Proteome analysis of formalin-fixed paraffin-embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas.
FFPE
LC-MS/MS
colon adenoma
formalin-fixed paraffin-embedded
label-free quantification
proteomics
sessile serrated adenoma (SSA/P)
traditional serrated adenoma (TSA)
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
17
07
2019
revised:
23
10
2019
accepted:
12
11
2019
pubmed:
16
11
2019
medline:
8
7
2020
entrez:
16
11
2019
Statut:
ppublish
Résumé
Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label-free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA/Ps) and 17 normal colonic mucosa samples, archived as formalin-fixed paraffin-embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well-individualized clusters composed of all the CADs (15/15) and most of the SSA/Ps (13/17), respectively. This is consistent with the fact that CADs and SSA/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal/TGFβ pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA/Ps or from normal mucosa evolving through a process related to the CAD pathway. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Substances chimiques
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
251-261Informations de copyright
© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Références
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-767.
Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 330-337.
Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 2010; 138: 2088-2100.
JE IJ, Vermeulen L, Meijer GA, et al. Serrated neoplasia-role in colorectal carcinogenesis and clinical implications. Nat Rev Gastroenterol Hepatol 2015; 12: 401-409.
Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol 2009; 4: 343-364.
Snover DC, Batts KP. Serrated colorectal neoplasia. Surg Pathol Clin 2010; 3: 207-240.
Torlakovic EE, Gomez JD, Driman DK, et al. Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA). Am J Surg Pathol 2008; 32: 21-29.
Borras E, San Lucas FA, Chang K, et al. Genomic landscape of colorectal mucosa and adenomas. Cancer Prev Res (Phila) 2016; 9: 417-427.
Cho H, Hashimoto T, Yoshida H, et al. Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp. Histopathology 2018; 73: 672-680.
Fang M, Ou J, Hutchinson L, et al. The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island methylator phenotype. Mol Cell 2014; 55: 904-915.
Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138: 2073-2087.
Kambara T, Simms LA, Whitehall VL, et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 2004; 53: 1137-1144.
Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50: 113-130.
Bettington ML, Walker NI, Rosty C, et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol 2015; 28: 414-427.
Tsai JH, Liau JY, Lin YL, et al. Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis. Mod Pathol 2014; 27: 1375-1385.
Bettington ML, Chetty R. Traditional serrated adenoma: an update. Hum Pathol 2015; 46: 933-938.
Erichsen R, Baron JA, Hamilton-Dutoit SJ, et al. Increased risk of colorectal cancer development among patients with serrated polyps. Gastroenterology 2016; 150: 895-902.e5.
Gonzalo DH, Lai KK, Shadrach B, et al. Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. J Pathol 2013; 230: 420-429.
Delker DA, McGettigan BM, Kanth P, et al. RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers. PLoS One 2014; 9: e88367.
Kanth P, Bronner MP, Boucher KM, et al. Gene signature in sessile serrated polyps identifies colon cancer subtype. Cancer Prev Res (Phila) 2016; 9: 456-465.
Deeb SJ, Tyanova S, Hummel M, et al. Machine learning-based classification of diffuse large B-cell lymphoma patients by their protein expression profiles. Mol Cell Proteomics 2015; 14: 2947-2960.
Kinzler KW, Nilbert MC, Su LK, et al. Identification of FAP locus genes from chromosome 5q21. Science 1991; 253: 661-665.
Wisniewski JR, Zougman A, Nagaraj N, et al. Universal sample preparation method for proteome analysis. Nat Methods 2009; 6: 359-362.
Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 2008; 26: 1367-1372.
Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43: e47.
Marisa L, de Reynies A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013; 10: e1001453.
Pasmant E, Parfait B, Luscan A, et al. Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you have a large gene with loss of function mutations? Eur J Hum Genet 2015; 23: 596-601.
Jass JR, Baker K, Zlobec I, et al. Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a 'fusion' pathway to colorectal cancer. Histopathology 2006; 49: 121-131.
Gibson JA, Hahn HP, Shahsafaei A, et al. Expression in hyperplastic and serrated colonic polyps: lack of specificity of MUC6. Am J Surg Pathol 2011; 35: 742-749.
Renaud F, Mariette C, Vincent A, et al. The serrated neoplasia pathway of colorectal tumors: identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential. Int J Cancer 2016; 138: 1472-1481.
Sajanti SA, Vayrynen JP, Sirnio P, et al. Annexin A10 is a marker for the serrated pathway of colorectal carcinoma. Virchows Arch 2015; 466: 5-12.
Sakuma R, Ohnishi Yi Y, Meno C, et al. Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion. Genes Cells 2002; 7: 401-412.
Kitisin K, Saha T, Blake T, et al. Tgf-Beta signaling in development. Sci STKE 2007; 2007: cm1.
Davis H, Irshad S, Bansal M, et al. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med 2015; 21: 62-70.
Hamada H, Meno C, Watanabe D, et al. Establishment of vertebrate left-right asymmetry. Nat Rev Genet 2002; 3: 103-113.
Gao S, Yan L, Wang R, et al. Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat Cell Biol 2018; 20: 721-734.
Smillie CS, Biton M, Ordovas-Montanes J, et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell 2019; 178: 714-730.
Cross W, Kovac M, Mustonen V, et al. The evolutionary landscape of colorectal tumorigenesis. Nat Ecol Evol 2018; 2: 1661-1672.
Kim JH, Kim KJ, Rhee YY, et al. Gastric-type expression signature in serrated pathway-associated colorectal tumors. Hum Pathol 2015; 46: 643-656.
Saito T, Niida A, Uchi R, et al. A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer. Nat Commun 2018; 9: 2884.
Thirlwell C, Will OC, Domingo E, et al. Clonality assessment and clonal ordering of individual neoplastic crypts shows polyclonality of colorectal adenomas. Gastroenterology 2010; 138: 1441-1454 1454.e1-7.
Owen RP, White MJ, Severson DT, et al. Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands. Nat Commun 2018; 9: 4261.
Chen C, Shen MM. Two modes by which Lefty proteins inhibit nodal signaling. Curr Biol 2004; 14: 618-624.
Gehart H, Clevers H. Tales from the crypt: new insights into intestinal stem cells. Nat Rev Gastroenterol Hepatol 2019; 16: 19-34.
Haramis AP, Begthel H, van den Born M, et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 2004; 303: 1684-1686.
Vayrynen SA, Vayrynen JP, Klintrup K, et al. Ectopic crypt foci in conventional and serrated colorectal polyps. J Clin Pathol 2016; 69: 1063-1069.
Teale FW, Weber G. Ultraviolet fluorescence of the aromatic amino acids. Biochem J 1957; 65: 476-482.
Zhang X, Smits AH, van Tilburg GB, et al. Proteome-wide identification of ubiquitin interactions using UbIA-MS. Nat Protoc 2018; 13: 530-550.
Wieczorek S, Combes F, Lazar C, et al. DAPAR & ProStaR: software to perform statistical analyses in quantitative discovery proteomics. Bioinformatics 2017; 33: 135-136.
Determan CE Jr. Optimal algorithm for metabolomics classification and feature selection varies by dataset. Int J Biol 2015; 7: 100.