Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma.
OBJECTIVE
Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression.


METHODS
Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression.


RESULTS
PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (/Z-score/ >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this microRNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone.


CONCLUSIONS
IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients.
Schetter
Aaron J
AJ
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Nguyen
Giang Huong
GH
Bowman
Elise D
ED
Mathé
Ewy A
EA
Yuen
Siu Tsan
ST
Hawkes
Jason E
JE
Croce
Carlo M
CM
Leung
Suet Yi
SY
Harris
Curtis C
CC
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D016207:Cytokines / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D016207:Cytokines; C524940:MIRN21 microRNA, human; D035683:MicroRNAs