The debatable presence of PIWI‐interacting RNAs in invasive breast cancer

Abstract

Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could be improved. Lately, Piwi‐interacting RNAs (piRNAs) have been introduced as potential cancer biomarkers, however, due to the recently raised challenges in piRNA annotations, further evaluation of piRNAs’ involvement in cancer is required. We performed small RNA sequencing in 227 fresh‐frozen breast tissue samples from the Eastern Finnish Kuopio Breast Cancer Project material to study the presence of piRNAs in BC and their associations with the clinicopathological features and outcome of BC patients. We observed the presence of three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) in our samples. The actual species of these RNAs however remain uncertain. All three small RNAs were upregulated in grade III tumors and DQ596932 additionally in estrogen receptor negative tumors. Furthermore, patients with estrogen receptor positive BC and higher DQ571955 had shorter relapse‐free survival and poorer BC‐specific survival, thus indicating DQ571955 as a candidate predictive marker for radiotherapy response in estrogen receptor positive BC. DQ596932 showed possible prognostic value in BC, whereas DQ570994 was identified as a candidate predictive marker for tamoxifen and chemotherapy response. These three small RNAs appear as candidate biomarkers for BC, which could after further investigation provide novel approaches for the treatment of therapy resistant BC. Overall, our results indicate that the prevalence of piRNAs in cancer is most likely not as comprehensive as has been previously thought.

Piwi-Interacting RNAs: A New Class of Regulator in Human Breast Cancer

“…Those aberrantly expressed piRNAs in breast cancer including piR-4987, piR-021285, piR-823, piR-932, piR-36712, piR-016658 and piR-016975 may held potential to be developed as biomarkers and/or therapeutic targets in breast cancer. Our recent study also identified 415 piRNA sequences from the medium of luminal subtype of human breast cancer cell MCF-7, in which 27 piRNAs showed deregulation by prooncogene cyclin D1 (28) (51). Three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) were detected in the tumor samples, all showing upregulation in grade III tumors.…”

“…Furthermore, patients with estrogen receptor positive and DQ571955 high had shorter relapse-free survival, suggesting DQ571955 as a potential marker for predicting radiotherapy response in estrogen receptor positive breast cancer. In addition, DQ570994 showed potential for predicting tamoxifen and chemotherapy response (51). In triple negative breast cancer (TNBC), neoadjuvant chemotherapy (NACT) is increasingly applied to the therapy management due to its positive association with response rates of patients.…”

Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

“…DQ570994 was a candidate predictive marker for tamoxifen and chemotherapy response. Overall, these three small RNAs have their own values as biomarkers for BC [ 72 ]. Haug et al investigated the prognostic value of the mRNA-miRNA-lncRNA network in TNBC using the GEO2R tool.…”

Overview of non-coding RNAs in breast cancers

“…A study by Kärkkäinen et al. found that lncRNAs are involved in the signalling pathways of breast cancer [89] . Flores-Huerta et al.…”