A Three lncRNA Set: AC009975.1, POTEH-AS1 and AL390243.1 as Nodal Efficacy Biomarker of Neoadjuvant Therapy for HER-2 Positive Breast Cancer.

Zhao Bi,Xing-Guo Song,Peng-Fei Qiu,Yong-Sheng Wang,Yue Zhang,Li Xie,Xian-Rang Song,Peng Chen

doi:10.3389/fonc.2021.779140

Zhao Bi, Xing-Guo Song + Show 6 more

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https://doi.org/10.3389/fonc.2021.779140

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Abstract

PurposeThe study aimed to explore whether the expression of lncRNAs in primary tumors could predict nodal efficacy after neoadjuvant therapy (NAT) for HER2+ breast cancer.MethodsTotal RNA was extracted from HER2+ breast cancer tissues before NAT (n=103) and from 48 pairs of cancers and para-cancers tissues that did not receive NAT. Different lncRNAs were selected by microarray, validated by qPCR, and analyzed to illuminate their potential as nodal efficacy biomarkers after NAT.ResultsOur results demonstrated that three lncRNA sets, lncRNA-AL390243.1, POTEH-AS1, and lncRNA-AC009975.1, were up-regulated in non-apCR tissues. The AUC value was 0.789 (95%CI: 0.703-0.876). The multivariate logistic regression analysis identified the expression of lncRNA-AL390243.1 (OR 5.143; 95% CI: 1.570-16.847), tumor type (OR 0.144; 95% CI: 0.024-0.855), and nodal stage (OR 0.507; 95% CI: 0.289-0.888) as independent predictors for apCR after NAT in HER2+ patients (all p<0.05). Then the three predictors were used to create a predictive nomogram. The AUC value was 0.859 (95%CI: 0.790-0.929). The calibration curve showed a satisfactory fit between predictive and actual observation based on internal validation with a bootstrap resampling frequency of 1000. Patients with higher expression of lncRNA-AL390243.1 had worse survival. LncRNA-AL390243.1 was up-regulated more in the nodal positive subgroup than in the nodal negative subgroup (p=0.0271).ConclusionThe lncRNA-AL390243.1, POTEH-AS1, and lncRNA-AC009975.1 were upregulated in non-apCR breast cancer tissues. These three lncRNAs might have the potential to be used as predictive biomarkers of nodal efficacy of HER2+ breast cancer. Further studies are required to illuminate the underlying molecular mechanisms further.

Highlights

Neoadjuvant therapy (NAT) has become an adapt therapy for patients with inoperable as well as some high-risk breast cancer, such as stage II–III HER-2 positive (HER2+) and triple-negative breast cancer (TNBC) [1, 2]
These results indicated the great potential of the expression of lncRNAAL390243.1, tumor type, and nodal stage as nodal efficacy biomarkers for HER2+ breast cancer
The breast pathological complete response (bpCR) was not completely consistent with axillary nodal pathological complete response (apCR). As this difference was most significant in the HER2+ subtype, we aim to explore whether there are differential lncRNAs in primary tumors that could predict apCR after NAT

Summary

Introduction

Neoadjuvant therapy (NAT) has become an adapt therapy for patients with inoperable as well as some high-risk breast cancer, such as stage II–III HER-2 positive (HER2+) and triple-negative breast cancer (TNBC) [1, 2]. The result of the Z1071 trial showed that for patients with initial cN+ and ycN0 disease after NAT, using combined tracers (radiolabeled colloid and blue dye) and detecting > 2 negative sentinel lymph nodes (SLN), the false negative rate (FNR) of SLNB after NAT could reduce to 10% or less [7]. ALND remains the standard option in axillary management since the overall false negative rate (FNR) of SLNB after NAT is still a concern. Given these concerns, optimizing patient selection might be necessary to support the use of SLNB as an alternative to ALND after NAT [9]

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