Cancer Research and Treatment

Original Articles

Breast cancer

Machine Learning–Based Prognostic Gene Signature for Early Triple-Negative Breast Cancer: Ju Won Kim, Jonghyun Lee, Sung Hak Lee, Sangjeong Ahn, Kyong Hwa Park; Cancer Res Treat. 2025;57(3):731-740. Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.937

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to develop a machine learning–based approach to identify prognostic gene signatures for early-stage triple-negative breast cancer (TNBC) using next-generation sequencing data from Asian populations.
Materials and Methods
We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.
Results
We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.
Conclusion
This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

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RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer: Tian-Hao Weng, Min-Ya Yao, Xiang-Ming Xu, Chen-Yu Hu, Shu-Hao Yao, Yi-Zhi Liu, Zhi-Gang Wu, Tao-Ming Tang, Pei-Fen Fu, Ming-Hai Wang, Hang-Ping Yao; Cancer Res Treat. 2020;52(3):973-986. Published online April 22, 2020; DOI: https://doi.org/10.4143/crt.2019.726

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment.
Materials and Methods
We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model.
Results
Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060.
Conclusion
RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.

Citations

Citations to this article as recorded by

Humanized dual-targeting antibody–drug conjugates specific to MET and RON receptors as a pharmaceutical strategy for the treatment of cancers exhibiting phenotypic heterogeneity
Minghai Wang, Qi Ma, Sreedhar Reddy Suthe, Rachel E. Hudson, Jing-ying Pan, Constantinos Mikelis, Miao-jin Zhu, Zhi-gang Wu, Dan-rong Shi, Hang-ping Yao
Acta Pharmacologica Sinica.2025; 46(5): 1375. CrossRef
Nuclear translocation of RON receptor tyrosine kinase. New mechanistic and functional insights
Yi-Lin Chen, Chien-An Chu, Jiu-Yao Wang, Wan-Li Chen, Yi-Wen Wang, Chung-Liang Ho, Chung-Ta Lee, Nan-Haw Chow
Cytokine & Growth Factor Reviews.2025; 81: 9. CrossRef
The Development of meso-Methyl-BODIPY Conjugates with Boc-seco-CBI and Cabozantinib: The Practical Challenges of Red-Light-Activated Prodrugs for Anticancer PDT
Natalia S. Kuzmina, Galina P. Gribova, Elizaveta M. Pnachina, Lubov V. Krylova, Ekaterina A. Fedotova, Irina V. Balalaeva, Alexey Yu. Fedorov, Vasilii F. Otvagin
Bioconjugate Chemistry.2025; 36(9): 2061. CrossRef
MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence
Kai Wu, Jia Ji, Jingying Pan, Miaojin Zhu, Jiale Zhang, Ting Sun, Dan Lv, Mudan Wei, Minghai Wang, Hangping Yao
Cell Communication and Signaling.2025;[Epub] CrossRef
c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer
Jieun Park, Eun Sol Chang, Ji-Yeon Kim, Chaithanya Chelakkot, Minjung Sung, Ji-Young Song, Kyungsoo Jung, Ji Hye Lee, Jun Young Choi, Na Young Kim, Hyegyeong Lee, Mi-Ran Kang, Mi Jeong Kwon, Young Kee Shin, Yeon Hee Park, Yoon-La Choi
Breast Cancer Research.2024;[Epub] CrossRef
MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature
Pei Yuan, Xuemin Xue, Tian Qiu, Jianming Ying
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer
Sara K. Jaradat, Nehad M. Ayoub, Ahmed H. Al Sharie, Julia M. Aldaod
Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Recent advancement in developing small molecular inhibitors targeting key kinase pathways against triple-negative breast cancer
Rajibul Islam, Khor Poh Yen, Nur Najihah ’Izzati Mat Rani, Md. Selim Hossain
Bioorganic & Medicinal Chemistry.2024; 112: 117877. CrossRef
TYRO3 and EPHA2 Expression Are Dysregulated in Breast Cancer
Ananda Cristina Fernandes de Aguiar, Nancy Cristina Ferraz de Lucena Ferreira, Maria Amelia Carlos Souto Maior Borba, Darley de Lima Ferreira Filho, Glauber Moreira Leitão, Luiz Alberto Mattos, José Luiz de Lima Filho, Danyelly Bruneska Gondim Martins
Cell Biochemistry and Function.2024;[Epub] CrossRef
The MET Oncogene Network of Interacting Cell Surface Proteins
Simona Gallo, Consolata Beatrice Folco, Tiziana Crepaldi
International Journal of Molecular Sciences.2024; 25(24): 13692. CrossRef
Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials
Kasshish Mehta, Mangala Hegde, Sosmitha Girisa, Ravichandran Vishwa, Mohammed S. Alqahtani, Mohamed Abbas, Mehdi Shakibaei, Gautam Sethi, Ajaikumar B. Kunnumakkara
Military Medical Research.2024;[Epub] CrossRef
Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells
María Luisa Sánchez-León, Carlos Jiménez-Cortegana, Silvia Silva Romeiro, Carmen Garnacho, Luis de la Cruz-Merino, Daniel J. García-Domínguez, Lourdes Hontecillas-Prieto, Víctor Sánchez-Margalet
International Journal of Molecular Sciences.2023; 24(6): 5208. CrossRef
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Satyam Rajput, Kaivalya A. Deo, Tanmay Mathur, Giriraj Lokhande, Kanwar Abhay Singh, Yuxiang Sun, Daniel L. Alge, Abhishek Jain, Tapasree Roy Sarkar, Akhilesh K. Gaharwar
Bioprinting.2022; 25: e00187. CrossRef
The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies
Alex Cazes, Betzaira G. Childers, Edgar Esparza, Andrew M. Lowy
Cancers.2022; 14(8): 2037. CrossRef
Antibody-drug Conjugate PCMC1D3-Duocarmycin SA as a Novel Therapeutic Entity for Targeted Treatment of Cancers Aberrantly Expressing MET Receptor Tyrosine Kinase
Rachel Hudson, Hang-Ping Yao, Sreedhar Reddy Suthe, Dhavalkumar Patel, Ming-Hai Wang
Current Cancer Drug Targets.2022; 22(4): 312. CrossRef
Pharmaceutical strategies in the emerging era of antibody-based biotherapeutics for the treatment of cancers overexpressing MET receptor tyrosine kinase
Hang-Ping Yao, Xiang-Min Tong, Ming-Hai Wang
Drug Discovery Today.2021; 26(1): 106. CrossRef
Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions
Minru Liao, Jin Zhang, Guan Wang, Leiming Wang, Jie Liu, Liang Ouyang, Bo Liu
Journal of Medicinal Chemistry.2021; 64(5): 2382. CrossRef
The MSP‐RON pathway regulates liver fibrosis through transforming growth factor beta‐dependent epithelial–mesenchymal transition
Tianhao Weng, Dong Yan, Danrong Shi, Miaojin Zhu, Yizhi Liu, Zhigang Wu, Taoming Tang, Linwei Zhu, Hong Zhang, Hangping Yao, Lanjuan Li
Liver International.2021; 41(8): 1956. CrossRef
MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase
Huilin Ou, Keda Chen, Hongcheng Wu, Yuan Seng Wu
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RON Mediates Tumor‐Promoting Effects in Endometrial Adenocarcinoma
Qin Yu, Jianzhang Wang, Tiantian Li, Xinxin Xu, Xinyue Guo, Shaojie Ding, Libo Zhu, Gen Zou, Yichen Chen, Xinmei Zhang, Bing Wang
BioMed Research International.2021;[Epub] CrossRef
Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer
Zainab Al-Taie, Mark Hannink, Jonathan Mitchem, Christos Papageorgiou, Chi-Ren Shyu
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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
Wei Peng, Jian-Di Li, Jing-Jing Zeng, Xiao-Ping Zou, Deng Tang, Wei Tang, Min-Hua Rong, Ying Li, Wen-Bin Dai, Zhong-Qing Tang, Zhen-Bo Feng, Gang Chen
Cancer Cell International.2020;[Epub] CrossRef

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PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy: Sanxing Guo, Sibylle Loibl, Gunter von Minckwitz, Silvia Darb-Esfahani, Bianca Lederer, Carsten Denkert; Cancer Res Treat. 2020;52(3):689-696. Published online February 4, 2020; DOI: https://doi.org/10.4143/crt.2019.497

Abstract PDF PubReader ePub

Purpose
PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CAmutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Materials and Methods
A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.
Results
Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).
Conclusion
TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

Citations

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