Age-Related Clusters and Favorable Immune Phenotypes in Breast Cancer of the Young Patients

IF 7.1 1区 医学 Q1 PATHOLOGY
Lise Martine Ingebriktsen , Amalie Abrahamsen Svanøe , Anna Kristine Myrmel Sæle , Rasmus Olai Collett Humlevik , Karen Toska , May Britt Kalvenes , Turid Aas , Anette Heie , Cecilie Askeland , Gøril Knutsvik , Ingunn Marie Stefansson , Lars Andreas Akslen , Erling Andre Hoivik , Elisabeth Wik
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引用次数: 0

Abstract

Breast cancer (BC) patients aged <40 years at diagnosis experience aggressive disease and poorer survival compared with women diagnosed with BC at 40 to 49 years, but the age-related biology is described to little extent. Here, we explored transcriptional alterations in BC to gain better understanding of age-related tumor biology. We studied a subset of the Bergen in-house cohort (n = 127; age range, 26-49 years) and used the NanoString Breast Cancer 360 expression panel on formalin-fixed paraffin-embedded BC tissue, and publicly available global BC messenger RNA expression data (n = 204, age range, 22-49 years), to explore differentially expressed genes between the young (age <40 years) and older (age 40-49 years) patients. Unsupervised hierarchical clustering was applied to identify gene expression–based patient clusters. We applied established computational approaches to define the PAM50 subtypes, risk of recurrence scores (ROR), and risk groups and to infer the proportions of 22 immune cell types from bulk gene expression profiles of patients aged <50 years at BC diagnosis. Differentially expressed genes and gene sets were investigated using OncoEnrichR and g:Profiler to describe functional profiles and pathway enrichment. We identified 4 age-related patient clusters presenting distinct characteristics of PAM50 subtypes and ROR profiles, which demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the known molecular subtypes. Our findings showed better survival than expected in the basal-enriched cluster 2 and in triple-negative and basal-like BC. Deconvolution analyses of immunophenotypes indicated higher levels of M0 and M1 macrophages than M2 macrophages in subsets of young BC. Our approach identifies age-based patient clusters with distinct clinicopathologic profiles, to a large extent overlapping with the PAM50 subtypes, although with independent prognostic values in multivariate survival analyses. The patient clusters provided new insight in the immune cell distribution across tumor subtypes, potentially contributing to survival differences between the clusters and the molecular subtypes and indicating age-related mechanisms improving outcome. Our study confirms the applicability of ROR as a valid prognosticator also in a young BC cohort.

年轻人乳腺癌中与年龄相关的群集和有利的免疫表型。
与 40-49 岁确诊的女性相比,40 岁以下确诊的乳腺癌(BC)患者病情凶险,生存率较低,但与年龄相关的生物学描述却很少。在此,我们探讨了乳腺癌的转录改变,以更好地了解与年龄相关的肿瘤生物学。我们研究了卑尔根内部队列的一个子集(n=127,年龄范围为 26-49),并使用 NanoString Breast Cancer 360 表达面板对福尔马林固定石蜡包埋的乳腺癌组织和公开可用的全球乳腺癌 mRNA 表达数据(n=204,年龄范围为 22-49)进行分析,以探索年轻女性(年龄为 25-49 岁)和 40-49 岁女性(年龄为 25-49 岁)之间的差异表达基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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