CORRELATION BETWEEN THREE LO NG NON-CODING RNA GENE EXPRESSION AND PATHOLOGICAL RESPONSE IN BREAST CANCER PATIENTS RECEIVING NEOADJUVANT CHEMOTHERAPY IN EGYPT

Abstract

: Breast cancer (BC) is the second cancer in global cancer incidence with an estimated 2.3 million new cases compromising 11.6% of all cancer cases, and the fourth leading cause of cancer mortality worldwide (6.9% of all cancer deaths). Numerous studies have reported the relationship between long non-coding RNAs (lncRNAs) and multi drug resistance (MDR) in BC, whether this therapy was chemotherapy, targeted therapy or endocrine treatment, where each has a specific lncRNA that is responsible for the resistance mechanism.

Aim: This study aimed at improving the plan of management of breast cancer patients receiving neoadjuvant chemotherapy by better understanding the factors that may affect the pathological response via studying the possible role of the three lncRNAs (BC032585, AK291479, and U79293) as predictive biomarkers and/or therapeutic targets.

Patients and methods: This retrospective comparative study was conducted on 120 BC patients recruited from both clinical oncology departments at Faculty of Medicine Suez Canal University and Dar el Salam cancer hospital (Harmel) in the period between October 2020 to October 2021. Molecular analysis was done to assess the gene expression levels of the three lncRNAs AK291479, U79293 and BC032585 via comparative real time PCR technique using the paraffin blocks of the BC patients receiving neoadjuvant chemotherapy (NACTH) at two different stages of treatment (paraffin blocks of the biopsy before receiving neoadjuvant chemotherapy and those of surgery; after receiving NACTH).

Results: The lncRNA BC0332585 showed overexpression in both groups under study with median and interquartile (IQR) values equivalent to 6.12 (4.16 – 7.18) among the pathologic complete response (pCR) group and 6.38 (4.82 – 7.72) among partial pathological response (pPR) group and both were statistically significant. The lncRNA AK291479 showed under expression among both groups under study, with pCR expression levels equivalent to -4.33 (-6.90 – 0.02) and pPR

 -6.26 (-9.45– -3.53), and both were statistically significant. Finally, the lncRNA U79293 showed under expression among the pCR group where expression levels ranged between -1.45 (-3.12 – 0.16) and those with pPR expression ranged from -0.83 (-3.36 – 0.70) and both were statistically significant.

Conclusion: Although there is a statistically significant correlation between the expression levels of the three lncRNAs understudy; AK291479, U79293 and BC032585 in both pCR and pPR groups, the three tested lncRNAs showed the same pattern of expression in both pCR and pPR groups suggesting that they cannot be utilized as predictive markers for pathological response after NACTH. Meanwhile many lncRNAs showed to be key regulators in BC drug resistance via modulating its pathways at epigenetic, transcriptional, and post-transcriptional levels in many studies, our study didn’t prove the significance of the three lncRNAs; AK291479, U79293 and BC032585 as promising biomarkers in BC management as predictive and or prognostic biomarkers, however they showed a possible potential for being used as therapeutic biomarkers.