ChiCTR2500095303 版本V1.0 版本创建时间2025/01/06 09:34:15 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2500095303 

最近更新日期：

Date of Last Refreshed on：

 2025-01-06 09:34:06 

注册时间：

Date of Registration：

 2025-01-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

经外周血单细胞测序表征不同BCLC分期肝癌患者免疫浸润特征的研究

Public title：

Identification of peripheral blood immune infiltration signatures in hepatocellular carcinoma patients with different BCLC stages by single-cell sequencing

注册题目简写：

English Acronym：

研究课题的正式科学名称：

经外周血单细胞测序表征不同BCLC分期肝癌患者免疫浸润特征的研究

Scientific title：

Identification of peripheral blood immune infiltration signatures in hepatocellular carcinoma patients with different BCLC stages by single-cell sequencing

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

牛翔科 

研究负责人：

牛翔科 

Applicant：

Xiangke Niu 

Study leader：

Xiangke Niu 

申请注册联系人电话：

Applicant telephone：

 +86 18215512102

研究负责人电话：

Study leader's
telephone：

+86 28 86436383

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 niu19850519@163.com

研究负责人电子邮件：

Study leader's E-mail：

 niu19850519@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

成都市二环路北二段82号

研究负责人通讯地址：

二环路北二段82号

Applicant address：

No.82, North 2nd Section, 2nd Ring Road

Study leader's address：

The Second Ring Road in the Northern Second Section of No. 82 in Jinniu District, Chengdu, Sichuan Province, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

成都大学附属医院

Applicant's institution：

Affiliated Hospital of Chengdu University

研究负责人所在单位：

成都大学附属医院

Affiliation of the Leader：

Affiliated Hospital of Chengdu University

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 PJ2024-101-02

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

成都大学附属医院医学伦理委员会

Name of the ethic committee：

Ethics committee of Clinical Medical College&Affiliated Hospital of Chengdu University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-11-29 00:00:00

伦理委员会联系人：

刘弘毅

Contact Name of the ethic committee：

liuhongyi

伦理委员会联系地址：

二环路北二段82号

Contact Address of the ethic committee：

The Second Ring Road in the Northern Second Section of No. 82 in Jinniu District, Chengdu, Sichuan Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 28 86436383

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 cdfyllwyh@163.com

研究实施负责（组长）单位：

成都大学附属医院

Primary sponsor：

Affiliated Hospital of Chengdu University

研究实施负责（组长）单位地址：

二环路北二段82号

Primary sponsor's address：

The Second Ring Road in the Northern Second Section of No. 82 in Jinniu District, Chengdu, Sichuan Province, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川

市(区县)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

成都大学附属医院

具体地址：

二环路北二段82号

Institution
hospital：

Affiliated Hospital of Chengdu University

Address：

The Second Ring Road in the Northern Second Section of No. 82 in Jinniu District, Chengdu, Sichuan Province, China

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

without involving

研究疾病：

肝硬化无合并肿瘤的患者、肝癌不同BCLC分期的患者(0-D期)  

Target disease：

Individuals who have cirrhosis but no concurrent malignancies, as well as those with varying BCLC stages of hepatocellular carcinoma patients?(stages 0-D)

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

横断面 

Study design：

Cross-sectional 

研究目的：

采用单细胞测序表征BCLC不同分期患者外周血单细胞层面肿瘤免疫微环境的异质性，为肝癌靶免治疗启动时期和靶点选择提供依据。  

Objectives of Study：

In order to determine the initiation period and target selection for targeted immunotherapy in hepatocellular carcinoma, single-cell sequencing was utilized to characterize the heterogeneity of the tumor immune microenvironment at the peripheral blood single-cell level in patients with varying stages of BCLC.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

18岁≤年龄≤70岁；
1.受试者符合欧洲肝脏研究学会(EASL)2018诊断标准(EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma)，具体为：要求在同时满足以下条件中的①+②a两项或者①+②b+③三项时，可以确立HCC的临床诊断：①具有肝硬化以及HBV和/或HCV感染（HBV和/或HCV抗原阳性）的证据；②典型的HCC影像学特征：多排螺旋CT扫描和/或动态对比增强MRI检查显示肝脏占位在动脉期快速不均质血管强化，而静脉期或延迟期快速洗脱。a如果肝脏占位直径≥2cm，CT和MRI两项影像学检查中有一项显示肝脏占位具有上述肝癌的特征，即可诊断HCC；b如果肝脏占位直径为1-2cm，则需要CT和MRI两项影像学检查都显示肝脏占位具有上述肝癌的特征，方可诊断HCC，以加强诊断的特异性；③血清AFP≥400μg/L持续1个月或≥200μg/L持续2个月，并能排除其他原因引起的AFP升高，包括妊娠、生殖系胚胎源性肿瘤、活动性肝病及继发性肝癌等；
2.肝硬化受试者符合欧洲肝脏研究学会(EASL)2018诊断标准(EASL Clinical Practice Guidelines on non-invasive tests forevaluation of liver disease severity and prognosis - 2021 update)，具体为如果未行肝组织病理学检查，符合以下5条中2条以上且除外非肝硬化性门静脉高压者，可临床诊断为肝硬化：①胃镜检查显示食管胃静脉曲张；②影像学检查：超声、CT或MRI有肝硬化的影像学特征；③肝脏弹性测定：LSM＞13 kPa；④肝脏合成功能减低表现：血清白蛋白降低、凝血酶原时间延长；⑤脾功能亢进表现：血小板、白细胞或血红蛋白降低等；
3.临床资料如肿瘤标志物、肿瘤大小、形态、血液生化及影像学等相关资料完整；
4.无心、脑、肺、肾等重要脏器功能障碍的受试者。

Inclusion criteria

Age 18 to 70; 1.Patients meet the European Association for the Study of the Liver (EASL) 2018 diagnostic criteria (EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma), which require that the clinical diagnosis of HCC can be established when two of the following conditions are simultaneously met: (i) evidence of cirrhosis and HBV and/or HCV infection (HBV and/or HCV antigen); (ii) typical imaging of HCC. The clinical diagnosis of HCC can be established by: (1) evidence of cirrhosis and HBV and/or HCV infection (HBV and/or HCV antigen-positive); (2) typical imaging features of HCC: rapid heterogeneous vascular enhancement of hepatic occupations in the arterial phase with rapid elution in the venous or delayed phases on multislice CT scanning and/or dynamic contrast-enhanced MRI; and (3) a fast elution of the hepatic occupation in the venous or delayed phases. 2cm in diameter, one of the two imaging tests, CT and MRI, shows that the liver occupancy has the characteristics of hepatocellular carcinoma as described above, then the diagnosis of HCC can be made. b If the diameter of the liver occupancy is 1-2cm, both CT and MRI imaging tests need to show that the liver occupancy has the characteristics of hepatocellular carcinoma as described above, then the diagnosis of HCC can be made, in order to enhance the diagnostic specificity. c) serum AFP ≥ 400 μg/L lasting for 1 month or ≥ 200 μg/L lasting for 1 month or ≥ 200 μg/L lasting for 2 months. (iii) Serum AFP ≥400μg/L for 1 month or ≥200μg/L for 2 months, and other causes of AFP elevation can be ruled out, including pregnancy, germline embryonic tumors, active liver disease and secondary hepatocellular carcinoma; 2.Cirrhotic patients met the European Association for the Study of the Liver (EASL) 2018 diagnostic criteria (EASL Clinical Practice Guidelines on non-invasive tests forevaluation of liver disease severity and prognosis - 2021 update), specifically, if liver histopathology is not performed, cirrhosis can be clinically diagnosed if more than 2 of the following 5 items are met and non-cirrhotic portal hypertension is excluded: ① Gastroscopy shows esophagogastric venous varices; ② Imaging: ultrasonography, CT, or MRI have imaging features of cirrhosis; ③ Liver elastometry: LSM > 13 kPa; ④ Liver synthetic Liver synthesis: decrease in serum albumin, prolongation of prothrombin time; ⑤ hypersplenism: decrease in platelets, white blood cells or hemoglobin, etc; 3.Complete clinical data, such as tumor markers, tumor size, morphology, blood biochemistry, imaging, and other relevant information; 4.Participants without significant heart, brain, lung, kidney, or other organ disease.

排除标准：

1.已明确诊断为原发性肝癌并接受过治疗的受试者；
2.肝脏转移性肿瘤和合并其他肿瘤的受试者；
3.临床数据不完整的受试者；
4.临床诊断肝硬化合并肿瘤的受试者；

Exclusion criteria：

1.Subjects have been definitively diagnosed and treated for primary liver cancer;
2.Subjects having metastatic liver cancers and a mix of additional tumors;
3.Subjects having incomplete clinical data;
4.Subjects having a clinical diagnosis of cirrhosis combined with a tumor;

研究实施时间：

Study execute time：

从 From 2024-12-20 00:00:00至 To 2025-12-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-01-10 00:00:00 至 To 2025-10-30 00:00:00

干预措施：

Interventions：

组别：

肝硬化无肝癌发生受试者、BCLC分期0-D期受试者

样本量：

 18

Group：

participants with cirrhosis without hepatocellular carcinoma, participants with BCLC staging 0-D

Sample size：

干预措施：

不涉及

干预措施代码：

Intervention：

without involving

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川 

市(区县)：

  

Country：

China

Province：

Sichuan

City：

单位(医院)：

 成都大学附属医院 

单位级别：

 三级甲等 

Institution
hospital：

Affiliated Hospital of Chengdu University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

基因表达

指标类型：

主要指标

Outcome：

without involving

Type：

Primary indicator

测量时间点：

患者入组签署知情同意书后

测量方法：

基于Drop—Seq技术原理，依次将准备好的单细胞悬液、油、beads磁珠加入C4 scRNA载片与装置中，将细胞悬液制备成液滴，在液滴中完成细胞裂解及磁珠捕获mRNA的过程；随后将cDNA进行扩增纯化，Oligo文库构建，片段化，加接头，最后得到DNA纳米球；通过联合探针锚定聚合技术(cPAS)进行测序。

Measure time point of outcome：

Following subjects enrollment and the signing of the informed consent form

Measure method：

Based on the principle of Drop-Seq technology, prepared single-cell suspension, oil, and beads magnetic beads were sequentially added into C4 scRNA carrier and device, and the cell suspension was prepared into a droplet, in which the process of cell lysis and magnetic beads capturing mRNA was completed; subsequently, the cDNA was amplified and purified, the Oligo library was constructed, fragmented, and spliced, and finally DNA nanospheres were obtained; sequencing was performed by co-probe anch

指标中文名：

外周血免疫浸润状态

指标类型：

主要指标

Outcome：

Peripheral blood immune infiltration status

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

静脉外周血

组织：

Sample Name：

Peripheral venous blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 70 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

无

Blinding：

None

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

不适用

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

not available

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

根据本临床研究目标而自主设计的病例报告表（case report form, CRF）记录所需实验数据

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Documentation of required experimental data on an in-house case report form (CRF) developed to meet the clinical study's objectives.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-01-06 09:34:06