Sonographic Features of Triple-Negative Breast Carcinomas Are Correlated With mRNA-lncRNA Signatures and Risk of Tumor Recurrence

Abstract

Background: To determine a correlation between mRNA and lncRNA signatures, sonographic features, and risk of recurrence in triple-negative breast cancers (TNBC).

Methods: We retrospectively reviewed the data from 114 TNBC patients having undergone transcriptome analysis. The risk of tumor recurrence was determined based on the correlation between transcriptome profiles and recurrence-free survival. Ultrasound (US) features were described according to the Breast Imaging Reporting and Data System. Multivariate logistic regression analysis determined the correlation between US features and risk of recurrence. The predictive value of sonographic features in determining tumor recurrence was analyzed using receiver operating characteristic curves.

Results: Three mRNAs (CHRDL1, FCGR1A, and RSAD2) and two lncRNAs (HIF1A-AS2 and AK124454) were correlated with recurrence-free survival in patients with TNBC. Among the three mRNAs, two were upregulated (FCGR1A and RSAD2) and one was downregulated (CHRDL1) in TNBCs. LncRNAs HIF1A-AS2 and AK124454 were upregulated in TNBCs. Based on these signatures, an integrated mRNA-lncRNA model was established using Cox regression analysis to determine the risk of tumor recurrence. Benign-like sonographic features, such as regular shape, circumscribed margin, posterior acoustic enhancement, and no calcifications, were associated with HIF1A-AS2 expression and high risk of tumor recurrence (P<0.05). Malignant-like features, such as irregular shape, uncircumscribed margin, no posterior acoustic enhancement, and calcifications, were correlated with CHRDL1 expression and low risk of tumor recurrence (P<0.05).

Conclusions: Sonographic features and mRNA-lncRNA signatures in TNBCs represent the risk of tumor recurrence. Taken together, US may be a promising technique in determining the prognosis of patients with TNBC.

Keywords: long non-coding RNA; messenger RNA; triple-negative breast cancer; tumor recurrence; ultrasound.

Figure 1

Association between the expression profile of mRNA CHRDL1 and sonographic features of TNBCs. The high expression of CHRDL1 is significantly associated with malignant sonographic features of irregular shape, absence of posterior acoustic enhancement, and presence of angular/spiculated margin. * indicates significant difference between the two groups with and without the specific sonographic feature.

Figure 2

Association between the expression profile of lncRNA HIF1A-AS2 and sonographic features of TNBCs. The high expression of HIF1A-AS2 is significantly associated with benign sonographic features of regular shape, presence of posterior acoustic enhancement, absence of angular/spiculated margin, and no calcification. * indicates significant difference between the two groups with and without the specific sonographic feature.

Figure 3

Illustration of TNBC in a 66-year-old female patient. (A, B) Irregular shape, angular margin and posterior acoustic shadow in sonogram (BI-RADS:4C); (C) Histological grade II in HE staining (original magnification × 400); (D) Twenty percent Ki-67 expression in IHC staining (original magnification × 200).

Figure 4

Illustration of TNBC in a 29-year-old female patient. (A, B) Regular shape, circumscribed margin and posterior acoustic enhancement in sonogram (BI-RADS:4A); (C) Histological grade III in HE staining (original magnification × 400); (D) Eighty percent Ki-67 expression in IHC staining (original magnification × 200).

Figure 5

ROC curve for the prediction model of risk of recurrence based on sonographic features, clinicopathological characteristics, and the combined sonographic-clinical-pathological parameters of TNBCs.