A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

Xuan-Mei Piao; Ho Won Kang; Pildu Jeong; Young Joon Byun; Hee Youn Lee; Kyeong Kim; Sung Phil Seo; Won Tae Kim; Jong-Young Lee; Yun-Sok Ha; Yung Hyun Choi; Sung-Kwon Moon; Seok Joong Yun; Wun-Jae Kim

doi:10.1016/j.urolonc.2020.11.017

A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

Urol Oncol. 2021 Apr;39(4):237.e21-237.e29. doi: 10.1016/j.urolonc.2020.11.017. Epub 2020 Dec 15.

Authors

Affiliations

¹ Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
² Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea; Department of Urology, Chungbuk National University Hospital, Cheongju, South Korea.
³ Department of Urology, Chungbuk National University Hospital, Cheongju, South Korea.
⁴ Oneomics Institute, Seoul, South Korea.
⁵ Department of Urology, School of Medicine, Kyungpook National University, Daegu, South Korea; Department of Urology, Kyungpook National University Hospital, Daegu, South Korea.
⁶ Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, South Korea.
⁷ Department of Food Science and Technology, Chung-Ang University, Ansung, South Korea.
⁸ Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea; Department of Urology, Chungbuk National University Hospital, Cheongju, South Korea. Electronic address: sjyun@chungbuk.ac.kr.
⁹ Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea; Institute of Urotech, Cheongju, South Korea. Electronic address: wjkim@chungbuk.ac.kr.

PMID: 33339725
DOI: 10.1016/j.urolonc.2020.11.017

Abstract

Background: There is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).

Materials and methods: Tissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.

Results: Patients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.

Conclusions: High expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.

Keywords: HLA-DRA; Immune biomarker; Muscle invasive bladder cancer; Nonmuscle invasive bladder cancer; Prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor / genetics
Biomarkers, Tumor / immunology*
Female
Gene Expression Regulation, Neoplastic
HLA-DR alpha-Chains / genetics
HLA-DR alpha-Chains / immunology*
Humans
Male
Middle Aged
Neoplasm Invasiveness
Prognosis
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / immunology*
Urinary Bladder Neoplasms / pathology*

Substances

Biomarkers, Tumor
HLA-DR alpha-Chains