Oshi Masanori, Gandhi Shipra, Tokumaru Yoshihisa, Yan Li, Yamada Akimitsu, Matsuyama Ryusei, Ishikawa Takashi, Endo Itaru, Takabe Kazuaki
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center Buffalo, New York 14263, USA.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine Yokohama 236-0004, Japan.
Am J Cancer Res. 2021 Oct 15;11(10):5094-5110. eCollection 2021.
Epidermal growth factor receptor () is one of the receptors that belong to the epidermal growth factor family of receptor tyrosine kinases (ErbBs). Several malignancies including breast cancer that express EGFR have poor prognosis. Our study examined the EGFR expression among 5176 breast cancer patients from GSE96058 and METABRIC cohorts and the contribution of tumor immune microenvironment in different subtypes. We found that among different breast cancer subtypes, expression in TNBC was the highest compared to other subtypes. high ER-positive/HER2-negative breast cancer had significantly higher survival compared to low ER-positive/HER2-negative breast cancer. It was also associated with high level of intratumor heterogeneity and homologous recombination defects (HRD). This group was also enriched in immune-related gene sets. On the other hand, low tumor was enriched in cell proliferation-related gene sets. However, these findings were not observed in . Interestingly, there was a greater infiltration of anti-cancer immune cells in high ER-positive/HER2-negative breast cancers, while, TNBC with higher EGFR expression had lower fraction of immune cells along with low level of cytolytic activity. Tumor cells have significantly higher expression compared to immune cells in single cell sequencing data. There was higher expression of immune checkpoint molecules in high ER-positive/HER2-negative breast cancer but lower expression in TNBC. High metastatic tumor was significantly associated with worse survival, but no association with infiltrating immune cells was observed. Our study shows that higher expression in ER-positive/HER2-negative breast cancer is associated with improved outcomes and an anti-cancer immune microenvironment.
表皮生长因子受体（EGFR）是属于受体酪氨酸激酶（ErbBs）表皮生长因子家族的受体之一。包括乳腺癌在内的几种恶性肿瘤表达EGFR时预后较差。我们的研究检测了来自GSE96058和METABRIC队列的5176例乳腺癌患者的EGFR表达情况以及肿瘤免疫微环境在不同亚型中的作用。我们发现，在不同的乳腺癌亚型中，三阴乳腺癌（TNBC）中的EGFR表达与其他亚型相比是最高的。EGFR高表达的雌激素受体阳性/人表皮生长因子受体2阴性（ER阳性/HER2阴性）乳腺癌与EGFR低表达的ER阳性/HER2阴性乳腺癌相比，生存期显著更长。它还与高水平的肿瘤内异质性和同源重组缺陷（HRD）相关。这一组在免疫相关基因集中也有富集。另一方面，EGFR低表达的肿瘤在细胞增殖相关基因集中有富集。然而，在三阴乳腺癌中未观察到这些结果。有趣的是，EGFR高表达的ER阳性/HER2阴性乳腺癌中有更多的抗癌免疫细胞浸润，而EGFR表达较高的三阴乳腺癌免疫细胞比例较低且细胞溶解活性水平也低。在单细胞测序数据中，肿瘤细胞的EGFR表达明显高于免疫细胞。EGFR高表达的ER阳性/HER2阴性乳腺癌中免疫检查点分子的表达较高，但在三阴乳腺癌中表达较低。EGFR高表达的转移性肿瘤与较差的生存期显著相关，但未观察到与浸润免疫细胞的关联。我们的研究表明，ER阳性/HER2阴性乳腺癌中较高的EGFR表达与更好的预后和抗癌免疫微环境相关。
