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Colorectal tumour marker

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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/27893714/the-lim-protein-ajuba-promotes-colorectal-cancer-cell-survival-through-suppression-of-jak1-stat1-ifit2-network
#2
H Jia, L Song, Q Cong, J Wang, H Xu, Y Chu, Q Li, Y Zhang, X Zou, C Zhang, Y E Chin, X Zhang, Z Li, K Zhu, B Wang, H Peng, Z Hou
The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27884016/expression-profiling-of-budding-cells-in-colorectal-cancer-reveals-an-emt-like-phenotype-and-molecular-subtype-switching
#3
Linde De Smedt, Sofie Palmans, Daan Andel, Olivier Govaere, Bram Boeckx, Dominiek Smeets, Eva Galle, Jasper Wouters, David Barras, Madeleine Suffiotti, Jeroen Dekervel, Thomas Tousseyn, Gert De Hertogh, Hans Prenen, Sabine Tejpar, Diether Lambrechts, Xavier Sagaert
BACKGROUND: Tumour budding, described as the presence of single cells or small clusters of up to five tumour cells at the invasive margin, is established as a prognostic marker in colorectal carcinoma. In the present study, we aimed to investigate the molecular signature of tumour budding cells and the corresponding tumour bulk. METHODS: Tumour bulk and budding areas were microdissected and processed for RNA-sequencing. As little RNA was obtained from budding cells, a special low-input mRNA library preparation protocol was used...
November 24, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27880730/loss-of-zg16-is-regulated-by-mir-196a-and-contributes-to-stemness-and-progression-of-colorectal-cancer
#4
Xiaobing Chen, Peng Du, Junjun She, Liang Cao, Yingchao Li, Hongping Xia
Colorectal cancer (CRC) is one of the most common malignant tumour and the leading cause of cancer-related mortality worldwide. Clarification of the mechanism that underlies CRC tumorigenesis and progression therefore is urgently needed ffor developing novel therapies. Through analysis of The Cancer Genome Atlas (TCGA) dataset, we identified an interesting gene, ZG16, which is significantly decreased in CRC samples compared to adjacent non-tumor tissues and associated with prognosis of patients. We found that the expression of ZG16 correlated with CRC related genes which were regulated by APC/CTNNB1 pathway...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822332/extracellular-matrix-gene-expression-profiling-using-microfluidics-for-colorectal-carcinoma-stratification
#5
Christopher J Hayes, Catriona M Dowling, Susan Dwane, Mary E McCumiskey, Shona M Tormey, B Anne Merrigan, John C Coffey, Patrick A Kiely, Tara M Dalton
In cancer, biomarkers have many potential applications including generation of a differential diagnosis, prediction of response to treatment, and monitoring disease progression. Many molecular biomarkers have been put forward for different diseases but most of them do not possess the required specificity and sensitivity. A biomarker with a high sensitivity has a low specificity and vice versa. The inaccuracy of the biomarkers currently in use has led to a compelling need to identify more accurate markers with diagnostic and prognostic significance...
September 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27797228/evaluation-of-mt1xt20-single-quasi-monomorphic-mononucleotide-marker-for-characterizing-microsatellite-instability-in-persian-lynch-syndrome-patients
#6
Najmeh Farahani, Parvaneh Nikpou, Mohammad Hassan Emami, Morteza Hashemzadeh, Mehrdad Zeinalian, Seyed Shervin Shariatpanahi, Rasoul Salehi
BACKGROUND: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27766737/micrometastasis-in-colorectal-cancer-does-it-affect-staging
#7
Gholamreza Mohajeri, Kavak Hejab, Saba Sheikhbahaei, Mohammadreza Mohajeri, Negar Niknam, Alireza Mohammadi
BACKGROUND: Micrometastasis (MM) in colorectal cancer (CRC) is not considered in tumour-node-metastasis (TNM) staging currently and also the prognostic significance of these occult tumoural cells is not proven yet. This study was designed to find whether MM to bone marrow (BM) and/or liver cause upstaging of the tumour according to conventional staging system and if it may alter the survival rate. METHODS: Thirty-eight CRC patients who were candidates of surgical procedure were enrolled in our cross-sectional study...
October 21, 2016: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/27750112/the-role-of-s100a4-mts1-in-apc-and-smad4-driven-tumour-onset-and-progression
#8
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27729429/mtor-activity-and-its-prognostic-significance-in-human-colorectal-carcinoma-depending-on-c1-and-c2-complex-related-protein-expression
#9
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27672217/the-role-of-mirna-21-and-epithelial-mesenchymal-transition-emt-process-in-colorectal-cancer
#10
Anelisa Jaca, Padmini Govender, Michael Locketz, Richard Naidoo
AIMS: The study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer. METHODS: H&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed...
September 26, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27621566/pancreatic-cancer-are-liquid-biopsies-ready-for-prime-time
#11
REVIEW
Alexandra R Lewis, Juan W Valle, Mairead G McNamara
Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms...
August 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27576678/mirna-profiling-of-circulating-epcam-extracellular-vesicles-promising-biomarkers-of-colorectal-cancer
#12
Marie Stampe Ostenfeld, Steffen Grann Jensen, Dennis Kjølhede Jeppesen, Lise-Lotte Christensen, Stine Buch Thorsen, Jan Stenvang, Michael Lykke Hvam, Anni Thomsen, Peter Mouritzen, Mads Heilskov Rasmussen, Hans Jørgen Nielsen, Torben Falck Ørntoft, Claus Lindbjerg Andersen
Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. These contain biomolecules, including proteins and microRNAs (miRNAs). Both circulating EVs and miRNAs have received much attention as biomarker candidates for non-invasive diagnostics. Here we describe a sensitive analytical method for isolation and subsequent miRNA profiling of epithelial-derived EVs from blood samples of patients with colorectal cancer (CRC). The epithelial-derived EVs were isolated by immunoaffinity-capture using the epithelial cell adhesion molecule (EpCAM) as marker...
2016: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/27542763/-positron-emission-tomography-pet-in-gastro-intestinal-cancer
#13
Myriam Wartski
The existing recommendations for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) use in digestive cancers (excluding neuroendocrine tumours) are summarized in the present article. FDG-PET/CT is nowadays a routine imaging modality for digestive malignancies and its use is currently increasing. FDG-PET/CT is considered to be a crucial tool in pretherapeutic assessment of esophageal, localized pancreatic and anal cancer. It represents a key exam in suspicion of recurrence of colorectal cancer in case of elevated serum tumor markers...
September 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27514543/the-interaction-of-wnt-11-and-signalling-cascades-in-prostate-cancer
#14
Sarah Koushyar, Guy H Grant, Pinar Uysal-Onganer
Prostate cancer (PCa) is the second most common cancer among the male population. Conventional therapies target androgen signalling, which drives tumour growth; however, they provide limited survival benefits for patients. It is essential, therefore, to develop a more specific biomarker than the current gold standard, PSA testing. The Wnt signalling pathway induces expression of target genes through cell surface receptors. A non-canonical member of this family, Wnt-11, is evolutionarily highly conserved and is normally expressed by various cells in the developing embryo, as well as in the heart, liver and skeletal muscle of adult humans...
August 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27513864/intricate-macrophage-colorectal-cancer-cell-communication-in-response-to-radiation
#15
Ana T Pinto, Marta L Pinto, Sérgia Velho, Marta T Pinto, Ana P Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Raquel Seruca, Mário A Barbosa, Marc Mareel, Maria J Oliveira, Sónia Rocha
Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27499912/the-infiltration-and-prognostic-importance-of-th1-lymphocytes-vary-in-molecular-subgroups-of-colorectal-cancer
#16
Agnes Ling, Ida V Lundberg, Vincy Eklöf, Maria L Wikberg, Åke Öberg, Sofia Edin, Richard Palmqvist
Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status)...
January 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27479846/modified-two-dimensional-response-as-surrogate-marker-of-overall-survival-in-patients-with-metastatic-colorectal-cancer
#17
Goro Nakayama, Tsutomu Fujii, Kenta Murotani, Keisuke Uehara, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yuichi Ando, Yasuhiro Kodera
The identification of surrogate markers for long-term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two-dimensional response (2-DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study population consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin-based chemotherapy plus bevacizumab. 2-DR was defined as an area enclosed by coordinate points, including early tumour shrinkage (ETS) at 8 weeks, depth of response (DpR) at nadir and 20% increase over nadir at progression...
August 1, 2016: Cancer Science
https://www.readbyqxmd.com/read/27465491/role-of-sumo-activating-enzyme-in-cancer-stem-cell-maintenance-and-self-renewal
#18
Li Du, Yi-Jia Li, Marwan Fakih, Rebecca L Wiatrek, Marjun Duldulao, Zhenbin Chen, Peiguo Chu, Julio Garcia-Aguilar, Yuan Chen
Cancer stem cells (CSCs) have key roles in treatment resistance, tumour metastasis and relapse. Using colorectal cancer (CC) cell lines, patient-derived xenograft (PDX) tissues and patient tissues, here we report that CC CSCs, which resist chemoradiation, have higher SUMO activating enzyme (E1) and global SUMOylation levels than non-CSCs. Knockdown of SUMO E1 or SUMO conjugating enzyme (E2) inhibits CC CSC maintenance and self-renewal, while overexpression of SUMO E1 or E2 increases CC cell stemness. We found that SUMOylation regulates CSCs through Oct-1, a transcription factor for aldehyde dehydrogenases (ALDHs)...
2016: Nature Communications
https://www.readbyqxmd.com/read/27465284/excessive-collagen-turnover-products-are-released-during-colorectal-cancer-progression-and-elevated-in-serum-from-metastatic-colorectal-cancer-patients
#19
S N Kehlet, R Sanz-Pamplona, S Brix, D J Leeming, M A Karsdal, V Moreno
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27459899/practical-and-robust-identification-of-molecular-subtypes-in-colorectal-cancer-by-immunohistochemistry
#20
Anne Trinh, Kari Trumpi, Felipe de Sousa E Melo, Xin Wang, Joan H de Jong, Evelyn Fessler, Peter J K Kuppen, Marlies S Reimers, Marloes Swets, Miriam Koopman, Iris D Nagtegaal, Marnix Jansen, Gerrit K J Hooijer, G Johan Offerhaus, Onno Kranenburg, Cornelis J A Punt, Jan Paul Medema, Florian Markowetz, Louis Vermeulen
PURPOSE: Recent transcriptomic analyses have identified four distinct molecular subtypes of colorectal cancer (CRC) with evident clinical relevance. However, the requirement for sufficient quantities of bulk tumor and difficulties in obtaining high quality genome-wide transcriptome data from formalin-fixed paraffin-embedded tissue are obstacles towards widespread adoption of this taxonomy. Here, we develop an immunohistochemistry-based classifier to validate the prognostic and predictive value of molecular CRC subtyping in a multi-center study...
July 26, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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