Research Paper|Volume 12, Issue 19|pp 19335—19351

TILRR (FREM1 isoform 2) is a prognostic biomarker correlated with immune infiltration in breast cancer

Xiao-Yi Xu^1,⁷, Wen-Jing Guo¹, Shi-Hua Pan¹, Ying Zhang^1,³, Feng-Lin Gao^1,³, Jiang-Tao Wang⁶, Sheng Zhang^1,³, He-Ying Li¹, Ren Wang^5,⁷, Xiao Zhang^1,^2,^3,⁴

¹CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, and Guangzhou Medical University, Guangzhou, Guangdong, China
²Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510530, Guangdong, China
³Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, Guangdong, China
⁴Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, Guangdong, Guangdong, China
⁵Affiliated Cancer Hospital and Institute, Guangzhou Medical University, Guangzhou 511436, Guangdong, China
⁶Department of Pathology, First People Hospital, Changde 415003, Hunan, China
⁷State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China

* Equal contribution

Received: January 24, 2020Accepted: July 7, 2020Published: October 8, 2020

https://doi.org/10.18632/aging.103798

Copyright: © 2020 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In atherosclerosis, upregulated TILRR (FREM1 isoform 2) expression increases immune cell infiltration. We hypothesized that TILRR expression is also correlated with cancer progression. By analyzing data from Oncomine and the Tumor Immune Estimation Resource, we found that TILRR mRNA expression was significantly lower in breast cancer tissue than adjacent normal tissue. Kaplan-Meier survival analysis and immunohistochemical staining revealed shortened overall survival and disease-free survival in patients with low TILRR expression. TILRR transcript expression was positively correlated with immune score, immune cell biomarkers and the expression of CXCL10 and CXCL11. TILRR expression was also positively correlated with CD8+ and CD4+ T-cell infiltration. These correlations were verified using the ESTIMATE algorithm, gene set enrichment analysis and Q-PCR. We concluded that impaired TILRR expression is correlated with breast cancer prognosis and immune cell infiltration.