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https://www.readbyqxmd.com/read/29316255/proteome-heterogeneity-in-colorectal-cancer
#1
REVIEW
Lay Cheng Lim, Yang Mooi Lim
Tumour heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumour subtypes. Recent publications in the past ten years have revealed proteome heterogeneity between different colorectal tumours and within the same tumour site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumour (intratumour heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumour heterogeneity)...
January 5, 2018: Proteomics
https://www.readbyqxmd.com/read/29315503/the-clinical-implications-of-immunogenomics-in-colorectal-cancer-a-path-for-precision-medicine
#2
REVIEW
Jenny M Riley, Ashley W Cross, Chrystal M Paulos, Mark P Rubinstein, John Wrangle, E Ramsay Camp
Colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths in the United States. Large multi-omic databases, such as The Cancer Genome Atlas and the International Colorectal Cancer Subtyping Consortium, have identified distinct molecular subtypes related to anatomy. The identification of genomic alterations in CRC is now critical because of the recent success and US Food and Drug Administration approval of pembrolizumab and nivolumab for microsatellite-instable tumors...
January 9, 2018: Cancer
https://www.readbyqxmd.com/read/29306042/associations-between-molecular-classifications-of-colorectal-cancer-and-patient-survival-a-systematic-review
#3
REVIEW
Elizabeth Alwers, Min Jia, Matthias Kloor, Hendrik Bläker, Hermann Brenner, Michael Hoffmeister
BACKGROUND & AIMS: Colorectal cancer (CRC) is a heterogeneous disease with different mechanisms of pathogenesis. Classification systems have been proposed based on molecular features of tumors, but none are used in clinical practice. We performed a systematic review of studies on the associations between molecular classifications of CRC and patient survival. METHODS: We searched the PubMed, Embase, Cochrane, and Web of Science databases for combinations of terms related to CRC, molecular markers, subtype classifications, and survival (overall survival, disease-specific survival, disease-free survival)...
January 3, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29305587/consensus-molecular-subtypes-of-colorectal-cancer-are-recapitulated-in-in-vitro-and-in-vivo-models
#4
Janneke F Linnekamp, Sander R van Hooff, Pramudita R Prasetyanti, Raju Kandimalla, Joyce Y Buikhuisen, Evelyn Fessler, Prashanthi Ramesh, Kelly A S T Lee, Grehor G W Bochove, Johan H de Jong, Kate Cameron, Ronald van Leersum, Hans M Rodermond, Marek Franitza, Peter Nürnberg, Laura R Mangiapane, Xin Wang, Hans Clevers, Louis Vermeulen, Giorgio Stassi, Jan Paul Medema
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed...
January 5, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29285252/immunological-landscape-of-consensus-clusters-in-colorectal-cancer
#5
Pawel Karpinski, Joanna Rossowska, Maria Malgorzata Sasiadek
Recent, large-scale expression-based subtyping has advanced our understanding of the genomic landscape of colorectal cancer (CRC) and resulted in a consensus molecular classification that enables the categorization of most CRC tumors into one of four consensus molecular subtypes (CMS). Currently, major progress in characterization of immune landscape of tumor-associated microenvironment has been made especially with respect to microsatellite status of CRCs. While these studies profoundly improved the understanding of molecular and immunological profile of CRCs heterogeneity less is known about repertoire of the tumor infiltrating immune cells of each CMS...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285234/targeted-next-generation-sequencing-in-chinese-colorectal-cancer-patients-guided-anti-egfr-treatment-and-facilitated-precision-cancer-medicine
#6
Helei Hou, Dong Liu, Chuantao Zhang, Yanxia Jiang, Guifang Lu, Na Zhou, Xiaonan Yang, Xiaoping Zhang, Zhuokun Li, Hongmei Zhu, Zhaoyang Qian, Xiaochun Zhang
Objective: Colorectal cancer (CRC) patients with both RAS and BRAF wild-type tumors determined by non-next generation sequencing (NGS) testing may still not respond due to the presence of additional mutated genes such as PIK3CA or PTEN. In this study, a broad, hybrid capture-based NGS assay was used to identify RAS, BRAF and additional targetable genetic alterations from Chinese CRC tissues. Methods: Fifty-seven cases of CRC were enrolled, and all the patients signed the informed consent...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259073/phase-ii-study-of-panitumumab-in-ras-wild-type-metastatic-adenocarcinoma-of-small-bowel-or-ampulla-of-vater
#7
Pat Gulhati, Kanwal Raghav, Rachna Shroff, Gauri Varadhachary, Milind Javle, Wei Qiao, Huamin Wang, Jeffrey Morris, Robert Wolff, Michael J Overman
LESSONS LEARNED: Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted...
December 19, 2017: Oncologist
https://www.readbyqxmd.com/read/29242316/colorectal-cancer-consensus-molecular-subtypes-translated-to-preclinical-models-uncover-potentially-targetable-cancer-cell-dependencies
#8
Anita Sveen, Jarle Bruun, Peter W Eide, Ina A Eilertsen, Lorena Ramirez, Astrid Murumägi, Mariliina A Arjama, Stine A Danielsen, Kushtrim Kryeziu, Elena Elez, Josep Tabernero, Justin Guinney, Hector G Palmer, Arild Nesbakken, Olli Kallioniemi, Rodrigo Dienstmann, Ragnhild A Lothe
PURPOSE: Response to standard oncological treatment is limited in colorectal cancer (CRC). The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing, however, drug discovery is currently limited by the lack of translation of CMS to preclinical models. EXPERIMENTAL DESIGN: We analyzed CMS in primary CRCs, cell lines and patient-derived xenografts (PDXs). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell-intrinsic gene expression signals, and performed high-throughput in vitro drug screening (n=459 drugs) to analyze subtype-specific drug sensitivities...
December 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29241727/simple-classifiers-for-molecular-subtypes-of-colorectal-cancer
#9
Woo Gyeong Kim, Joo Yeon Kim, Do Youn Park
BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) is a heterogeneous disease entity with a diverse biological pathogenesis. This study aims to validate the two studies published in 2013 which established a separate CRC molecular subtype classification by utilizing a rapidly accessible miniclassifier, and verify a simplified version thereof. PATIENTS AND METHODS: Participants diagnosed with CRC (n = 568) were subtyped in three classifications for characteristic, and prognostic purposes...
December 11, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/29228716/sox2-modulates-motility-and-enhances-progression-of-colorectal-cancer-via-the-rho-rock-signaling-pathway
#10
Junheng Zheng, Lixiao Xu, Yubin Pan, Shuyi Yu, Hongbo Wang, Derek Kennedy, Yan Zhang
Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212164/targeted-sequencing-of-established-and-candidate-colorectal-cancer-genes-in-the-colon-cancer-family-registry-cohort
#11
Leon Raskin, Yan Guo, Liping Du, Mark Clendenning, Christophe Rosty, Noralane M Lindor, Stephen B Gruber, Daniel D Buchanan
The underlying genetic cause of colorectal cancer (CRC) can be identified for 5-10% of all cases, while at least 20% of CRC cases are thought to be due to inherited genetic factors. Screening for highly penetrant mutations in genes associated with Mendelian cancer syndromes using next-generation sequencing (NGS) can be prohibitively expensive for studies requiring large samples sizes. The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA pooling NGS strategy...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29192179/cmscaller-an-r-package-for-consensus-molecular-subtyping-of-colorectal-cancer-pre-clinical-models
#12
Peter W Eide, Jarle Bruun, Ragnhild A Lothe, Anita Sveen
Colorectal cancers (CRCs) can be divided into four gene expression-based biologically distinct consensus molecular subtypes (CMS). This classification provides a potential framework for stratified treatment, but to identify novel CMS-drug associations, translation of the subtypes to pre-clinical models is essential. The currently available classifier is dependent on gene expression signals from the immune and stromal compartments of tumors and fails to identify the poor-prognostic CMS4-mesenchymal group in immortalized cell lines, patient-derived organoids and xenografts...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29187560/multi-omics-approach-reveals-distinct-differences-in-left-and-right-sided-colon-cancer
#13
Wangxiong Hu, Yanmei Yang, Xiaofen Li, Minran Huang, Fei Xu, Weiting Ge, Suzhan Zhang, Shu Zheng
Increasing evidence suggests that left-sided colon cancer (LCC) and right-sided colon cancer (RCC) are emerging as two different colorectal cancer (CRC) types with distinct clinical characteristics. However, the discrepancy in the underlying molecular event between these types of cancer has not been thoroughly elucidated to date and warrants comprehensive investigation. To this end, an integrated data set from The Cancer Genome Atlas (TCGA) was used to compare and contrast LCC and RCC, covering mutation, DNA methylation, gene expression, and miRNA...
November 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29183322/extracts-of-zuo-jin-wan-a-traditional-chinese-medicine-phenocopies-5-htr1d-antagonist-in-attenuating-wnt-%C3%AE-catenin-signaling-in-colorectal-cancer-cells
#14
Jielu Pan, Yangxian Xu, Haiyan Song, Xiqiu Zhou, Zemin Yao, Guang Ji
BACKGROUND: In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW remains unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues. The present study aimed at investigating effect of ZJW extracts on the biological function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/β-catenin signaling pathway...
November 28, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29180604/classifying-colorectal-cancer-by-tumor-location-rather-than-sidedness-highlights-a-continuum-in-mutation-profiles-and-consensus-molecular-subtypes
#15
Jonathan M Loree, Allan Al Pereira, Michael Lam, Alexandra N Willauer, Kanwal Raghav, Arvind Dasari, Van K Morris, Shailesh M Advani, David G Menter, Cathy Eng, Kenna Shaw, Russell Broaddus, Mark J Routbort, Yusha Liu, Jeffrey Morris, Rajyalakshmi Luthra, Funda Meric-Bernstam, Michael J Overman, Dipen M Maru, Scott Kopetz
PURPOSE: Colorectal cancers (CRCs) are classified as right/left sided based on whether they occur before/after the splenic flexure, with established differences in molecular subtypes and outcomes.  However, it is unclear if this division is optimal and whether precise tumor location provides further information. EXPERIMENTAL DESIGN: In 1,876 patients with CRC we compared mutation prevalence and overall survival (OS) according to side and location. Consensus Molecular Subtype (CMS) was compared in a separate cohort of 608 patients...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#16
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#17
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29137421/gper-mediates-differential-effects-of-estrogen-on-colon-cancer-cell-proliferation-and-migration-under-normoxic-and-hypoxic-conditions
#18
Viviana Bustos, Áine M Nolan, Anke Nijhuis, Harry Harvey, Alexandra Parker, Richard Poulsom, Jean McBryan, Warren Thomas, Andrew Silver, Brian J Harvey
The estrogen receptor ERβ is the predominant ER subtype expressed in normal well-differentiated colonic epithelium. However, ERβ expression is lost under the hypoxic microenvironment as colorectal cancer (CRC) malignancy progresses. This raises questions about the role of signalling through other estrogen receptors such as ERα or G-protein coupled estrogen receptor (GPER, GPR30) by the estrogen 17β-estradiol (E2) under hypoxic conditions after ERβ is lost in CRC progression. We tested the hypothesis that E2 or hypoxia can act via GPER to contribute to the altered phenotype of CRC cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130628/characterization-of-genetic-intratumor-heterogeneity-in-colorectal-cancer-and-matching-patient-derived-spheroid-cultures
#19
Sigrid S Árnadóttir, Maria Jeppesen, Philippe Lamy, Jesper B Bramsen, Iver Nordentoft, Michael Knudsen, Søren Vang, Mogens R Madsen, Ole Thastrup, Jacob Thastrup, Claus L Andersen
Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, while the other half was used for DNA and RNA purification...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29118272/beyond-cancer-genes-colorectal-cancer-as-robust-intrinsic-states-formed-by-molecular-interactions
#20
Ruoshi Yuan, Suzhan Zhang, Jiekai Yu, Yanqin Huang, Demin Lu, Runtan Cheng, Sui Huang, Ping Ao, Shu Zheng, Leroy Hood, Xiaomei Zhu
Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular-cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures...
November 2017: Open Biology
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