MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

<div><p>Introduction</p><p>MicroRNAs are small, non coding regulatory molecules containing approximately 21 to 25 nucleotides. They function as controllers of expression at post transcriptional levels of most human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study is to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17, miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible interaction in triple-negative and non triple-negative primary breast cancers based on clinical outcome.</p><p>Methods</p><p>60 triple-negative and non triple-negative breast cancer cases, along with their corresponding normal samples were investigated in relation to the expression of the seven studied miRNAs using qPCR Syber Green.</p><p>Results</p><p>We observed that miR-21, miR-146a and miR-182 were significantly over expressed in triple negative breast cancer. Moreover, miR-10b, miR-21 and miR-182 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma while only miR-10b was associated with grade III in non triple negative breast cancer cases. Almost all the analyzed microRNAs were strongly associated with patients’ genico-obstetric history in non triple negative breast cancer cases except for miR-34a. All the studied microRNAs were strongly correlated with the use of the contraceptive pills in non triple negative breast cancer groups. The additive effect of hormonal factors in triple negative breast cancer cases showed an association with all the studied miRs except for miR-34 and miR-146a.</p><p>Conclusion</p><p>The studied microRNAs are strongly influenced by environmental factors especially with hormonal patients’ history. Moreover, miR-10b, miR-21 and miR-182 could be defined as biomarkers in breast cancer to predict both lymph node metastases and grade III occurrence.</p></div

Comparison of miRs expression levels in normal and tumor mammary tissues among triple negative and non triple negative mammary tumors.

<p>Blot letters indicate <i>p</i> Value <0.01, SD: standard deviation.</p><p>Comparison of miRs expression levels in normal and tumor mammary tissues among triple negative and non triple negative mammary tumors.</p

Spearman’s rank correlation coefficient between microRNA fold expression levels in triple-negative and non triple negative breast cancer cases.

<p>Underlined letters concern the correlation between miRs across triple negative breast cancer. The non underlined letters concern the correlation between miRs across non triple negative breast cancer. Bold letters with *represent <i>P</i> value <0.05; Bold letters with **represent <i>P</i> value <0.01.</p><p>Spearman’s rank correlation coefficient between microRNA fold expression levels in triple-negative and non triple negative breast cancer cases.</p

Tumorigenesis and targeted genes of the selected microRNAs in breast cancer and other human malignancies.

<p>Tumorigenesis and targeted genes of the selected microRNAs in breast cancer and other human malignancies.</p

Comparison of miRs fold expression levels according to 0 or 1 hormonal risk factor and to the hormonal additive effect (age of first menstruation, age at the first pregnancy, use of the contraceptive pills and breastfeeding) among triple negative breast patients.

<p><i>P</i> value in blot <0.05, SD: standard deviation.</p><p>Comparison of miRs fold expression levels according to 0 or 1 hormonal risk factor and to the hormonal additive effect (age of first menstruation, age at the first pregnancy, use of the contraceptive pills and breastfeeding) among triple negative breast patients.</p

List of the analyzed microRNAs.

<p>List of the analyzed microRNAs.</p

Comparison of the mean fold expression levels (Log 2 transformed) of the different studied microRNAs between both triple negative and non triple negative breast tumors.

<p>Blot letters with *indicate p Value <0.05; Blot letters with **indicate <i>p</i> Value <0.01, SD: standard deviation.</p><p>Comparison of the mean fold expression levels (Log 2 transformed) of the different studied microRNAs between both triple negative and non triple negative breast tumors.</p

Comparison of the clinico-pathological features along with patients’ genico-obstetric history among triple negative and non triple negative mammary tumors.

<p><i>P</i> in blot <0.05 is significant. CI = 95%; 2- Compared between (CCI and CLI+CCIS+CS); 4-Compared between (III and I+II); 6- Compared between (T1–T2 and T0+T3–T4); 7- Compared between <12 years and >12 years; 8- Compared between <25 years and >25 years; 9 -Compared between 0 and one at least; 10- Compared between No and Yes; 11- Compared between No and Yes; 12- Compared between <30 and >30.</p><p>Comparison of the clinico-pathological features along with patients’ genico-obstetric history among triple negative and non triple negative mammary tumors.</p