Kanchi Rama, Aparna R Bitla, Narendra Hulikal, Mutheeswaraiah Yootla, Lakshmi Amancharla Yadagiri, T Asha, M Manickavasagam, PVLN Srinivasa Rao

Assessment of serum microRNA-21 and miRNA-205 as diagnostic markers for stage I and II breast cancer in Indian population

  • Oncology
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Abstract Background: Current markers (carcinoembryonic antigen [CEA] and carbohydrate antigen 15-3 [CA15-3]) lack sensitivity in diagnosis of breast cancer. The aberrantly expressed circulating miRNAs were shown as diagnostic markers in breast cancer. However, there are very few studies from the Indian population. We studied the diagnostic utility of miRNA-21, miRNA-155 and miRNA-205 compared to CEA and CA15-3 in stage I and II breast cancer patients. Materials and Methods: Sixty newly diagnosed women with stage I/II breast cancer and 20 healthy controls were recruited. Expression of circulating miRNAs was studied using reverse transcription-polymerase chain reaction, whereas CEA and CA 15-3 were analyzed by enzyme-linked immunosorbent assay. Results: miRNA-21 and miRNA-155 were upregulated, miRNA-205 down-regulated (P < 0.05) and serum CEA and CA15-3 levels increased in breast cancer patients (P < 0.001). Receiver operating characteristic curve analysis showed significant area under curve (AUC) for all markers (0.656 to 0.993; P = 0.015 to <0.001) validating their diagnostic potential. Unlike CEA and CA15-3, miRNAs retained their sensitivity even at higher cut-offs (95% CI of mean). Logistic regression analysis showed significant association between disease and marker positivity for miRNA-21 and miRNA-205 but not for miRNA-155. Combining CA15-3 with miRNAs did not improve their diagnostic performance. However, combining CEA with either miRNA-21 (AUC = 0.742; P < 0.001 versus AUC = 0.656; P = 0.018) or miRNA-205 (AUC = 0.733; P < 0.001 versus AUC = 0.700; P < 0.001) increased its diagnostic performance. Conclusion: Our study shows miRNA-21 and miRNA-205, are useful as diagnostic markers for breast cancer in the Indian population and combination of these miRNAs with CEA but not with CA 15-3 improved their diagnostic performance.

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