[1]潘大庆,邱 成,张乐希,等.膀胱癌组织中HLA-I和PD-L1表达水平与临床病理学特征及细胞免疫浸润的相关性研究[J].现代检验医学杂志,2025,40(03):1-5,17.[doi:10.3969/j.issn.1671-7414.2025.03.001]
　PAN Daqing,QIU Cheng,ZHANG Lexi,et al.Correlation between HLA-I and PD-L1 Expression Levels and Clinicopathological Features and Cellular Immune Infiltration in Bladder Cancer[J].Journal of Modern Laboratory Medicine,2025,40(03):1-5,17.[doi:10.3969/j.issn.1671-7414.2025.03.001]
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膀胱癌组织中HLA-I和PD-L1表达水平与临床病理学特征及细胞免疫浸润的相关性研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年03期
页码:
1-5,17
栏目:
论著
出版日期:
2025-05-15

文章信息/Info

Title:
Correlation between HLA-I and PD-L1 Expression Levels and Clinicopathological Features and Cellular Immune Infiltration in Bladder Cancer
文章编号:
1671-7414（2025）03-001-06
作者:
潘大庆1，邱 成1，张乐希1，叶剑锋1，吴明青2
（1.中国科学技术大学附属第一医院/安徽省立医院器官移植一病区，合肥 230001；2．安徽医科大学生命科学学院，合肥 230032）
Author(s):
PAN Daqing1,QIU Cheng1,ZHANG Lexi1,YE Jianfeng1,WU Mingqing2
(1.Organ Transplantation Center, the First Affiliated Hospital of University of Science and Technology of China/Anhui Provincial Hospital, Hefei 230001,China;2.College of Life Sciences, Anhui Medical University, Hefei 230032,China)
关键词:
人类白细胞抗原I类分子; 程序性死亡配体1; 膀胱癌; 免疫功能
分类号:
R737.14；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.03.001
文献标志码:
A
摘要:
目的探讨人类白细胞抗原I类分子（HLA-I）和程序性死亡配体1（PD-L1）表达与临床病理学特征及细胞免疫浸润的相关性研究。方法回顾性选取2020年5月~2023年4月安徽省立医院诊治的150例膀胱癌患者作为研究对象，比较癌组织与癌旁组织HLA-I，PD-L1阳性表达率及阳性评分；比较不同临床特征膀胱癌患者癌组织HLA-I，PD-L1阳性评分，采用Kendall’stau-b法分析HLA-I，PD-L1与膀胱癌患者临床特征的相关性；采用Logistic回归模型建立HLA-I，PD-L1阳性评分联合模型参数，并绘制受试者工作特征（ROC）曲线分析HLA-I，PD-L1阳性评分及两项联合诊断膀胱癌的曲线下面积(AUC)，敏感度及特异度。结果癌组织的HLA-I阳性表达率低于癌旁组织[38.67%(58/150)vs81.33%(122/150)]，而PD-L1阳性表达率高于癌旁组织[57.33%(86/150)vs14.00%(21/150)]，差异具有统计学意义（χ2=56.889，61.377，均P<0.05）。癌组织的HLA-I阳性评分低于癌旁组织[2.00(1.00，3.00)vs3.00(3.00，5.00)]，而PD-L1阳性评分高于癌旁组织[3.00(2.00，5.00)vs2.00(1.00，2.00)]，差异具有统计学意义（Z=-8.409，-6.346，均P<0.05）。不同性别、年龄、肿瘤直径的HLA-I，PD-L1阳性评分比较，差异无统计学意义（ZHLA-1=-1.834,-0.622,-0.543,ZPD-L1=0.811，0.812，0.919，均P＞0.05）；不同病理分期、淋巴结转移、分化程度、CD4+，CD8+，CD68+的HLA-I，PD-L1阳性评分比较，差异具有统计学意义（ZHLA-1=-7.034~3.814，ZPD-L1=-4.479~3.257，均P＜0.05）。Kendall’stau-b相关性分析显示，HLA-I与病理分期、淋巴结转移、分化程度呈负相关，与CD4+，CD8+，CD68+浸润阴性呈正相关（r=-0.528~0.256，均P＜0.05），PD-L1与病理分期、淋巴结转移、分化程度呈正相关，与CD4+，CD8+，CD68+浸润阴性呈负相关（r=-0.243~0.334，均P＜0.05）。ROC曲线分析显示，HLA-I，PD-L1阳性评分及两项联合诊断膀胱癌的AUC值分别为0.773,0.702,0.856；敏感度分别为61.30%，57.30%，82.00%；特异度分别为81.30%，86.00%，73.30%。结论HLA-I，PD-L1在膀胱癌患者中呈异常表达趋势，且其表达可能会抑制机体免疫反应，分析HLA-I，PD-L1阳性表达情况有利于为临床诊治提供指导。
Abstract:
Objective To investigate the correlation between the expression of human leukocyte antigen class I (HLA-I) and programmed cell death ligand 1 (PD-L1) with clinicopathological features and cellular immune infiltration. Methods A total of 150 patients with bladder cancer diagnosed and treated in Anhui Provincial Hospital from May 2020 to April 2023 were retrospectively selected as the study objects. The positive expression rates and positive scores of HLA-I and PD-L1 were compared between cancerous tissues and adjacent tissues. The positive scores of HLA-I and PD-L1 in cancer tissues of patients with different clinical characteristics were compared, and the correlation between HLA-I, PD-L1 and clinical characteristics of patients with bladder cancer was analyzed by Kendall’s tau-b method. Logistic regression model was used to establish the combined model parameters of HLA-I and PD-L1 positive scores, and receiver operating characteristic (ROC) curve was drawn to analyze the HLA-I and PD-L1 positive scores and the area under the curve(AUC), sensitivity and specificity of the combined diagnosis of bladder cancer. Results The positive expression rate of HLA-I in cancer tissues was lower than that in paracancer tissues[38.67%(58/150) vs 81.33%(122/150)], while the positive expression rate of PD-L1 was higher than that in paracancer tissues [57.33%(86/150) vs 14.00%(21/150)], and the differences were statistically siginficant (χ2=56.889,61.377, all P<0.05). The HLA-I positive score of cancer tissues was lower than that of paracancer tissues[2.00(1.00,3.00) vs 3.00(3.00,5.00)], while the PD-L1 positive score was higher than that of paracancer tissues[3.00(2.00,5.00) vs 2.00(1.00,2.00)],and the fifferences were statistically significant (Z=-8.409,-6.346, all P<0.05). There was no significant difference in HLA-I and PD-L1 positive scores among different sex, age and tumor diameter (ZHLA-1=-1.834,-0.622,-0.543; ZPD-L1=0.811, 0.812, 0.919, all P ＞ 0.05). The difference of HLA-I and PD-L1 positive scores among different pathological stages, lymph node metastasis, differentiation degree, CD4+, CD8+ and CD68+ were statistically significant（ZHLA-1=-7.034~3.814; ZPD-L1=-4.479~3.257, all P ＜ 0.05). Kendall’s tau-b correlation analysis showed that HLA-I was negatively correlated with pathological stage, lymph node metastasis, degree of differentiation, and positively correlated with negative infiltration of CD4+, CD8+ and CD68+ (r=-0.528~-0.286, all P<0.05). PD-L1 was positively correlated with pathological stage, lymph node metastasis, degree of differentiation and negatively correlated with negative infiltration of CD4+, CD8+ and CD68+ (r=-0.243~0.334, all P<0.05). ROC curve analysis showed that the positive scores of HLA-I and PD-L1 and the AUC values of the combined diagnosis of bladder cancer were 0.773, 0.702 and 0.856, respectively. Sensitivity was 61.30%, 57.30% and 82.00%. The specificity was 81.30%, 86.00% and 73.30%. Conclusion The expression of HLA-I and PD-L1 is abnormal in patients with bladder cancer, and their expression is affected by the positive infiltration of immune cells. Observing the positive expression of HLA-I and PD-L1 is beneficial to provide guidance for clinical diagnosis and treatment.

参考文献/References:

[1] 杨金辉,郝彤彤,杨凌博,等.下调lncRNA CTC-425F1.4靶向调控miR-146a-3p表达对膀胱癌细胞的增殖和侵袭的影响[J].医学研究杂志,2022,51(2):62-66. YANG Jinhui, HAO Tongtong, YANG Lingbo, et al. Effect of down-regulating lncRNA CTC-425F1.4 on the proliferation and invasion of bladder cancer cells through targeted regulation of miR-146a-3p expression[J]. Journal of Medical Research, 2022, 51(2): 62-66.
[2] 袁琛,张晓玲,黄耿,等.miR-769-3p在膀胱癌组织中的表达及下调其表达对膀胱癌J82细胞迁移和细胞周期的影响[J].国际外科学杂志,2022,49(10):658-662, I0008. YUAN Chen, ZHANG Xiaoling, HUANG Geng, et al. Expression of miR-769-3p in bladder cancer tissues and the effect of its down-regulation on the migration and cell cycle of bladder cancer J82 cells[J]. International Journal of Surgery, 2022, 49(10): 658-662, I0008.
[3] 李俊朋,乔庆东,张琳,等.miR-34a与PD-1, PD-L1在膀胱癌中的临床意义[J].检验医学与临床,2023,20(8):1147-1149. LI Junpeng, QIAO Qingdong, ZHANG Lin, et al. The clinical significance of miR-34a,PD-1 and PD-L1 in bladder cancer[J]. Laboratory Medicine and Clinic, 2023, 20(8): 1147-1149.
[4] 白钰明,张国文,马可为,等.浸润性膀胱癌分子分型的预后研究及PD-L1的表达意义[J].临床泌尿外科杂志,2022,37(3):184-188. BAI Yuming, ZHANG Guowen, MA Kewei, et al. Prognostic analysis of molecular subtypes of invasive bladder cancer and PD-L1 as a potential prognostic marker[J]. Journal of Clinical Urology, 2022, 37(3): 184-188.
[5] 牟东云,张艳金,蒋立人,等.p-STAT3，PD-L1在膀胱尿路上皮癌中的表达及与临床病理特征的关系[J]. 重庆医学,2023,52(9):1330-1333. MU Dongyun, ZHANG Yanjin, JIANG Liren, et al. Expression of p-STAT3 and PD-L1 in urothelial carcinoma of bladder and their relationship with clinicopathological characteristics[J]. Chongqing Medicine, 2023, 52(9): 1330-1333.
[6] 国家癌症中心,国家肿瘤质控中心膀胱癌质控专家委员会.中国膀胱癌规范诊疗质量控制指标(2022版)[J].中华肿瘤杂志,2022,44(10):1003-1010.National Cancer Center，Bladder Cancer Expert Committee of National Cancer Quality Control Center. Quality control index for standardized diagnosis and treatment of bladder cancer in China(2022 edition)[J]. Chinese Journal of Oncology, 2022, 44(10): 1003-1010.
[7] 秦建文,张楠,刘小林,等.膀胱癌患者癌组织Fibulin-3，SENP1，NCOA1表达与疾病进展及复发的关系[J].川北医学院学报,2022,37(2):197-201. QIN Jianwen, ZHANG Nan, LIU Xiaolin, et al. Relationship of Fibulin-3,SENP1 and NCOA1 expression in bladder cancer tissues with disease progression and recurrence[J]. Journal of North Sichuan Medical College, 2022, 37(2): 197-201.
[8] KOBAYASHI M, FUJIYAMA N, TANEGASHIMA T, et al. Effect of HLA genotype on intravesical recurrence after bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer[J]. Cancer Immunology, Immunotherapy, 2022, 71(3): 727-736.
[9] 王欢,韦良军,潘宏鑫,等.程序性细胞死亡受体-1抑制剂联合化疗新辅助治疗肌层浸润性膀胱癌的应用研究[J].哈尔滨医科大学学报,2022,56(4):341-345. WANG Huan, WEI Liangjun, PAN Hongxin, et al. Application of programmed death 1 inhibitors combined neoadjuvant chemotherapy in the treatment of muscle-invasive bladder cancer[J]. Journal of Harbin Medical University, 2022, 56(4): 341-345.
[10] SRIDHAR S S, POWLES T, CLIMENT DUR?N M ?, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: analysis from JAVELIN bladder 100 by duration of first-line chemotherapy and interval before maintenance[J]. European Urology, 2024, 85(2): 154-163.
[11] 李绪鲲,刘星,唐义权.膀胱癌患者血清CK-19， CYFRA21-1的表达及其临床意义[J].中国现代医学杂志,2021,31(22):17-21. LI Xukun, LIU Xing, TANG Yiquan. The expression and clinical significance of CK-19 and CYFRA21-1 in serum of patients with bladder cancer[J]. China Journal of Modern Medicine, 2021, 31(22): 17-21.
[12] SUN Lin, MU Luwen, ZHOU Jing, et al. Imaging features of gadoxetic acid-enhanced MR imaging for evaluation of tumor-infiltrating CD8 cells and PD-L1 expression in hepatocellular carcinoma[J]. Cancer Immunology, Immunotherapy, 2022, 71(1): 25-38.
[13] YAMASHITA S, ABE H, YAMASHITA H, et al. PD-L1 and HLA-class I expression status and their therapeutic implication in oesophageal small-cell carcinoma[J]. Histopathology, 2023, 83(2): 264-275.
[14] 景琼,吴金平,王光亚.miR-34a,PD-1,PD-L1在膀胱癌中的表达及其与预后的相关性分析[J].医学综述, 2019,25(20):4133-4138. JING Qiong, WU Jinping, WANG Guangya. Expression of miR-34a, PD-1, PD-L1 in bladder cancer and their correlation with prognosis[J]. Medical Recapitulate, 2019, 25(20): 4133-4138.
[15] 邱忠凯,刘俊龙,丁全明,等.膀胱癌患者血清中肿瘤异常蛋白和细胞角蛋白19的表达及其临床意义[J].中国医科大学学报,2023,52(7):628-632.
QIU Zhongkai, LIU Junlong, DING Quanming, et al. Expression and clinical significance of tumor abnormal protein and cytokeratin 19 in the serum of patients with bladder cancer[J]. Journal of China Medical University, 2023, 52(7): 628-632.
[16] 邢俊杰,盛永亮,张浩然,等.非肌层浸润性膀胱癌TURBT治疗患者血清UBC1和DJ-1表达水平及其对预后预测价值研究[J].现代检验医学杂志, 2023,38(3):29-34. XING Junjie, SHENG Yongliang, ZHANG Haoran, et al. Study on serum UBC1,DJ-1 expression levels and their prognostic value in patients with Non muscular invasive bladder cancer treated with TURBT[J]. Journal of Modern Laboratory Medicine, 2023, 38(3): 29-34.
[17] 张庆磊,满其荣,李平,等.肿瘤微环境中CD4+T细胞浸润、MFAP5与膀胱癌患者预后关系的临床研究[J].中国免疫学杂志,2023,39(8):1719-1723. ZHANG Qinglei, MAN Qirong, LI Ping, et al. Clinical study of relationship between CD4+T lymphocyte infiltration,MFAP5 and prognosis in bladder cancer patients[J]. Chinese Journal of Immunology, 2023, 39(8): 1719-1723.
[18] 何秀萍,邢益涛,颜建,等.扶正祛瘀解毒方联合表柔比星灌注化疗对老年非肌层浸润性膀胱癌术后复发的影响[J].中国老年学杂志,2023,43(20):4922-4925. HE Xiuping, XING Yitao, YAN Jian, et al. Effect of Fuzheng Quyu jiedu prescription combined with epirubicin infusion chemotherapy on postoperative recurrence of non-muscular invasive bladder cancer in elderly patients[J]. Chinese Journal of Gerontology, 2023, 43(20): 4922-4925.

备注/Memo

备注/Memo:
基金项目：国家自然基金项目（82003000）。
作者简介：潘大庆（1992-），男，硕士，医师，研究方向：外科学（泌尿外科学），E-mail:dfong 321@126.com。
通讯作者：吴明青（1993-），女，硕士，助理实验师，研究方向：肿瘤表观遗传，E-mail:wumingqing@163.com。
更新日期/Last Update: 2025-05-15