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ARTICLE

Ultrasound genomics related mitochondrial gene signature for prognosis and neoadjuvant chemotherapy resistance in triple negative breast cancer

HUAFANG HUANG1,2,#, GUILIN WANG3,#, DONGYUN ZENG4,5, LUZ ANGELA TORRES-DE LA ROCHE2, RUI ZHUO1,2, RUDY LEON DE WILDE2, WANWAN WANG6, ULF D. KAHLERT7,*, WENJIE SHI7,*
1 Department of Breast Surgery, EUSOMA Certificate Breast Cancer Center (No.1037/00), Guilin TCM Hospital of China, Guilin, 541002, China
2 University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, 26121, Germany
3 Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541002, China
4 Clinicopathological Diagnosis & Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China
5 Key Laboratory of Tumor Molecular Pathology of Guangxi Higher Education Institutes, Baise, 533000, China
6 Department of Breast and Thyroid Surgery, Xuzhou No.1 People’s Hospital, Xuzhou, 221000, China
7 Molecular and Experimental Surgery, University Clinic for General-, Visceral-, Vascular- and Trans-Plantation Surgery, Medical Faculty University Hospital Magdeburg, Otto-von Guericke University, Magdeburg, 39120, Germany
* Corresponding Author: ULF D. KAHLERT. Email: email; WENJIE SHI. Email: email
# These two authors contributed equally to this work
(This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)

Oncology Research https://doi.org/10.32604/or.2024.054642

Received 03 June 2024; Accepted 26 September 2024; Published online 15 October 2024

Abstract

Background: Neoadjuvant chemotherapy (NAC) significantly enhances clinical outcomes in patients with triple-negative breast cancer (TNBC); however, chemoresistance frequently results in treatment failure. Consequently, understanding the mechanisms underlying resistance and accurately predicting this phenomenon are crucial for improving treatment efficacy. Methods: Ultrasound images from 62 patients, taken before and after neoadjuvant therapy, were collected. Mitochondrial-related genes were extracted from a public database. Ultrasound features associated with NAC resistance were identified and correlated with significant mitochondrial-related genes. Subsequently, a prognostic model was developed and evaluated using the GSE58812 dataset. We also assessed this model alongside clinical factors and its ability to predict immunotherapy response. Results: A total of 32 significant differentially expressed genes in TNBC across three groups indicated a strong correlation with ultrasound features. Univariate and multivariate Cox regression analyses identified six genes as independent risk factors for TNBC prognosis. Based on these six mitochondrial-related genes, we constructed a TNBC prognostic model. The model’s risk scores indicated that high-risk patients generally have a poorer prognosis compared to low-risk patients, with the model demonstrating high predictive performance (p = 0.002, AUC = 0.745). This conclusion was further supported in the test set (p = 0.026, AUC = 0.718). Additionally, we found that high-risk patients exhibited more advanced tumor characteristics, while low-risk patients were more sensitive to common chemotherapy drugs and immunotherapy. The signature-related genes also predicted immunotherapy response with a high accuracy of 0.765. Conclusion: We identified resistance-related features from ultrasound images and integrated them with genomic data, enabling effective risk stratification of patients and prediction of the efficacy of neoadjuvant chemotherapy and immunotherapy in patients with TNBC.

Keywords

Ultrasound genomics; Mitochondrial; Breast cancer; Neoadjuvant; Resistance

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