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Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis

Authors: Yu-Shui Ma, Tao Huang, Xiao-Ming Zhong, Hong-Wei Zhang, Xian-Ling Cong, Hong Xu, Gai-Xia Lu, Fei Yu, Shao-Bo Xue, Zhong-Wei Lv, Da Fu

Published in: Molecular Cancer | Issue 1/2018

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Abstract

Background

Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.

Methods

Here, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.

Results

We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1R202H and PARP4V458I) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.

Conclusions

Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.

Trial registration

ClinicalTrials, NCT02917707. Registered 28 September 2016, https://​clinicaltrials.​gov/​ct2/​show/​NCT02917707.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRef Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRef
2.
go back to reference Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–89.CrossRef Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–89.CrossRef
3.
go back to reference Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;513:333–9.CrossRef Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;513:333–9.CrossRef
4.
go back to reference Liu Y, Zhang X, Han C, Wan G, Huang X, Ivan C, et al. TP53 loss creates therapeutic vulnerability in colorectal cancer. Nature. 2015;520:697–701.CrossRef Liu Y, Zhang X, Han C, Wan G, Huang X, Ivan C, et al. TP53 loss creates therapeutic vulnerability in colorectal cancer. Nature. 2015;520:697–701.CrossRef
5.
go back to reference Network TCGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487:330–7.CrossRef Network TCGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487:330–7.CrossRef
6.
go back to reference Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, et al. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014;513:382–7.CrossRef Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, et al. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014;513:382–7.CrossRef
7.
go back to reference Neilson KA, Ali N, Muralidharan S, Mirzaei M, Mariani M, Assadourian G, et al. less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics. 2011;11:535–53.CrossRef Neilson KA, Ali N, Muralidharan S, Mirzaei M, Mariani M, Assadourian G, et al. less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics. 2011;11:535–53.CrossRef
8.
go back to reference Bouckaert RR, Drummond AJ. bModelTest: phylogenetic model averaging. Mol Biol Evol. 2003;20:1978–85.CrossRef Bouckaert RR, Drummond AJ. bModelTest: phylogenetic model averaging. Mol Biol Evol. 2003;20:1978–85.CrossRef
9.
go back to reference Polisetty RV, Gautam P, Sharma R, Harsha HC, Nair SC, Gupta MK, et al. LC-MS/MS analysis of differentially expressed glioblastoma membrane proteome reveals altered calcium signaling and other protein groups of regulatory functions. Mol Cell Proteomics. 2012;11:M111.013565.CrossRef Polisetty RV, Gautam P, Sharma R, Harsha HC, Nair SC, Gupta MK, et al. LC-MS/MS analysis of differentially expressed glioblastoma membrane proteome reveals altered calcium signaling and other protein groups of regulatory functions. Mol Cell Proteomics. 2012;11:M111.013565.CrossRef
10.
go back to reference Luber CA, Cox J, Lauterbach H, Fancke B, Selbach M, Tschopp J, et al. Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. Immunity. 2010;32:279–89.CrossRef Luber CA, Cox J, Lauterbach H, Fancke B, Selbach M, Tschopp J, et al. Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. Immunity. 2010;32:279–89.CrossRef
11.
go back to reference Forero-Castro M, Robledo C, Benito R, Abáigar M, África Martín A, Arefi M, et al. Genome-wide DNA copy number analysis of acute lymphoblastic leukemia identifies new genetic markers associated with clinical outcome. PLoS One. 2016;11:e0148972.CrossRef Forero-Castro M, Robledo C, Benito R, Abáigar M, África Martín A, Arefi M, et al. Genome-wide DNA copy number analysis of acute lymphoblastic leukemia identifies new genetic markers associated with clinical outcome. PLoS One. 2016;11:e0148972.CrossRef
12.
go back to reference Abuín JM, Pichel JC, Pena TF, Amigo J. BigBWA: approaching the burrows-wheeler aligner to big data technologies. Bioinformatics. 2015;31:4003–5.PubMed Abuín JM, Pichel JC, Pena TF, Amigo J. BigBWA: approaching the burrows-wheeler aligner to big data technologies. Bioinformatics. 2015;31:4003–5.PubMed
13.
go back to reference Cibulskis K, McKenna A, Fennell T, Banks E, DePristo M, Getz G. ContEst: estimating cross-contamination of human samples in next-generation sequencing data. Genome Res. 2010;20:1297–303.CrossRef Cibulskis K, McKenna A, Fennell T, Banks E, DePristo M, Getz G. ContEst: estimating cross-contamination of human samples in next-generation sequencing data. Genome Res. 2010;20:1297–303.CrossRef
14.
go back to reference Li H, Durbin R. PAnnBuilder: an R package for assembling proteomic annotation data. Bioinformatics. 2009;25:1094–5.CrossRef Li H, Durbin R. PAnnBuilder: an R package for assembling proteomic annotation data. Bioinformatics. 2009;25:1094–5.CrossRef
15.
go back to reference Wang K, Li M, Hakonarson H. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nucleic Acids Res. 2010;38:e164.CrossRef Wang K, Li M, Hakonarson H. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nucleic Acids Res. 2010;38:e164.CrossRef
16.
go back to reference Tindall EA, Speight G, Petersen DC, Padilla EJ, Hayes VM. Novel Plexor SNP genotyping technology: comparisons with TaqMan and homogenous MassEXTEND MALDI-TOF mass spectrometry. Hum Mutat. 2007;28:922–7.CrossRef Tindall EA, Speight G, Petersen DC, Padilla EJ, Hayes VM. Novel Plexor SNP genotyping technology: comparisons with TaqMan and homogenous MassEXTEND MALDI-TOF mass spectrometry. Hum Mutat. 2007;28:922–7.CrossRef
17.
go back to reference Ongen H, Andersen CL, Bramsen JB, Oster B, Rasmussen MH, Ferreira PG, et al. Putative cis-regulatory drivers in colorectal cancer. Nature. 2014;512:87–90.CrossRef Ongen H, Andersen CL, Bramsen JB, Oster B, Rasmussen MH, Ferreira PG, et al. Putative cis-regulatory drivers in colorectal cancer. Nature. 2014;512:87–90.CrossRef
18.
go back to reference Oh BY, Hong HK, Lee WY, Cho YB. Animal models of colorectal cancer with liver metastasis. Cancer Lett. 2017;387(114–20.CrossRef Oh BY, Hong HK, Lee WY, Cho YB. Animal models of colorectal cancer with liver metastasis. Cancer Lett. 2017;387(114–20.CrossRef
19.
go back to reference Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47:320–9.CrossRef Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47:320–9.CrossRef
20.
go back to reference Sayagués JM, Corchete LA, Gutiérrez ML, Sarasquete ME, Del M, Bengoechea O, et al. Genomic characterization of liver metastases from colorectal cancer patients. Oncotarget. 2016;7:72908–22.CrossRef Sayagués JM, Corchete LA, Gutiérrez ML, Sarasquete ME, Del M, Bengoechea O, et al. Genomic characterization of liver metastases from colorectal cancer patients. Oncotarget. 2016;7:72908–22.CrossRef
21.
go back to reference Zhou M, Yang H, Learned RM, Tian H, Ling L. Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis. Nat Commun. 2017;8:15433.CrossRef Zhou M, Yang H, Learned RM, Tian H, Ling L. Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis. Nat Commun. 2017;8:15433.CrossRef
22.
go back to reference Cheng D, Zhao S, Tang H, Zhang D, Sun H, Yu F, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget. 2016;7:45199–213.PubMedPubMedCentral Cheng D, Zhao S, Tang H, Zhang D, Sun H, Yu F, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget. 2016;7:45199–213.PubMedPubMedCentral
23.
go back to reference Chen LG, Xia YJ, Cui Y. Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation. Oncol Rep. 2017;38:100–8.CrossRef Chen LG, Xia YJ, Cui Y. Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation. Oncol Rep. 2017;38:100–8.CrossRef
24.
go back to reference Han D, Wang M, Ma N, Xu Y, Jiang Y, Gao X. Long noncoding RNAs: novel players in colorectal cancer. Cancer Lett. 2015;361:13–21.CrossRef Han D, Wang M, Ma N, Xu Y, Jiang Y, Gao X. Long noncoding RNAs: novel players in colorectal cancer. Cancer Lett. 2015;361:13–21.CrossRef
25.
go back to reference Ouzounova M, Lee E, Piranlioglu R, El Andaloussi A, Kolhe R, Demirci MF, et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun. 2017;8:14979.CrossRef Ouzounova M, Lee E, Piranlioglu R, El Andaloussi A, Kolhe R, Demirci MF, et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun. 2017;8:14979.CrossRef
Metadata
Title
Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis
Authors
Yu-Shui Ma
Tao Huang
Xiao-Ming Zhong
Hong-Wei Zhang
Xian-Ling Cong
Hong Xu
Gai-Xia Lu
Fei Yu
Shao-Bo Xue
Zhong-Wei Lv
Da Fu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0890-1

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