In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. LB-165-LB-165
Abstract:
Breast cancer incidence rates, clinical features, and risk factors are known to vary significantly by race/ethnicity. Recently, tumor sequencing and profiling analyses have improved molecular classification and refined existing breast cancer subtypes. However, detailed genomic analyses are limited in Asian populations. The goal of this study was to profile fresh frozen breast tumors and paired normal tissue in breast cancer cases who had surgeries at two hospitals in Hong Kong. Only tumors containing 50% or more tumor cells were included for sequencing. RNA sequencing (RNASeq), whole exome sequencing, and SNP array were conducted in ~100 tumors. In 92 tumors with RNASeq data, the unsupervised clustering analysis based on 2000 most variable genes identified two subgroups in patients with luminal tumors (defined by PAM50). The most significantly differentially expressed genes between the two luminal subgroups were enriched in immune and inflammation pathways. We further conducted the clustering analysis within 72 luminal tumors (luminal A + luminal B) using 700 immune genes, which again classified the patients into two subgroups (high-immune luminal [HILum] and low-immune luminal [LILum] ). Three computational algorithms, CIBERSORT, MCP-counter, and ESTIMATE, were used to infer the fraction or abundance of immune cell populations in each tumor using RNASeq data. We found significant differences in the abundance of most immune cell populations between the two luminal subgroups. The HILum group, which consisted of 53% of all luminal tumors, had a higher overall immune score as well as a higher score for each immune cell subpopulation measured by MCP-counter, at levels similar to those in patients with HER2-positive or basal-like tumors. HILum tumors also expressed significantly higher levels of immune checkpoint genes such as PD1, PDL1, and CTLA4 compared with LILum tumors. Interestingly, HILum was also associated with lower ESR1 expression, earlier age onset, higher level of ploidy and loss-of-heterozygosity, and higher proportions of APOBEC signatures (mutation signatures 2 and 13 in COSMIC) and lower occurrence of the defective DNA mismatch repair signature (signature 6) compared with LILum. The HILum subtype is not specific to Hong Kong since similar results were seen in both TCGA white and Asian breast cancer patients. In summary, we identified a group of luminal patients who had higher levels of immune cell infiltration and immune checkpoint gene expression and are associated with distinct genomic features. These patients may potentially benefit from the immune checkpoint inhibitor therapies. Citation Format: Xiaohong (Rose) Yang, Bin Zhu, Difei Wang, Hela Koka, Tongwu Zhang, Feng Wang, Cherry Wu, Koon Ho Tsang, Wing-cheong Chan, Sze Hong Law, Priscilla Lee, Mengjie Li, Wentao Li, Suyang Wu, Zhiguang Liu, Mingyi Wang, Kristine Jones, Amy Hutchinson, Belynda Hicks, Jianxin Shi, Shelly Lap Ah Tse. Identification of a luminal subtype with high immune abundance among breast cancer patients in Hong Kong, China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-165.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-LB-165
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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