|本期目录/Table of Contents|

[1]张泽武,张伟.ARID1A表达与肝内胆管癌免疫细胞浸润及预后的相互关系研究[J].天津医科大学学报,2022,28(05):466-471.
 ZHANG Ze-wu,ZHANG Wei.Correlation of ARID1A expression with immune cell infiltration and prognosis of intrahepatic cholangiocarcinoma[J].Journal of Tianjin Medical University,2022,28(05):466-471.
点击复制

ARID1A表达与肝内胆管癌免疫细胞浸润及预后的相互关系研究(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
28卷
期数:
2022年05期
页码:
466-471
栏目:
肝胆疾病专题
出版日期:
2022-09-20

文章信息/Info

Title:
Correlation of ARID1A expression with immune cell infiltration and prognosis of intrahepatic cholangiocarcinoma
文章编号:
1006-8147(2022)05-0466-06
作者:
张泽武张伟
(天津医科大学肿瘤医院肝胆肿瘤科,国家肿瘤临床医学研究中心,天津市“肿瘤防治重点”实验室,天津市恶性肿瘤临床医学研究中心,天津300060)
Author(s):
ZHANG Ze-wuZHANG Wei
(Department of Hepatobiliary Cancer,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin;Tianjin′s Clinical Research Center for Cancer,Tianjin 300060,China)
关键词:
ARID1A肝内胆管癌免疫组化免疫细胞
Keywords:
ARID1Aintrahepatic cholangiocarcinomaimmunohistochemical stainingimmune cells
分类号:
R735.8
DOI:
-
文献标志码:
A
摘要:
目的:探讨ARID1A基因的表达与肝内胆管癌免疫细胞浸润的关系及预后分析。方法:纳入2011年1月—2017年12月天津医科大学肿瘤医院接受手术治疗的136例肝内胆管癌患者,收集患者的临床资料和病理组织标本,构建组织微阵列芯片,采用免疫组织化学染色方法检测ARID1A表达和不同类型的免疫细胞浸润程度。分析ARID1A基因的预后价值、临床特征和免疫细胞浸润的关系。通过在线数据库评估ARID1A拷贝数与多种肿瘤免疫细胞浸润关系。结果:136例肝内胆管癌患者中ARID1A在108例(79.4%)中表达,而在28例(20.6%)中表达缺失。与癌旁组织相比,CD4+、CD8+T淋巴细胞和CD163+巨噬细胞在肿瘤组织中浸润明显减少(t=6.962、7.364、7.905,均P<0.000 1),而CD66b+中性粒细胞在肿瘤组织浸润明显增加(t=4.093,P<0.000 1)。在ARID1A表达缺失组和ARID1A表达组中CD163+巨噬细胞的浸润水平与生存呈负相关(log-rank ?字2=5.399、6.376,P=0.02、0.012)。ARID1A的表达与肝硬化呈正相关( ?字2=7.126,P<0.01)。与ARID1A表达组相比,CD4+T淋巴细胞、CD8+T淋巴细胞和CD163+巨噬细胞在ARID1A表达缺失的肝内胆管癌中的浸润水平明显降低(t=2.174、1.998、2.162,均P<0.05)。通过TIMER在线数据库分析发现在乳腺癌basal-like型和低级胶质瘤中,ARID1A拷贝数缺失与多数免疫细胞浸润水平降低相关(P<0.05)。结论:在肝内胆管癌中,ARID1A表达缺失与肿瘤微环境中CD4+、CD8+T淋巴细胞和CD163+巨噬细胞浸润降低相关,而CD163+巨噬细胞的浸润与生存预后呈负相关。
Abstract:
Objective: To investigate the relationship between the expression of ARID1A and the infiltration of immune cells of intrahepatic cholangiocarcinoma,and the prognostic value. Methods: A total of 136 consecutive patients with intrahepatic cholangiocarcinoma who received surgical treatment at Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2017 were enrolled,and their clinicopathological information and pathological tissue specimens were collected. Tissue microarrays were constructed. The immunohistochemical staining method was used to detect the expression of ARID1A and the infiltration degree of different types of immune cells. The relationship between the prognostic value of ARID1A gene,clinical features and immune cell infiltration were analyzed. The relationship between ARID1A copy number and infiltration of various tumor immune cells through online database were also evaluated. Results: Among 136 patients with intrahepatic cholangiocarcinoma,the expression of ARID1A gene was present in 108 cases(79.4%),while absent in 28 cases(20.6%). Compared with adjacent normal tissue,the infiltration of CD4+,CD8+ T lymphocytes and CD163+ macrophages in tumor tissues were significantly reduced(t=6.962,7.364,7.905,all P<0.000 1),while the infiltration of CD66b+ neutrophils in tumor tissues was significantly increased(t=4.093,P<0.0001). In ARID1A expression loss group and ARID1A expression group,the infiltration level of CD163+macrophages was negatively correlated with survival(log-rank ?字2=5.399,6.376,P=0.02,0.012). The expression of ARID1A was positively correlated with liver cirrhosis( ?字2=7.126,P<0.01). Compared with the ARID1A expression group,the infiltration level of CD4+ T lymphocytes,CD8+ T lymphocytes and CD163+ macrophages in the ARID1A expression loss group were significantly reduced(t=2.174,1.998,2.162,all P<0.05). Through the analysis of TIMER online database in breast cancer type basal-like and low-grade glioma,the loss of ARID1A copy number was related with the decrease of the infiltration most immune cell infiltration levels(P<0.05). Conclusion: In intrahepatic cholangiocarcinoma,the loss of ARID1A expression is inversely correlated with the infiltration of CD4+,CD8+ T lymphocytes and CD163+ macrophages in the tumor microenvironment,while the infiltration of CD163+ macrophages is negatively correlated with survival prognosis.

参考文献/References:

[1] HAUSE R J,PRITCHARD C C,SHENDURE J,et al. Classification and characterization of microsatellite instability across 18 cancer types [J]. Nat med,2016,22(11): 1342-1350.
[2] RAZUMILAVA N,GORES G J. Cholangiocarcinoma[J]. Lancet,2014, 383(9935): 2168-2179.
[3] BRIGGS C D,NEAL C P,MANN C D,et al. Prognostic molecular markers in cholangiocarcinoma: a systematic review[J]. Eur J Cancer,2009,45(1):33-47.
[4] ZHANG H,YANG T,WU M,et al. Intrahepatic cholangiocarcinoma:Epidemiology,risk factors,diagnosis and surgical management[J]. Cancer Lett,2016,379(2): 198-205.
[5] RIZVI S,KHAN S A,HALLEMEIER C L,et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol,2018,15(2): 95-111.
[6] JIAO Y,PAWLIK T M,ANDERS R A,et al. Exome sequencing identifies frequent inactivating mutations in BAP1,ARID1A and PBRM1 in intrahepatic cholangiocarcinomas[J]. Nat Genet,2013,45(12): 1470-1473.
[7] WU R C,WANG T L,SHIH IE M. The emerging roles of ARID1A in tumor suppression [J]. Cancer Biol Ther,2014,15(6): 655-664.
[8] YANG S Z,WANG A Q,DU J,et al. Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma[J]. World J Gastroenterol,2016,22(25): 5814-5821.
[9] KIM Y B,HAM I H,HUR H,et al. Various ARID1A expression patterns and their clinical significance in gastric cancers[J]. Hum Pathol,2016,49:61-70.
[10] LI J,WANG W C,ZHANG Y J,et al. Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy[J]. J Clin Invest,2020,130(5):2712-2726.
[11] SHEN J,JU Z,ZHAO W,et al. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade[J]. Nat Med,2018,24(5):556-562.
[12] SUN X,WANG S C,WEI Y,et al. Arid1a has context-dependent oncogenic and tumor suppressor functions in liver cancer[J]. Cancer cell,2017,32(5):574-589.
[13] FENG Y,TANG X,LI C,et al. ARID1A is a prognostic biomarker and associated with Immune Infiltrates in hepatocellular carcinoma[J]. Can J Gastroenterol Hepatol,2022,2022:3163955.
[14] WANG X,NAGL N G,JR FLOWERS S,et al. Expression of p270 (ARID1A),a component of human SWI/SNF complexes,in human tumors[J]. Int J Cancer,2004,112(4): 636-642.
[15] MAMO A,CAVALLONE L,TUZMEN S,et al. An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer[J]. Oncogene,2012,31(16):2090-2100.
[16] HE F,LI J,XU J,et al. Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma[J]. J Exp Clin Cancer Res,2015,34(1):47.
[17] BI C,LIU M,RONG W,et al. High Beclin-1 and ARID1A expression corelates with poor survival and high recurrence in intrahepatic cholangiocarcinoma: a histopathological retrospective study[J]. BMC cancer,2019,19(1): 213.
[18] NAJAFI M,GORADEL N H,FARHOOD B,et al. Macrophage polarity in cancer:a review[J]. J Cell Biochem,2019,120(3):2756-2765.
[19] EVRARD D,SZTURZ P,TIJERAS-RABALLAND A,et al. Macrophages in the microenvironment of head and neck cancer: potential targets for cancer therapy [J]. Oral Oncol,2019,88:29-38.
[20] ALMATROODI S A,MCDONALD C F,DARBY I A,et al. Characterization of M1/M2 tumour-associated macrophages(TAMs)and Th1/Th2 cytokine profiles in patients with NSCLC[J]. Cancer Microenviron,2016,9(1):1-11.
[21] YAMAGUCHI T,FUSHIDA S,YAMAMOTO Y,et al. Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination[J]. Gastric Cancer,2016,19(4):1052-1065.
[22] NIINO D,KOMOHARA Y,MURAYAMA T,et al. Ratio of M2 macrophage expression is closely associated with poor prognosis for angioimmunoblastic T-cell lymphoma(AITL)[J]. Pathol Int,2010, 60:278-283.
[23] KOMOHARA Y,HASITA H,OHNISHI K,et al. Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma[J]. Cancer Sci,2011,102:1424-1431.
[24] HASITA H,KOMOHARA Y,OKABE H,et al. Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma [J]. Cancer Sci,2010,101:1913-1919.
[25] HU G,TU W,YANG L,et al. ARID1A deficiency and immune checkpoint blockade therapy:from mechanisms to clinical application[J]. Cancer Lett,2020,473:148-155.

相似文献/References:

备注/Memo

备注/Memo:
基金项目 天津医科大学肿瘤医院肿瘤外科精准治疗技术建设项目(ZLWKJZZL14)
作者简介 张泽武(1995-),硕士在读,研究方向:肿瘤学;通信作者:张伟,E-mail:zhangweitjch@163.com。
更新日期/Last Update: 2022-09-20