Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression.
Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors.
Sillars-Hardebol
Anke H
AH
Department of Pathology (Tumor Profiling Unit), VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Carvalho
Beatriz
B
de Wit
Meike
M
Postma
Cindy
C
Delis-van Diemen
Pien M
PM
Mongera
Sandra
S
Ylstra
Bauke
B
van de Wiel
Mark A
MA
Meijer
Gerrit A
GA
Fijneman
Remond J A
RJ
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D000097869:Polo-Like Kinase 1
D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta; D000097869:Polo-Like Kinase 1; C576917:AURKA protein, human