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MicroRNAsÑnoncoding RNA molecules that regulate the translation of genesÑmay function as diagnostic biomarkers and therapeutic targets in cancer. Schetter and colleagues examined microRNA expression patterns in colon tumors and paired nontumorous tissue from 2 independent cohorts of patients with sporadic colon adenocarcinoma. The authors identified expression patterns that were associated with colon tumor formation, response to chemotherapy, and cancer-specific survival. In particular, tumors with a high expression of microRNA miR-21 were associated with a poor response to adjuvant chemotherapy and poor patient survival.
Aaron J. Schetter, PhD, MPH; Suet Yi Leung, MD; Jane J. Sohn, PhD; Krista A. Zanetti, PhD, MPH; Elise D. Bowman, MS; Nozomu Yanaihara, MD, PhD; Siu Tsan Yuen, MD; Tsun Leung Chan, MD; Dora L. W. Kwong, MD; Gordon K. H. Au, MD; Chang-Gong Liu, PhD; George A. Calin, MD, PhD; Carlo M. Croce, MD; Curtis C. Harris, MD
JAMA.Ê2008;299(4):425-436.
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Infection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e.g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post-translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer. Recent discovery of an interaction between microRNAs and innate immunity during inflammation has further strengthened the association between inflammation and cancer.
S. Perwez Hussain, Curtis C. Harris, International Journal of Cancer,
Volume 121, Issue 11, Pages 2373-2380.
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Results: A 15Ðcytokine gene signature in noncancerous lung tissue primarily reflected the lymph node status of 80 lung adenocarcinoma patients, whereas the gene signature of the corresponding lung tumor tissue was associated with prognosis independent of lymph node status. Cytokine Lung Adenocarcinoma Survival Signature of 11 genes (CLASS-11), a refined 11-gene signature, accurately classified patients, including those with stage I disease, according to risk of death from adenocarcinoma. CLASS-11 prognostic classification was statistically significantly associated with survival and was an independent prognostic factor for stage I patients (hazard ratio for death in the high-risk CLASS-11 group compared with the low-risk CLASS-11 reference group = 7.46, 95% confidence interval = 2.14 to 26.05; P = .002). CLASS-11 also classified patients in the validation set according to risk of recurrence.
Conclusion: CLASS-11, which consists of genes for pro- and anti-inflammatory cytokines, identifies stage I lung adenocarcinoma patients who have a poor prognosis.
Seike M, Yanaihara N, Bowman ED, Zanetti KA, Budhu A, Kumamoto K, Mechanic LE, Matsumoto S, Yokota J, Shibata T, Sugimura H, Gemma A, Kudoh S, Wang XW, Harris CC., J Natl Cancer Inst. 2007 Aug 15;99(16):1257-69. Epub 2007 Aug 8.
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The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared with European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical variables. We also evaluated 18 nontumor prostate tissues from seven African-American and 11 European-American patients.
Tiffany A. Wallace1, Robyn L. Prueitt1, Ming Yi3, Tiffany M. Howe1, John W. Gillespie2, Harris G. Yfantis4, Robert M. Stephens3, Neil E. Caporaso5, Christopher A. Loffredo6 and Stefan Ambs,Cancer Research 68, 927-936, February 1, 2008
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MicroRNAs (miRNAs) have been used as cancer-related biomarkers. Hepatocellular carcinoma
(HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and
postsurgical recurrence. We investigated whether the expression of certain miRNAs are
associated with HCC metastasis. We examined the miRNA expression profiles of 482 cancerous
and noncancerous specimens from radical resection of 241 patients with HCC. Using
a supervised algorithm and a clinically well-defined cohort of 131 cases, we built a unique
20-miRNA metastasis signature that could significantly predict (P < 0.001) primary HCC
tissues with venous metastases from metastasis-free solitary tumors with 10-fold crossvalidation.
Anuradha Budhu,1* Hu-Liang Jia,1,2* Marshonna Forgues,1 Chang-Gong Liu,3 David Goldstein,4 Amy Lam,5
Krista A. Zanetti,6 Qing-Hai Ye,2 Lun-Xiu Qin,2 Carlo M. Croce,3 Zhao-You Tang,2 and Xin Wei Wang
HEPATOLOGY, Month 2008
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molecular mechanisms of carcinogenesis including human liver, lung and colon carcinogenesis, hypoxia-driven carcinogenesis and tumor progression; and 
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