{"title":"Identification of Biomarkers of Shrinkage Modes After Neoadjuvant Therapy in HER-2 Positive Breast Cancer.","authors":"Zhao Bi, Yue Zhang, Xian-Rang Song, Wen-Hao Zheng, Peng Chen, Peng-Fei Qiu, Yan-Bing Liu, Yong-Jin Lu, Xing-Guo Song, Yong-Sheng Wang","doi":"10.1097/JS9.0000000000002349","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>A nomogram to predict shrinkage modes after neoadjuvant therapy (NAT) was constructed in HER-2 positive (HER2 +) breast cancer. The value and mechanism of targeting long non-coding RNA (lncRNA) as efficacy prediction biomarker was also evaluated.</p><p><strong>Methods: </strong>All enrolled patients received six cycles of chemotherapy (docetaxel + carboplatin) and anti-HER-2 dual-targeted therapy (Trastuzumab + Pertuzumab) before surgery. According to pathological 3D models of residual tumor from 71 HER2 + patients, shrinkage modes were divided into concentric shrinkage mode (CSM) and non-CSM (NCSM). LncRNAs in core biopsy tissues in the CSM and NCSM groups were selected by microarray and validated by RT-PCR. A nomogram was constructed to predict shrinkage modes after NAT in combination with clinical-pathological and transcriptome signatures. Cell proliferation was used CCK-8 and colony formation assay. PAPIS Kit was used to perform nuclear and cytoplasmic separation. The cell drug resistance assays were to explore the value of paclitaxel. The ChIRP-MS assay was to search RNA-binding proteins and verified by WB. Cell cycle analysis was carried out by flow cytometry.</p><p><strong>Results: </strong>Independent predictors of NCSM were lymph nodes downstaging after NAT, mammographic malignant calcification, hormone receptor expression, and RUVBL1-AS1 expression. A nomogram was constructed in combination with these predictors, which showed an area under the curve of 0.883, supporting the predictive power of the method. Overexpression of RUVBL1-AS1 inhibited HER2 + cells proliferation. Overexpression of RUVBL1-AS1 increased the number of cells in G1/S phase and decreased that of cells in G2 phase. RUVBL1-AS1 increased paclitaxel resistance and downregulate VCP expression. RUVBL1-AS1 affects cell cycle progression by downregulating VCP, resulting in the reduction of cells in G2/M phase, thereby weakening the sensitivity to paclitaxel.</p><p><strong>Conclusion: </strong>The nomogram could accurately predict shrinkage modes after NAT, and may help guide the individualized selection of breast conserving surgery candidates after NAT. RUVBL1-AS1 might be a promising therapeutic target of paclitaxel-based chemotherapy inHER2 + breast cancer.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":12.5000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/JS9.0000000000002349","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: A nomogram to predict shrinkage modes after neoadjuvant therapy (NAT) was constructed in HER-2 positive (HER2 +) breast cancer. The value and mechanism of targeting long non-coding RNA (lncRNA) as efficacy prediction biomarker was also evaluated.
Methods: All enrolled patients received six cycles of chemotherapy (docetaxel + carboplatin) and anti-HER-2 dual-targeted therapy (Trastuzumab + Pertuzumab) before surgery. According to pathological 3D models of residual tumor from 71 HER2 + patients, shrinkage modes were divided into concentric shrinkage mode (CSM) and non-CSM (NCSM). LncRNAs in core biopsy tissues in the CSM and NCSM groups were selected by microarray and validated by RT-PCR. A nomogram was constructed to predict shrinkage modes after NAT in combination with clinical-pathological and transcriptome signatures. Cell proliferation was used CCK-8 and colony formation assay. PAPIS Kit was used to perform nuclear and cytoplasmic separation. The cell drug resistance assays were to explore the value of paclitaxel. The ChIRP-MS assay was to search RNA-binding proteins and verified by WB. Cell cycle analysis was carried out by flow cytometry.
Results: Independent predictors of NCSM were lymph nodes downstaging after NAT, mammographic malignant calcification, hormone receptor expression, and RUVBL1-AS1 expression. A nomogram was constructed in combination with these predictors, which showed an area under the curve of 0.883, supporting the predictive power of the method. Overexpression of RUVBL1-AS1 inhibited HER2 + cells proliferation. Overexpression of RUVBL1-AS1 increased the number of cells in G1/S phase and decreased that of cells in G2 phase. RUVBL1-AS1 increased paclitaxel resistance and downregulate VCP expression. RUVBL1-AS1 affects cell cycle progression by downregulating VCP, resulting in the reduction of cells in G2/M phase, thereby weakening the sensitivity to paclitaxel.
Conclusion: The nomogram could accurately predict shrinkage modes after NAT, and may help guide the individualized selection of breast conserving surgery candidates after NAT. RUVBL1-AS1 might be a promising therapeutic target of paclitaxel-based chemotherapy inHER2 + breast cancer.
期刊介绍：
The International Journal of Surgery (IJS) has a broad scope, encompassing all surgical specialties. Its primary objective is to facilitate the exchange of crucial ideas and lines of thought between and across these specialties.By doing so, the journal aims to counter the growing trend of increasing sub-specialization, which can result in "tunnel-vision" and the isolation of significant surgical advancements within specific specialties.
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