Skip to content

Research at St Andrews

Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers

Research output: Contribution to journalArticle

Author(s)

Romina Briffa, In Hwa Um, Dana Faratian, Ying Zhou, Arran K Turnbull, Simon P Langdon, David James Harrison

School/Research organisations

Abstract

Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.
Close

Details

Original languageEnglish
Article numbere0144708
Number of pages29
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - 17 Dec 2015

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Raman spectroscopy investigation of biochemical changes in tumour spheroids with ageing and after treatment with staurosporine

    Jamieson, L. E., Harrison, D. J. & Campbell, C. J. 20 Sep 2018 (Accepted/In press) In : Journal of Biophotonics. In press, e201800201

    Research output: Contribution to journalArticle

  2. Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

    Lindsay, C. R. , Shaw, E. C. , Blackhall, F. , Blyth, K. G. , Brenton, J. D. , Chaturvedi, A. , Clarke, N. , Dick, C. , Evans, T. R. J. , Hall, G. , Hanby, A. M. , Harrison, D. J. , Johnston, S. R. D. , Mason, M. D. , Morton, D. , Newton-Bishop, J. , Nicholson, A. G. , Oien, K. A. , Popat, S. , Rassl, D. & 9 others Sharpe, R., Taniere, P., Walker, I., Wallace, W. A., West, N. P., Butler, R., Gonzalez de Castro, D., Griffiths, M. & Johnson, P. W. M. 5 Sep 2018 In : ESMO Open. 3, 6, 9 p., e000408

    Research output: Contribution to journalArticle

  3. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

    Warren, A. Y. & Harrison, D. 19 Aug 2018 In : World Journal of Urology. First Online, 14 p.

    Research output: Contribution to journalReview article

  4. Podocyte injury elicits loss and recovery of cellular forces

    Haley, K., Kronenberg, N. M., Liehm, P., Elshani, M., Bell, C., Harrison, D. J., Gather, M. C. & Reynolds, P. A. 27 Jun 2018 In : Science Advances. 4, 6, 9 p., eaap8030

    Research output: Contribution to journalArticle

Related by journal

  1. 16S rRNA gene metabarcoding and TEM reveals different ecological strategies within the genus Neogloboquadrina (planktonic foraminifer)

    Bird, C., Darling, K. F., Russell, A. D., Fehrenbacher, J. S., Davis, C. V., Free, A. & Ngwenya, B. T. 29 Jan 2018 In : PLoS One. 13, 1, 26 p., e0191653

    Research output: Contribution to journalArticle

  2. Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib

    Ladds, M. J. G. W., Pastor-Fernández, A., Popova, G., van Leeuwen, I. M. M., Eng, K. E., Drummond, C. J., Johansson, L., Svensson, R., Westwood, N. J., McCarthy, A. R., Tholander, F., Popa, M., Lane, D. P., McCormack, E., McInerney, G. M., Bhatia, R. & Laín, S. 23 Apr 2018 In : PLoS One. 13, 4, 21 p., e0195956

    Research output: Contribution to journalArticle

  3. Body density of humpback whales (Megaptera novaengliae) in feeding aggregations estimated from hydrodynamic gliding performance

    Narazaki, T., Isojunno, S., Nowacek, D. P., Swift, R., Friedlaender, A. S., Ramp, C., Smout, S., Aoki, K., Deecke, V. B., Sato, K. & Miller, P. J. O. 12 Jul 2018 In : PLoS ONE. 13, 7, 23 p., e0200287

    Research output: Contribution to journalArticle

  4. Compositionality in animals and humans

    Townsend, S. W., Engesser, S., Stoll, S., Zuberbühler, K. & Bickel, B. 15 Aug 2018 In : PLoS One. 16, 8, 7 p., e2006425

    Research output: Contribution to journalArticle

  5. Context or composition: how does neighbourhood deprivation impact upon adolescent smoking behaviour?

    Morris, T., Manley, D. & van Ham, M. 8 Feb 2018 In : PLoS One. 13, 2, 16 p., e0192566

    Research output: Contribution to journalArticle

Related by journal

  1. PLoS One (Journal)

    Cresswell, W. (Reviewer)
    23 May 2018

    Activity: Publication peer-review and editorial workPeer review of manuscripts

  2. PLoS ONE (Journal)

    Dritschel, B. (Member of editorial board)
    May 2018 → …

    Activity: Publication peer-review and editorial workEditor of research journal

  3. PLoS One (Journal)

    Young, S. (Reviewer)
    7 Jun 201719 Jun 2017

    Activity: Publication peer-review and editorial workPeer review of manuscripts

  4. PLoS ONE (Journal)

    Schwarz-Linek, U. (Reviewer)
    Mar 2017

    Activity: Publication peer-review and editorial workPeer review of manuscripts

  5. PLoS One (Journal)

    Hughes, D. J. (Reviewer)
    2014 → …

    Activity: Publication peer-review and editorial workPeer review of manuscripts

ID: 234874675