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HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer

Authors Zhang J, Zhang S, Gao S, Ma Y, Tan X, Kang Y, Ren W

Received 17 January 2020

Accepted for publication 10 March 2020

Published 24 March 2020 Volume 2020:12 Pages 2209—2222

DOI https://doi.org/10.2147/CMAR.S246349

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan


Jing Zhang,1 Shuo Zhang,2 Song Gao,3 Yan Ma,1 Xueying Tan,1 Ye Kang,4 Weidong Ren1

1Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 2Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 3Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China; 4Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China

Correspondence: Weidong Ren
Department of Ultrasound, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang City 110004, People’s Republic of China
Email renwdcmu01@163.com

Purpose: To investigate the relationship between hypoxia-inducible factor 1-alpha (HIF-1α), Twist family BHLH transcription factor 1 (TWIST-1), and β 1 integrin (ITGB-1) expression and tumor stiffness, and evaluate performance of HIF-1α, TWIST-1, and ITGB-1 alone and in combination with Ki-67 for predicting pathological responses to neoadjuvant chemotherapy (NACT) in breast cancer (BC).
Patients and Methods: This was a prospective cohort study of 104 BC patients receiving NACT. Tumor stiffness and oxygen score (OS) were evaluated before NACT by shear-wave elastography and optical imaging; HIF-1α, TWIST-1, ITGB-1, and Ki-67 expression were quantitatively assessed by immunohistochemistry of paraffin-embedded tumor samples obtained by core needle biopsy. Indexes were compared among different residual cancer burden (RCB) groups, and associations of HIF-1α, TWIST-1, ITGB-1, and Ki-67 with tumor stiffness and OS were examined. The value of HIF-1α, TWIST-1, ITGB-1, and Ki-67, and a possible new combined index (predRCB) for predicting NACT responses was assessed by receiver operating characteristic (ROC) curves.
Results: HIF-1α, TWIST-1, and ITGB-1 expression were positively correlated with tumor stiffness and negatively with OS. Area under the ROC curves (AUCs) measuring the performance of HIF-1α, TWIST-1, ITGB-1, and Ki-67 for predicting responses to NACT were 0.81, 0.85, 0.79, and 0.80 for favorable responses, and 0.83, 0.86, 0.84, and 0.85 for resistant responses, respectively. PredRCB showed better prediction than the other individual indexes for favorable responses (AUC = 0.88) and resistant responses (AUC = 0.92).
Conclusion: HIF-1α, TWIST-1, ITGB-1, and Ki-67 performed well in predicting favorable responses and resistance to NACT, and predRCB improved the predictive power of the individual indexes. These results support individualized treatment of BC patients receiving NACT.

Keywords: HIF-1α, TWIST-1, ITGB-1, neoadjuvant chemotherapy, breast cancer, prediction

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