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Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs.

Bullock MD, Pickard K, Mitter R, Sayan AE, Primrose JN, Ivan C, Calin GA, Thomas GJ, Packham GK, Mirnezami AH - Oncotarget (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.

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.

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MiRNAs significantly differentially expressed by a factor > 2 (p < 0.05) in (A) CRC stroma vs. paired normal colonic stroma; and (B) CRC epithelium vs. paired normal colonic epitheliumQuantimiR™-qPCR analysis was performed using total RNA extracted from fresh-frozen LMD tissue from 10 patients with CRC.
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Figure 1: MiRNAs significantly differentially expressed by a factor > 2 (p < 0.05) in (A) CRC stroma vs. paired normal colonic stroma; and (B) CRC epithelium vs. paired normal colonic epitheliumQuantimiR™-qPCR analysis was performed using total RNA extracted from fresh-frozen LMD tissue from 10 patients with CRC.

Mentions: In total, 5 miRNAs were significantly upregulated and 13 miRNAs significantly downregulated in CRC stroma compared with paired normal tissue (Figure 1A). Amongst the miRNA candidates upregulated more than X2-fold were miR-19a and -19b and miR-21, which are recognized oncogenes [22–26].


Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs.

Bullock MD, Pickard K, Mitter R, Sayan AE, Primrose JN, Ivan C, Calin GA, Thomas GJ, Packham GK, Mirnezami AH - Oncotarget (2015)

MiRNAs significantly differentially expressed by a factor > 2 (p < 0.05) in (A) CRC stroma vs. paired normal colonic stroma; and (B) CRC epithelium vs. paired normal colonic epitheliumQuantimiR™-qPCR analysis was performed using total RNA extracted from fresh-frozen LMD tissue from 10 patients with CRC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466683&req=5

Figure 1: MiRNAs significantly differentially expressed by a factor > 2 (p < 0.05) in (A) CRC stroma vs. paired normal colonic stroma; and (B) CRC epithelium vs. paired normal colonic epitheliumQuantimiR™-qPCR analysis was performed using total RNA extracted from fresh-frozen LMD tissue from 10 patients with CRC.
Mentions: In total, 5 miRNAs were significantly upregulated and 13 miRNAs significantly downregulated in CRC stroma compared with paired normal tissue (Figure 1A). Amongst the miRNA candidates upregulated more than X2-fold were miR-19a and -19b and miR-21, which are recognized oncogenes [22–26].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Southampton, UK.

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.

Show MeSH
Related in: MedlinePlus