Role of human leukocyte antigenDR expression on predicting the prognosis of hepatocellular carcinoma

doi:10.3760/cma.j.issn.1673-422X.2018.03.009

Abstract

Abstract: Objective To explore the expression of human leukocyte antigen DR (HLA-DR) in hepatocellular carcinoma and its clinical values in predicting prognosis. Methods The primary hepatocellular carcinoma tissues of 97 patients in our hospital from August 2012 to February 2014 were enrolled as subjects (case group), and the adjacent normal liver tissues were selected as control (control group, n=97). The expressions of HLADR in the two groups were detected by immunohistochemistry, and the relationships between HLADR expression and clinicopathological features, recurrence and prognosis were analyzed. Results The positive expression rate of HLADR in specimens of case group was 55.67%, which was higher than 21.65% in control group, and the difference was statistically significant (χ2=23.671, P<0.001). The positive expression rates of HLADR in tumor tissues with diameter ≥4cm, Ⅲ-Ⅳ stage, poorly differentiated, bile duct cell carcinoma, no lymph node metastasis were higher than those in tumor tissues with diameter <4cm, Ⅰ-Ⅱ stage, medium and well differentiated, hepatocellular carcinoma, lymph node metastasis respectively, and the differences were statistically significant (χ2=10.481, P=0.001; χ2=18.854, P<0.001; χ2=9.876, P=0.002; χ2=6.834, P=0.009; χ2=30.668，P<0.001). The recurrence rates of 2 years and 3 years were 27.91% and 46.51% in patients with negative expression of HLADR respectively, which were lower than 50.00% and 70.37% in patients with positive expression of HLADR respectively, and the differences were statistically significant (χ2=4.860, P=0.028; χ2=5.668, P=0.017). The median survival time of patients with HLADR positive expression was 33.64 months, which was shorter than 36.88 months in patients with negative expression, and the difference was statistically significant (χ2=10.356, P＜0.001). TNM staging Ⅲ-Ⅳ (OR=0.899, 95%CI: 0.721-0.995, P=0.012) and positive expression of HLADR (OR=1.125, 95%CI: 1.025-2.568, P=0.018) were unfavorable to the prognosis of hepatocellular carcinoma patients. Conclusion HLA-DR expresses abnormally in patients with primary hepatocellular carcinoma, which may be involved in the occurrence and development of hepatocellular carcinoma, and the upregulation of HLA-DR in patients with hepatocellular carcinoma indicates a high recurrence rate and short survival time.

Key words: HLA-DR antigens, Liver neoplasms, Prognosis, Pathological features

Wu Quanlin, He Yaopeng. Role of human leukocyte antigenDR expression on predicting the prognosis of hepatocellular carcinoma[J]. Journal of International Oncology, 2018, 45(3): 166-171.

References

［1］ Niwa Y, Matsuura H, Murakami M, et al. Evidence that naturopathic therapy including cordyceps sinensis prolongs survival of patients with hepatocellular carcinoma［J］. Integr Cancer Ther, 2013, 12(1): 50-68. DOI: 10.1177/1534735412441704. ［2］冯超, 赵剑波, 陈勇, 等. 原发性肝癌切除术后预防性经肝动脉介入治疗：肝动脉化疗栓塞术和化疗灌注术比较［J］. 介入放射学杂志, 2014, 23(8): 679-682. DOI: 10.3969/j.issn.1008-794X.2014.07.09. ［3］ Wu WR, Zhang R, Shi XD, et al. Notch1 is overexpressed in human intrahepatic cholangiocarcinoma and is associated with its proliferation, invasiveness and sensitivity to 5fluorouracil in vitro［J］. Oncol Rep, 2014, 31(6): 2515-2524. DOI: 10.3892/or.2014.3123. ［4］ BrignoleBaudouin F, Riancho L, Ismail D, et al. Correlation between the inflammatory marker HLADR and signs and symptoms in moderate to severe dry eye disease［J］. Invest Ophthalmol Vis Sci, 2017, 58(4): 2438-2448. DOI: 10.1167/iovs.15-16555. ［5］ Wen J, Xie K, Zhang M, et al. HLADR, and not PLA2R, is expressed on the podocytes in kidney allografts in de novo membranous nephropathy［J］. Medicine (Baltimore), 2016, 95(37): e4809. DOI: 10.1097/MD.0000000000004809. ［6］ Jia J, Li H, Wang H, et al. Hepatitis B virus core antigen mutations predict postoperative prognosis of patients with primaryhepatocellular carcinoma［J］. J Gen Virol, 2017, 98(6): 1399-1409. DOI: 10.1099/jgv.0.000790. ［7］ He S, Wei H, Ma Y, et al. Outcomes of metastatic spinal cord compression secondary to primary hepatocellular carcinomawith multidisciplinary treatments［J］. Oncotarget, 2017, 8(26): 43439-43449. DOI: 10.18632/oncotarget.15708. ［8］ Ohata T, Yokoo H, Kamiyama T, et al. Fatty acidbinding protein 5 function in hepatocellular carcinoma through induction of epithelialmesenchymal transition［J］. Cancer Med, 2017, 6(5): 10491061. DOI: 10.1002/cam4.1020. ［9］ Tang J, Chen JX, Chen L, et al. Metastasis associated in colon cancer 1 (MACC1) promotes growth and metastasis processes of colon cancer cells［J］. Eur Rev Med Pharmacol Sci, 2016, 20(13): 2825-2834. ［10］崔冉亮, 李悦国, 张鹏宇, 等. 血清高尔基体蛋白73联合甲胎蛋白检测在原发性肝癌患者中的诊断价值［J］. 中国肿瘤临床, 2015, 42(4): 222-225. DOI: 10.3969/j.issn.1000-8179.20140757. ［11］ Yao S, Zhang J, Chen H, et al. Diagnostic value of immunohistochemical staining of GP73, GPC3, DCP, CD34, CD31, and reticulin staining in hepatocellular carcinoma［J］. J Histochem Cytochem, 2013, 61(9): 639-648. DOI: 10.1369/0022155413492771. ［12］ Yang Y, Liu Q, Zhang H, et al. Silencing of GP73 inhibits invasion and metastasis via suppression of epithelialmesenchymal transition in hepatocellular carcinoma［J］. Oncol Rep, 2017, 37(2): 1182-1188. DOI: 10.3892/or.2017.5351. ［13］ Radojevic K, Rakin A, Pilipovic I, et al. Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment［J］. J Neuroimmunol, 2014, 272(1/2): 16-28. DOI: 10.1016/j.jneuroim.2014.04.010. ［14］ Dunne MR, Michielsen AJ, O′Sullivan KE, et al. HLADR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients［J］. Cancer Immunol Immunother, 2017, 66(7): 841-850. DOI: 10.1007/s00262-017-1983-1. ［15］ Santos AM, Pena P, Avila M, et al. Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis［J］. Clin Rheumatol, 2017, 36(4): 953-958. DOI: 10.1007/s1006701635162. ［16］ Wogsland CE, Greenplate AR, Kolstad A, et al. Mass cytometry of follicular lymphoma tumors reveals intrinsic heterogeneity in proteins including HLADR and a deficit in nonmalignant plasmablast and germinal center Bcell populations［J］. Cytometry B Clin Cytom, 2017, 92(1): 79-87. DOI: 10.1002/cyto.b.21498. ［17］ Wahab MA, El Hanafy E, El Nakeeb A, et al. Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma (experience with 22 patients over a 15year period)［J］. World J Gastrointest Surg, 2017, 9(2): 61-67. DOI: 10.4240/wjgs.v9.i2.61.

[1]	Qian Xiaotao, Shi Ziyi, Hu Ge, Wu Xiaowei. Efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma： a real-world clinical study [J]. Journal of International Oncology, 2024, 51(6): 326-331.
[2]	Yang Mi, Bie Jun, Zhang Jiayong, Deng Jiaxiu, Tang Zuge, Lu Jun. Analysis of the efficacy and prognosis of neoadjuvant therapy for locally advanced resectable esophageal cancer [J]. Journal of International Oncology, 2024, 51(6): 332-337.
[3]	Chen Hongjian, Zhang Suqing. Study on the relationship between serum miR-24-3p， H2AFX and clinical pathological features and postoperative recurrence in liver cancer patients [J]. Journal of International Oncology, 2024, 51(6): 344-349.
[4]	Fan Zhipeng, Yu Jing, Hu Jing, Liao Zhengkai, Xu Yu, Ouyang Wen, Xie Conghua. Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy [J]. Journal of International Oncology, 2024, 51(5): 257-266.
[5]	Yang Lin, Lu Ning, Wen Hua, Zhang Mingxin, Zhu Lin. Study on the clinical relationship between inflammatory burden index and gastric cancer [J]. Journal of International Oncology, 2024, 51(5): 274-279.
[6]	Liu Pingping, He Xuefang, Zhang Yi, Yang Xu, Zhang Shanshan, Ji Yifei. Risk factors of postoperative recurrence in patients with primary brain glioma and prediction model construction [J]. Journal of International Oncology, 2024, 51(4): 193-197.
[7]	Wan Fang, Yang Gang, Li Rui, Wan Qijing. Expression levels and clinical significance of serum miR-497 and miR-383 in patients with esophageal cancer [J]. Journal of International Oncology, 2024, 51(4): 204-209.
[8]	Yao Yixin, Shen Yulin. Predictive value of serum SOCS3 and TXNIP levels for the prognosis of patients with hepatocellular carcinoma treated with TACE [J]. Journal of International Oncology, 2024, 51(4): 217-222.
[9]	Sun Weiwei, Yao Xuemin, Wang Pengjian, Wang Jing, Jia Jinghao. Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes [J]. Journal of International Oncology, 2024, 51(3): 143-150.
[10]	Liu Yulan, Jing Haiyan, Sun Jing, Song Wei, Sha Dan. Advances in predicting efficacy and prognostic markers of immunotherapy for gastric cancer [J]. Journal of International Oncology, 2024, 51(3): 175-180.
[11]	Peng Qin, Cai Yuting, Wang Wei. Advances on KPNA2 in liver cancer [J]. Journal of International Oncology, 2024, 51(3): 181-185.
[12]	Sun Guobao, Yang Qian, Zhuang Qingchun, Gao Binbin, Sun Xiaogang, Song Wei, Sha Dan. Research progress on the histopathological growth patterns of colorectal liver metastasis [J]. Journal of International Oncology, 2024, 51(2): 114-118.
[13]	Chen Boguang, Wang Sugui, Zhang Yongjie. Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer [J]. Journal of International Oncology, 2024, 51(2): 73-82.
[14]	Jin Xudong, Chen Zhongjian, Mao Weimin. Research progress on the role of MTAP in malignant mesothelioma [J]. Journal of International Oncology, 2024, 51(2): 99-104.
[15]	Huang Zhen, Chen Yongshun. Research progress of circulating tumor DNA in the diagnosis and treatment of hepatocellular carcinoma [J]. Journal of International Oncology, 2024, 51(1): 59-64.