Yu Ren, Pingbo Xu, Jiawei Chen, Changhong Miao
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage...
October 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27729552/impaired-coordination-between-signaling-pathways-is-revealed-in-human-colorectal-cancer-using-single-cell-mass-cytometry-of-archival-tissue-blocks
#14
Alan J Simmons, Cherié R Scurrah, Eliot T McKinley, Charles A Herring, Jonathan M Irish, M Kay Washington, Robert J Coffey, Ken S Lau
Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples...
October 11, 2016: Science Signaling
https://www.readbyqxmd.com/read/27663504/bcl-2-system-analysis-identifies-high-risk-colorectal-cancer-patients
#15
Andreas U Lindner, Manuela Salvucci, Clare Morgan, Naser Monsefi, Alexa J Resler, Mattia Cremona, Sarah Curry, Sinead Toomey, Robert O'Byrne, Orna Bacon, Michael Stühler, Lorna Flanagan, Richard Wilson, Patrick G Johnston, Manuel Salto-Tellez, Sophie Camilleri-Broët, Deborah A McNamara, Elaine W Kay, Bryan T Hennessy, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Jochen H M Prehn
OBJECTIVE: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). DESIGN: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC...
September 23, 2016: Gut
https://www.readbyqxmd.com/read/27661107/rnf43-and-znrf3-are-commonly-altered-in-serrated-pathway-colorectal-tumorigenesis
#16
Catherine E Bond, Diane M McKeone, Murugan Kalimutho, Mark L Bettington, Sally-Ann Pearson, Troy D Dumenil, Leesa F Wockner, Matthew Burge, Barbara A Leggett, Vicki L J Whitehall
Serrated pathway colorectal cancers (CRCs) are characterised by a BRAF mutation and half display microsatellite instability (MSI). The Wnt pathway is commonly upregulated in conventional CRC through APC mutation. By contrast, serrated cancers do not mutate APC. We investigated mutation of the ubiquitin ligases RNF43 and ZNRF3 as alternate mechanism of altering the Wnt signal in serrated colorectal neoplasia. RNF43 was mutated in 47/54(87%) BRAF mutant/MSI and 8/33(24%) BRAF mutant/microsatellite stable cancers compared to only 3/79(4%) BRAF wildtype cancers (p<0...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27636879/germline-mirna-dna-variants-and-the-risk-of-colorectal-cancer-by-subtype
#17
Noralane M Lindor, Melissa C Larson, Melissa S DeRycke, Shannon K McDonnell, Saurabh Baheti, Zachary C Fogarty, Aung Ko Win, John D Potter, Daniel D Buchanan, Mark Clendenning, Polly A Newcomb, Graham Casey, Steven Gallinger, Loïc Le Marchand, John L Hopper, Mark A Jenkins, Ellen L Goode, Stephen N Thibodeau
MicroRNAs (miRNAs) regulate up to one-third of all protein-coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC). In this study, we evaluated germline genetic variation in 1,123 miRNAs in 899 individuals with CRCs categorized by clinical subtypes and in 204 controls...
September 16, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27632639/plasma-mir-122-and-mir-200-family-are-prognostic-markers-in-colorectal-cancer
#18
Melanie Maierthaler, Axel Benner, Michael Hoffmeister, Harald Surowy, Lina Jansen, Phillip Knebel, Jenny Chang-Claude, Hermann Brenner, Barbara Burwinkel
Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards...
January 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27630335/synchronous-type-1-papillary-renal-cell-carcinoma-in-a-patient-with-rectal-adenocarcinoma
#19
Jinhua Piao, Paul Friedman, Sameer Siddiqui, Jula Veerapong, Jin-Ping Lai
Synchronous colorectal cancer (CRC) and renal cell carcinoma (RCC) is relatively rare, particularly when the synchronous RCC is of papillary subtype, which is exceedingly rare. We report a case of a 63-year-old Caucasian man with synchronous CRC and type 1 papillary RCC. After the patient presented with three episodes of melena, colonoscopy followed by biopsy confirmed rectal adenocarcinoma. The computed tomographic imaging also showed an incidental mass of the upper pole of the left kidney suspicious for RCC...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27589478/high-expression-of-the-notch-ligand-jagged-1-is-associated-with-poor-prognosis-after-surgery-for-colorectal-cancer
#20
Masakazu Sugiyama, Eiji Oki, Yu Nakaji, Satoshi Tsutsumi, Naomi Ono, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ohgaki, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara
: The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS), and relapse-free survival (RFS) were evaluated...
September 2, 2016: Cancer Science
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