一个预后免疫预测因子 HLA-DRA 在非肌肉浸润性和肌肉浸润性膀胱癌中发挥多种作用。
A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer.
机构信息
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea; Department of Urology, Chungbuk National University Hospital, Cheongju, South Korea.
出版信息
Urol Oncol. 2021 Apr;39(4):237.e21-237.e29. doi: 10.1016/j.urolonc.2020.11.017. Epub 2020 Dec 15.
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.
背景
人们对癌症预后免疫生物标志物的需求日益增长。各种癌症的免疫标志物的预后意义已经得到证实，但膀胱癌（BCa）的生物标志物尚未得到充分评估。为了阐明人类白细胞抗原 DR 链（HLA-DRA）在 BCa 发展中的作用，我们检测了非肌肉浸润性膀胱癌（NMIBC）和肌肉浸润性膀胱癌（MIBC）组织样本中 HLA-DRA mRNA 的表达。
材料和方法
使用 96 例 NMIBC、43 例 MIBC 和 59 例非癌性 BCa 周围组织的组织样本，通过实时聚合酶链反应检测 HLA-DRA 基因的表达。还测量了调节 HLA-DRA 的上游基因的表达，以解释 HLA-DRA 在 BCa 中的作用。
结果
高级别 NMIBC 患者的 HLA-DRA 表达高于低级别 NMIBC 患者（P < 0.05）。此外，进展为 MIBC 的 NMIBC 患者 HLA-DRA mRNA 表达较高。Kaplan-Meier 分析显示，HLA-DRA 低表达的 NMIBC 患者无进展生存期优于 HLA-DRA 高表达的患者（P=0.004）。此外，NMIBC 和 MIBC 中调节 HLA-DRA 的基因表达不同，表明 HLA-DRA 在两种癌症中的免疫调节作用不同。
结论
NMIBC 患者 HLA-DRA 的高表达对患者分层策略以及 BCa 肿瘤免疫学具有重要意义。
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