新辅助化疗前后三阴性乳腺癌肿瘤的基因组和转录组分析。

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2024-10-07 DOI:10.1111/cas.16339
Tomomi Nishimura, Ravi Velaga, Norikazu Masuda, Kosuke Kawaguchi, Shuji Kawaguchi, Masahiro Takada, Yurina Maeshima, Sunao Tanaka, Yuichiro Kikawa, Takayuki Kadoya, Hiroko Bando, Rikiya Nakamura, Yutaka Yamamoto, Takayuki Ueno, Hiroyuki Yasojima, Hiroshi Ishiguro, Satoshi Morita, Shinji Ohno, Hironori Haga, Fumihiko Matsuda, Seishi Ogawa, Masakazu Toi
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引用次数: 0

摘要

我们对使用微管抑制剂(MTIs)对三阴性乳腺癌(TNBC)进行新辅助治疗的了解仍然有限。为了进一步了解乳腺癌驱动基因的突变状态对病理完全反应(pCR;ypT0/isypN0)预测的作用,并确定艾瑞布林和紫杉醇等MTIs的不同基因集,我们对日本乳腺癌研究小组22(JBCRG-22)临床试验中的TNBC肿瘤样本进行了靶向基因组(n = 50)和全转录组分析(n = 64)。同源重组缺陷(HRD)高(HRD评分≥42分)肿瘤的PIK3CA、PTEN和HRAS突变率较低,pCR率较高。当根据肿瘤 BRCA 突变状态对 HRD 高肿瘤进行分层时,BRCA2 突变肿瘤的 pCR 率更高(83% 对 36%)。TP53阳性肿瘤的转录组分析发现了FGFR2的下调(假发现率p值=2.07e-7),这也是分别接受紫杉醇和艾瑞布林联合卡铂治疗的pCR/准pCR的HRD-高和-低肿瘤之间唯一的共同基因。对HRD-高组治疗后肿瘤的差异富集分析表明,糖降解途径与HRD-高组有显著相关性(p = 0.006)。FGFR2的表达和差异富集通路在TNBC患者对含卡铂的MTIs治疗的反应和耐药性中起着作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors.

Our understanding of neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) remains limited. To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Lower PIK3CA, PTEN, and HRAS mutations were found in homologous recombination deficiency (HRD)-high (HRD score ≥ 42) tumors with higher pCR rates. When HRD-high tumors were stratified by tumor BRCA mutation status, the pCR rates in BRCA2-mutated tumors were higher (83% vs. 36%). Transcriptomic profiling of TP53-positive tumors identified downregulation of FGFR2 (false discovery rate p value = 2.07e-7), which was also the only common gene between HRD-high and -low tumors with pCR/quasi-pCR treated with paclitaxel and eribulin combined with carboplatin, respectively. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.

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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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