PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’?

Journal article


Patel, A, Fang, Y, Moore, J, Williams, N, Tripathi, G and Arasaradnam, R 2015. PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’? Gut. https://doi.org/10.1136/gutjnl-2015-309861.700
AuthorsPatel, A, Fang, Y, Moore, J, Williams, N, Tripathi, G and Arasaradnam, R
Abstract

Field cancerisation refers to the process whereby cells acquire pro-tumourigenic mutations that predispose to malignant transformation but do not produce morphological change.1Previous colorectal cancer studies have assumed that the macroscopically normal mucosa (MNM) adjacent to a cancer is biologically unaltered. The aim of this study was to determine if the genetic expression profile of the MNM around a cancer or adenoma is different to that found in healthy controls. 15 patients undergoing colonoscopy were recruited over 12 months; 5 healthy controls, 5 with colorectal adenomas and 5 with adenocarcinoma. Two mucosal pinch biopsies were taken in the rectum, right colon and adjacent to polyp or cancer. mRNA was extracted and gene expression was assessed using standard whole genome micro-array analysis. Differentially expressed genes were identified using three methods of analysis: LIMMA (fold change ratio >1.5 and p value <0.05), Robust Regression (RR) (adjusted p value <0.05) and genes that ‘overlap’ when LIMMA (p value <0.001) and RR (adjusted p value <0.1) are used. Functional analysis was performed using DAVID2software to identify important biological processes that were dysregulated. A large number of genes were dysregulated in the MNM adjacent to cancer or adenoma compared with controls (Table 1). Interestingly, the greatest differences were seen between MNM adjacent to cancer and polyp in chromatin organisation, nucleosome processing, nuclear transport and histone assembly. The most significantly upregulated genes consisted of FUT2, CTSA, MUC2 and SDS and downregulated genes consisted of GREM1, SFRP, HIST1H, IL17B and TFF1.

Year2015
JournalGut
PublisherBMJ
ISSN175749
14683288
Digital Object Identifier (DOI)https://doi.org/10.1136/gutjnl-2015-309861.700
Web address (URL)http://hdl.handle.net/10545/624117
hdl:10545/624117
Publication dates22 Jun 2015
Publication process dates
Deposited09 Aug 2019, 08:51
ContributorsUniversity of Westminster
Permalink -

https://repository.derby.ac.uk/item/9350y/pwe-254-is-the-macroscopically-normal-mucosa-mnm-around-colorectal-cancer-really-normal

  • 8
    total views
  • 0
    total downloads
  • 1
    views this month
  • 0
    downloads this month

Export as

Related outputs

PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have?
Patel, A, Williams, N, Nwokolo, C, Tripathi, G and Arasaradnam, R 2014. PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have? Gut. https://doi.org/10.1136/gutjnl-2014-307263.261
Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids
Jackisch, L, Kumsaiyai, W, Moore, J.D, Al-Daghri, N, Kyrou, I, Barber, T.M, Randeva, H, Kumar, S, Tripathi, G and McTernan, P.G 2018. Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids. Diabetologia. https://doi.org/10.1007/s00125-018-4558-6
Unfolded protein response in adipose tissue of obese diabetic women significantly improved 6 months post bariatric surgery, irrespective of malabsorptive or bypass operation type and correlates with plasma glucose concentration
Voyias, P, Antonysunil, A, Kumasaiyai, W, Kyrou, I, Vrbikova, J, Hainer, V, Fried, M, Sramkova, P, Saravanan, P, Kumar, S, McTernan, P and Tripathi, G 2014. Unfolded protein response in adipose tissue of obese diabetic women significantly improved 6 months post bariatric surgery, irrespective of malabsorptive or bypass operation type and correlates with plasma glucose concentration. bioscientifica. https://doi.org/10.1530/endoabs.34.P269
A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention
Al-Disi, D, Al-Daghri, N, Khan, N, Alsaif, M, Alfadda, A, Sabico, S, Tripathi, G and McTernan, P 2014. A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention. bioscientifica. https://doi.org/10.1530/endoabs.34.P223
Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro
Pushpakom, S.P, Adaikalakoteswari, A, Owen, A, Back, D.J, Tripathi, G, Kumar, S, McTernan, P and Pirmohamed, M 2018. Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes and Vascular Disease Research. https://doi.org/10.1177/1479164118757924
Vitamin D receptor gene polymorphisms modify cardiometabolic response to vitamin D supplementation in T2DM patients
Al-Daghri, N.M, Mohammed, A.K, Al-Attas, O.S, Ansari, M.G.A, Wani, K, Hussain, S.D, Sabico, S, Tripathi, G and Alokail, M.S 2017. Vitamin D receptor gene polymorphisms modify cardiometabolic response to vitamin D supplementation in T2DM patients. Scientific Reports. https://doi.org/10.1038/s41598-017-08621-7
Recepteur d'Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer
Krishnaswamy, S, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2015. Recepteur d'Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer. International Journal of Clinical and Experimental Medicine.
Elevated cord leptin from low B12 mothers predicts birth weight
Antonysunil, A, Vatish, M, Lawson, A, Wood, C, Sivakumar, K, Webster, C, Anderson, N, McTernan, P, Tripathi, G and Saravanan, P 2014. Elevated cord leptin from low B12 mothers predicts birth weight. bioscientifica. https://doi.org/10.1530/endoabs.34.P262
Meal size and frequency influences metabolic endotoxaemia and inflammatory risk but has no effect on diet induced thermogenesis in either lean or obese subjects
Piya, M, Reddy, N, Campbell, A, Hattersley, J, Halder, L, Tripathi, G, Tahrani, A, Kumar, S, Barber, T and McTernan, P 2014. Meal size and frequency influences metabolic endotoxaemia and inflammatory risk but has no effect on diet induced thermogenesis in either lean or obese subjects. bioscientifica. https://doi.org/10.1530/endoabs.34.P226
Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing
Krishnaswamy, S, Mohammed, A.K, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2017. Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing. BMC Cancer. https://doi.org/10.1186/s12885-017-3747-x
Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines
Krishnaswamy, S, Bukhari, I, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2018. Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines. Gene. https://doi.org/10.1016/j.gene.2018.09.027
Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2
Al‐Daghri, N.M, Alokail, M.S, Rahman, S, Amer, O.E, Al‐Attas, O.S, Alfawaz, H, Tripathi, G, Sabico, S., Chrousos, G.P, McTernan, P.G and Piya, M.K 2015. Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2. European Journal of Clinical Investigation. https://doi.org/10.1111/eci.12468
Novel splicing variants of recepteur d'origine nantais (RON) tyrosine kinase involving exons 15–19 in lung cancer
Krishnaswamy, S, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2015. Novel splicing variants of recepteur d'origine nantais (RON) tyrosine kinase involving exons 15–19 in lung cancer. Lung Cancer. https://doi.org/10.1016/j.lungcan.2015.12.002
Field cancerisation in colorectal cancer: A new frontier or pastures past?
Patel, A, Tripathi, G, Gopalakrishnan, K, Williams, N and Arasaradnam, R.P 2015. Field cancerisation in colorectal cancer: A new frontier or pastures past? World Journal of Gastroenterology. https://doi.org/10.3748/wjg.v21.i13.3763
Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells
Murphy, A, Jackisch, L., Azharian, S, Aladel, A, Barker, G, Tripathi, G, Chappell, M and McTernan, P 2014. Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells. bioscientifica. https://doi.org/10.1530/endoabs.44.P191
Systemic triglycerides as a key determinant of TLR regulated inflammatory risk in human adipose tissue post bariatric surgical intervention and weight loss
Kumsaiyai, W, Al-Daghri, N, Kyrou, I, Vrbikova, J, Hainer, V, Fried, M, Sramkova, P, Barber, T, S Kumar, Tripathi, G and McTernan, P 2014. Systemic triglycerides as a key determinant of TLR regulated inflammatory risk in human adipose tissue post bariatric surgical intervention and weight loss. bioscientifica. https://doi.org/10.1530/endoabs.34.P238
Tunicamycin-induced ER stress mediates mitochondrial dysfunction in human adipocytes
Jackisch, L, Murphy, A, Al-Daghri, N, McTernan, P, Randeva, H and Tripathi, G 2014. Tunicamycin-induced ER stress mediates mitochondrial dysfunction in human adipocytes. bioscientifica. https://doi.org/10.1530/endoabs.44.P193
Methyl donor deficiency due to low vitamin b12 impairs insulin signalling in human adipocytes by down regulating AKT pathway via PTEN and TRB3
Adaikalakoteswari, A, Finer, S, Voyias, P.D, McCarthy, M, Vatish, M, Moore, J, Smart-Halajko, M, Bawazeer, N, Al-Daghri, N.M, McTernan, P.G, Hitman, G.A, Saravanan, P and Tripathi, G 2014. Methyl donor deficiency due to low vitamin b12 impairs insulin signalling in human adipocytes by down regulating AKT pathway via PTEN and TRB3. American Diabetes Association.
Vitamin B12 deficiency induces adipocyte dysfunction via enhanced cholesterol biosynthesis, unfolded protein response and associated epigenetic marks
Finer, S, Hitman, G.A, Saravanan, P and Tripathi, G 2014. Vitamin B12 deficiency induces adipocyte dysfunction via enhanced cholesterol biosynthesis, unfolded protein response and associated epigenetic marks. Norwich Research ParK.
The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes
Piya, Milan K, Harte, A. L, Sivakumar, K, Tripathi, G, Voyias, P. D, James, S, Sabico, S, Al-Daghri, N, M, Saravanan, P, Barber, T. M, Kumar, S, Vatish, M and McTernan, P. G 2014. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. American Journal of Physiology Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00308.2013
Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes.
Adaikalakoteswari, A, Jayashri, R, Sukumar, N, Venkataraman, H, Pradeepa, R, Gokulakrishnan, K, Anjana, R.M, McTernan, P.G, Tripathi, G, Patel, V and Kumar, S. 2014. Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes. Cardiovascular Diabetology. https://doi.org/10.1186/s12933-014-0129-4
Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white caucasians living in the UK
Adaikalakoteswari, A, Vatish, M, Lawson, A, Wood, C, Sivakumar, K, McTernan, P, Webster, C, Anderson, N, Yajnik, C, Tripathi, G and Saravanan, P 2015. Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white caucasians living in the UK. Nutrients. https://doi.org/10.3390/nu7042401
Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly.
Reddy, N.L, Peng, C, Carreira, M.C, Halder, L, Hattersley, J, Piya, M.K, Tripathi, G, Randeva, H.S, Casanueva, F.F, McTernan, P.G and Kumar, S 2014. Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly. Cinical Endocrinology. https://doi.org/10.1111/cen.12652
Maternal inheritance of circulating irisin in humans.
Al-Daghri, N.M, Al-Attas, O.S, Alokail, M.S, Alkharfy, K.M, Yousef, M, Vinodson, B, Amer, O.E, Alnaami, A.M, Sabico, S, Tripathi, G and Piya, M.K. 2014. Maternal inheritance of circulating irisin in humans. Clincal Science. https://doi.org/10.1042/CS20130426
Surface charge visualization at viable living cells
Perry, D, Paulose Nadappuram, B, Momotenko, D, Voyias, P.D, Page, A, Tripathi, G, Frenguelli, B.G and Unwin, P.R 2016. Surface charge visualization at viable living cells. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.5b13153
Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery.
de la Escalera, L.M, Kyrou, I, Vrbikova, J, Hainer, V, Sramkova, P, Fried, M, Piya, M.K, Kumar, S, Tripathi, G and McTernan, P.G 2017. Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery. BMC Medicine. https://doi.org/10.1186/s12916-017-0797-5
Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation.
Reddy, N.L, Jones, T.A, Wayte, S.C, Adesanya, O, Sankar, S, Yeo, Y.C, Tripathi, G, McTernan, P.G, Randeva, H.S, Kumar, S and Hutchinson, C.E 2014. Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/jc.2013-2036
Postprandial effect of a high-fat meal on endotoxemia in Arab women with and without insulin-resistance-related diseases.
Al-Disi, D, A-Daghri, N, Khan, N, Alfadda, A, Sallam, R, Alsaif, M, Sabico, S, Tripathi, G and McTernan, P 2015. Postprandial effect of a high-fat meal on endotoxemia in Arab women with and without insulin-resistance-related diseases. Nutrients. https://doi.org/10.3390/nu7085290
Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes.
Hu, J, Kyrou, I, Tan, B.K, Dimitriadis, G.K, Ramanjaneya, M, Tripathi, G, Patel, V, James, S, Kawan, M, Chen, J and Randeva, H.S 2016. Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes. Endocrinology. https://doi.org/10.1210/en.2015-1944
Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects
Al-Daghri, N.M, Rahman, S, Sabico, S, Yakout, S, Wani, K, Al-Attas, O.S, Saravanan, P, Tripathi, G, McTernan, P.G and Alokail, M.S 2016. Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients. https://doi.org/10.3390/nu8090460