title: Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs.
abstract: MicroRNAs (miRNAs) enable colonic epithelial cells to acquire malignant characteristics and metastatic capabilities. Recently, cancer relevant miRNAs deregulated during disease progression have also been identified in tumor-associated stroma.By combining laser-microdissection (LMD) with high-throughput screening and high-sensitivity quantitation techniques, miRNA expression in colorectal cancer (CRC) specimens and paired normal colonic tissue was independently characterized in stromal and epithelial tissue compartments. Notably, deregulation of the key oncogene miR-21 was identified exclusively as a stromal phenomenon and miR-106a, an epithelial phenomenon in the malignant state.MiRNAs identified in this study successfully distinguished CRC from normal tissue and metastatic from non-metastatic tumor specimens. Furthermore, in a separate cohort of 50 consecutive patients with CRC, stromal miR-21 and miR-556 and epithelial miR-106a expression predicted short disease free survival (DFS) and overall survival (OS) in stage II disease: miR-21 (DFS: HR = 2.68, p = 0.015; OS: HR = 2.47, p = 0.029); miR-556 (DFS: HR = 2.60, p = 0.018); miR-106a (DFS: HR = 2.91, p = 0.008; OS: HR = 2.25, p = 0.049); combined (All High vs. All Low. DFS: HR = 5.83, p = 0.002; OS: HR = 4.13, p = 0.007).These data support the notion that stromal as well as epithelial miRNAs play important roles during disease progression, and that mapping patterns of deregulated gene expression to the appropriate tumor strata may be a valuable aid to therapeutic decision making in CRC.
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.|Department of Surgery, Southampton University Hospital NHS Trust, Southampton, UK.
authors: Marc D
authors: MD
authors: Bullock
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.
authors: Karen
authors: K
authors: Pickard
authors: Bioinformatics Unit, London Research Institute, Cancer Research UK, London, UK.
authors: Richard
authors: R
authors: Mitter
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.
authors: A Emre
authors: AE
authors: Sayan
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.|Department of Surgery, Southampton University Hospital NHS Trust, Southampton, UK.
authors: John N
authors: JN
authors: Primrose
authors: Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Cristina
authors: C
authors: Ivan
authors: Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: George A
authors: GA
authors: Calin
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.
authors: Gareth J
authors: GJ
authors: Thomas
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.
authors: Graham K
authors: GK
authors: Packham
authors: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.|Department of Surgery, Southampton University Hospital NHS Trust, Southampton, UK.
authors: Alex H
authors: AH
authors: Mirnezami
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D042282:Microdissection; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012306:Risk; D012867:Skin / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: colorectal cancer; microRNA; stroma; tumor microenvironment