miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis

Abstract

We sought to systematically evaluate the diagnostic and prognostic value of miR-203 in patients with colorectal cancer. To explore the diagnostic performance of miR-203, eligible studies were identified from biomedical databases. Based on these results, 11 studies were pooled and included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios of miR-203 were 0.83 (95% confidence interval, CI: 0.78–0.86), 0.80 (95% CI: 0.77–0.83), and 19.27 (95% CI: 7.23–51.36) for the diagnosis of colorectal cancer. The area under the curve for miR-203 for diagnosing colorectal cancer was 0.89. Patients with higher expression of tissue miR-203 had poor overall survival (pooled hazard ratio: 1.63; 95% CI: 1.03–2.57, P=0.04), but serum miR-203 was not predictive (pooled hazard ratio: 1.59; 95% CI: 0.31–8.12, P=0.58). The miR-203 values of tissue and serum merged together may perhaps predict superior overall survival (pooled hazard ratio: 1.62; 95% CI: 0.93–2.82), but the effect was not significant (P=0.09).

Keywords:

• colorectal cancer
• CRC
• diagnosis
• miR-203
• prognosis

Supplementary materials

Figure S1 miR-203 diagnostic analysis based on the eligible studies.

Notes: (A) Fagan’s nomogram describes the possibility of miR-203 assay to confirm or exclude cancer patients. In detail, for any people with a pretest probability of 20% to have cancers, if the miR-203 test in cancer detection was positive, the posttest probability to have cancer would rise to 54%; while a negative result of miR-203 assay meant the posttest probability would drop to 5% for the same people. Hence, miR-203 assay may play an important role as an initial screening method for cancer. (B) The overall distribution of studies is summarized in the likelihood matrix. Each corresponds to a study.^⑦, Sheinerman et al³⁴ was on the bottom left side of the matrix, indicating a sensitive “rule out” test. However, it reported reasonable sensitivity with incorporation bias from knowledge of a desaturation study outcome.

Abbreviations: RUQ, upper right quadrant; LUQ, upper left quadrant; RLQ, lower right quadrant; LLQ, lower left quadrant; LRN, negative likelihood ratio; LRP, positive likelihood ratio; NLR, negative likelihood ratio; PLR, positive likelihood ratio; prob, probability.

Figure S2 The sensitivity analysis based on the studies for prognosis of OS.

Notes: Forest plot for the sensitivity analysis shows the results of the meta-analysis did not change after the removal of any one paper. (A) The nine survival data from CRC tissue and serum; (B) six survival data from CRC serum.

Abbreviations: CRC, colorectal cancer; OS, overall survival.

Figure S3 The publication bias based on the studies for prognosis of OS.

Notes: Publication bias from Begg’s test is shown by funnel plots. Every point represents one study. (A) The nine survival data from CRC tissue and serum; (B) six survival data from CRC serum.

Abbreviations: CRC, colorectal cancer; Inhr, In hazard ratio; OS, overall survival; SE, standard error.

References

• HurKToiyamaYOkugawaYCirculating microRNA-203 predicts prognosis and metastasis in human colorectal cancerGut201766465466526701878
   PubMed Web of Science ®Google Scholar
• DengBWangBFangJMiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2Sci Rep201662830127376958
   PubMed Web of Science ®Google Scholar
• TaoKYangJGuoZPrognostic value of miR-221-3p, miR-342-3p and miR-491-5p expression in colon cancerAm J Transl Res20146439140125075256
   PubMed Web of Science ®Google Scholar
• BovellLCShanmugamCPutchaBDThe prognostic value of microRNAs varies with patient race/ethnicity and stage of colorectal cancerClin Cancer Res201319143955396523719259
   PubMed Web of Science ®Google Scholar
• SchetterAJLeungSYSohnJJMicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinomaJAMA2008299442543618230780
   PubMed Web of Science ®Google Scholar
• ToiyamaYHurKTakahashiMSerum MIR-200c and mir-203 are novel prognostic and metastasis-predictive biomarkers in patients with colorectal cancer (CRC)Gastroenterology20121425S533
   Google Scholar
• CroceCSchetterAHarrisCMir-106a for diagnosing poor survival prognosis colon adenocarcinoma EP2436782A12013 Available from: http://www.google.gm/patents/EP2436782B8Accessed February 8, 2017
   Google Scholar

Acknowledgments

We thank the Charlesworth Author Service’s language editing service for editing the manuscript.

Disclosure

The authors report no conflicts of interest in this work.