دورية أكاديمية
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Genetic and immune characteristics of sentinel lymph node metastases and multiple lymph node metastases compared to their matched primary breast tumours

التفاصيل البيبلوغرافية
العنوان: Genetic and immune characteristics of sentinel lymph node metastases and multiple lymph node metastases compared to their matched primary breast tumours
المؤلفون: Bo Chen, Guochun Zhang, Jianguo Lai, Weikai Xiao, Xuerui Li, Cheukfai Li, Hsiaopei Mok, Kai Li, Yulei Wang, Li Cao, Minghan Jia, Chongyang Ren, Lingzhu Wen, Guangnan Wei, Jiali Lin, Yingzi Li, Yuchen Zhang, Xiaoqing Chen, Xueying Wu, Henghui Zhang, Min Li, Jing Liu, Charles M. Balch, Ning Liao
المصدر: EBioMedicine, Vol 71, Iss , Pp 103542- (2021)
بيانات النشر: Elsevier, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Breast cancer, Sentinel lymph node metastases, Multiple lymph node metastases, Genome, Immune characteristics, Medicine, Medicine (General), R5-920
الوصف: Background: Patients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs). Methods: Genomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis. Findings: The downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis. Interpretation: Single lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node. Funding: This work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396421003352; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2021.103542
URL الوصول: https://doaj.org/article/bac98652b6cc4416b4f4555ae1723e32
رقم الأكسشن: edsdoj.bac98652b6cc4416b4f4555ae1723e32
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2021.103542