Evaluation of AKR1B10 as a New Marker for Interventional Therapy of Hepatocellular Carcinoma
Conditions: Hepatocellular Carcinoma
Sponsor: Hebei Medical University Third Hospital

Evaluation of AKR1B10 as a New Marker for
interventional therapy of Hepatocellular Carcinoma
Research Plan
Plan Number: AKR-TACE-001
Plan Date: 12/1/2022
Sponsor: Yuemin Nan
Responsible department: Integrated Traditional Chinese and
Western Medicine Hepatology Department

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Evaluation of AKR1B10 as a New Marker for
interventional therapy of Hepatocellular Carcinoma
1.
Research background
Primary liver cancer is currently the fourth most common malignant tumor and the second
leading cause of tumor mortality in China, posing a serious threat to the lives and health of the
Chinese people [1]. Primary liver cancer mainly includes three pathological types: hepatocellular
carcinoma (HCC), cholangiocarcinoma (CC), and mixed type, with HCC accounting for 85% to
90% [2]. According to the Diagnosis and Treatment Guidelines for Primary Liver Cancer (2022
Edition) [3], after comprehensive evaluation of various indicators of patients, surgery is considered
the preferred treatment method for radical liver cancer treatment. However, most patients have
varying degrees of liver cirrhosis, and some patients cannot tolerate surgical treatment. In this case,
non-surgical treatment methods are often used
[4], such as radiofrequency ablation (RFA),
including microwave ablation (MWA), anhydrous ethanol injection (PEI), etc., Transcatheter
arterial chemoembolization (TACE), radiation therapy, and systemic anti-tumor therapy [5] which
also known as systemic therapy, mainly refers to anti-tumor therapy, including molecular targeted
drug therapy, immunotherapy, chemotherapy, and traditional Chinese medicine treatment; in
addition, it also includes treatment for basic liver cancer diseases, such as antiviral therapy, liver
and gallbladder protection, and supportive symptomatic treatment.
At present, whether it is surgical treatment or non-surgical treatment, commonly used liver
cancer related biomarkers in clinical practice during the evaluation of treatment efficacy or regular
follow-up of patients include AFP, AFP-L3%, DCP, etc. [6,7], but there are no reports on whether
AKR1B10 can be used for the efficacy evaluation of these treatment methods.
In the early stage, a research team detected the levels of AKR1B10 in serum samples from
477 normal individuals, 107 benign liver tumors, 32 patients with chronic hepatitis B, 78 patients
with liver cirrhosis, and 482 patients with liver cancer, and evaluated its early diagnostic value in
liver cancer. It was found that AKR1B10 protein, as a serum marker for liver cancer [8], had
significantly better performance than AFP, mainly reflected in three aspects: first, it is more
sensitive, The normal background level (reference range) of AKR1B10 is significantly lower than
AFP, which means that during clinical testing, changes in serum concentration are more
pronounced, making it easier to identify asymptomatic early liver cancer patients; Secondly, it is
more specific and has a higher detection rate for liver cancer, with lower false positive and false
negative rates. In addition, more than 70% of liver cancer patients who test negative for AFP will
be tested positive for AKR1B10, resulting in lower rates of missed diagnosis and misdiagnosis;
Thirdly, the time to reflect changes in the condition is 6-7 times faster than AFP. The half-life of
AKR1B10 is 23 hours, while AFP has a half-life of 6-7 days. Postoperative AKR1B10 testing can
help liver cancer patients determine surgical outcomes earlier, providing scientific basis for
doctors to develop reasonable postoperative treatment plans. Therefore, this project aims to
explore the clinical value of AKR1B10 in evaluating the efficacy of liver cancer treatment.
2.
Research purpose

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2.1
Main purpose
Evaluate the clinical value of serum AKR1B10 as a marker of the interventional therapy in
patients with primary liver cancer (N=200).
2.2
Secondary objectives
Evaluate the clinical value of serum AKR1B10 in combination with AFP and DCP in the
interventional therapy in patients with primary liver cancer.
3.
Research Methods and Content
3.1
Research design
This study aims to detect the dynamic changes of AKR1B10 in the treatment process of
primary liver cancer patients and evaluate the clinical value of this tumor indicator in monitoring
the therapeutic efficacy of liver cancer treatment.
3.2
Study population
All participants will sign an informed consent form, agreeing that their samples and related
information can be used for this medical studies. The relevant standards are as follows:
3.2.1 Inclusion Criteria
(1)
age between 18 and 80
(2)
diagnosis of HCC according the AASLD criteria
(3)
TACE is planned
(4)
resection is impossible
(5)
No significant underlying medical illness affecting patient's survival
(6)
Patients available for regular follow-up according to the study protocol
3.2.2 Exclusion criteria:
(1) Previous history of other tumors;
(2) Combined with other tumors;
(3) Patients who have received blood transfusions within one month;
(4) The patient was unable to participate in this study for other reasons.
3.2.3 Midway exit criteria
(1) The patient or their guardian has decided to withdraw from the study at any time without any
adverse circumstances affecting them and without the need to provide a reason.
(2) If the patient's physician deems it no longer appropriates for them to continue participating in
the study, they may withdraw from the study at any time.
3.3
Research contents
This project collects serum samples of primary liver cancer patients (N=200) who have
received initial diagnosis and are planning to receive treatment in our hospital. The serum will be

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collected in 3 day before treatment and then a serum will be collected 3-5 days again after
treatment. Thereafter, serum samples will be collected in the monthly regular follow-ups of the
patients. The specific implementation plan is as follows:
（1）
Sample preparation and requirements: Approximately 2-5 ml venous blood will be
collected and then centrifuged at 4 ℃, 4000g for 10 minutes. This study will use the discarded
procoagulant serum.
（2）
The supernatant serum will be transferred into a 1.5mL EP tube and stored at -80 ℃for
use.
（3）
Serum levels of AKR1B10, AFP, and DCP will be measured. The decline rates,
magnitudes, and lowest levels of AKR1B10, AFP, and DCP after treatment will be analyzed.
Dynamic curves of serum levels of AKR1B10, AFP, and DCP before and after treatment will
be drawn to construct a dynamic change model. The clinical data of patients, such as gender,
age, HBsAg, liver function, imaging data, and other clinical information will be dynamically
queried and recorded.
（4）
Dynamic curves of AKR1B10, AFP, and DCP in serum levels before and after treatment
will be drawn.
（5）
The relationship between the dynamic changes of AKR1B10, AFP, and DCP alone or in
combination with imaging data, histological types, and tumor size and number (tumor burden)
will be analyzed.
（6）
Pay attention to the phenomenon of temporary elevation of AKR1B10 after treatment as
the death of cancer cells and non-specific release of intracellular proteins, including
AKR1B10, as well as the potentials unable to decrease to normal levels and an elevation after
reduction of these markers. Combination analysis with other clinical phenotypes will be
conducted to solve the potential issues.
4.
Research related ethics
4.1
Ethics Committee Review
This protocol, written informed consent form, and materials directly related to the subjects
must be submitted to the ethics committee for written approval before the study can be officially
conducted. Researchers must submit their annual research report to the ethics committee at least
annually (if applicable). When the study is terminated and/or completed, the researcher must
notify the ethics committee in writing; Researchers must promptly report all changes that have
occurred in their research work to the ethics committee (such as revisions to protocols and/or
informed consent numbers), and these changes must not be implemented without approval from
the ethics committee, unless they are made to eliminate obvious and direct risks to the subjects.
When such situations occur, the ethics committee will be notified.
4.2
Informed consent
The procedure for obtaining informed consent: The researcher must provide the subject or
their legal representative with an easily understandable and approved informed consent form by
the ethics committee, and give the subject or their legal representative sufficient time to consider
the study. Before obtaining a signed written informed consent form from the subject, the subject is

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not allowed to participate in the study. During the participant period, all updated versions of the
informed consent form and written information will be provided to the participants. The informed
consent form should be kept as an important document for clinical trials for future reference.
Note: In this project, a dedicated person will be arranged to obtain the patient's informed
consent form.
4.3
Confidentiality measures
The results of this project may be published in medical journals, but we will keep patient
information confidential in accordance with legal requirements, and only display codes externally.
Unless required by relevant laws, patient personal and clinical information will not be disclosed.
When necessary, government management departments, hospital ethics committees, and their
relevant personnel may access patient information in accordance with regulations.
4.4
Regarding research expenses and related compensation
The testing fees in this project will be paid by our project team, and you do not need to pay
any fees. The results of this study can provide a basis for personalized and precise diagnosis and
treatment of liver cancer patients, enabling them to benefit the most from this clinical study. In
addition, participating in this study will not incur any additional costs related to diagnosis and
treatment of your illness.
5.
Risks and Benefits
5.1
Risks associated with participating in this study
This study will use the discarded procoagulant serum that has been used for clinical diagnosis
purposes and has no impact on the relevant diagnosis and treatment activities of patients.
5.1
Project benefits
The results of this study can evaluate the changes of AKR1B10 in the treatment stage of liver
cancer patients, and also help to evaluate the therapeutic effect of liver cancer treatment from a
new perspective, providing a theoretical basis for achieving personalized and accurate diagnosis
and treatment of liver cancer patients.
6.
Annual Implementation Plan
From January to June 2024, serum levels of AKR1B10, AFP, and DCP will be detected in
patients with primary liver cancer before and after interventional treatment.
Establish a study queue for primary liver cancer patient follow-up studies.

January - December 2024: Enrollment and maintenance of the study cohort for patients with
primary liver cancer, measurement of serum AKR1B10, AFP, and DCP levels, and combining
analysis of AKR1B10, AFP, and DCP data alone or in combination with imaging results and
other clinical data.

January - June 2025: Clinical cohort study will be concluded.
Continue to follow up with enrolled liver cancer patients, record their diagnosis and treatment
history, recurrence, and survival status, and then comprehensively analyze clinical research

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data and AKR1B10, AFP, and DCP for evaluation of therapeutic efficacy, making a
conclusion.
7.
Reference
[1]. Zhou, M., et al., Mortality, morbidity, and risk factors in China and its
provinces, 1990-2017: a systematic analysis for the Global Burden of Disease
Study 2017. Lancet, 2019. 394(10204): p. 1145-1158.
[2]. Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J
Clin, 2018. 68(6): p. 394-424.
[3]. 原发性肝癌诊疗指南(2022 年版). 临床肝胆病杂志, 2022. 38(02): 第
288-303 ⻚.
[4]. Zhu, X.D., et al., Downstaging and Resection of Initially Unresectable
Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1
Antibody Combinations. Liver Cancer, 2021. 10(4): p. 320-329.
[5]. Wang, Z., et al., Adjuvant Transarterial Chemoembolization for HBV-Related
Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin
Cancer Res, 2018. 24(9): p. 2074-2081.
[6]. Tateishi, R., et al., Prediction of recurrence of hepatocellular carcinoma after
curative ablation using three tumor markers. Hepatology, 2006. 44(6): p. 1518-27.
[7]. Yoo, J., et al., Evaluation of a serum tumour marker-based recurrence
prediction model after radiofrequency ablation for hepatocellular carcinoma.
Liver Int, 2020. 40(5): p. 1189-1200.
[8]. Ye, X., et al., A Large-Scale Multicenter Study Validates Aldo-Keto
Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of
Hepatocellular Carcinoma. Hepatology, 2019. 69(6): p. 2489-2501.

Evaluation of AKR1B10 as a New Marker for
interventional therapy of Hepatocellular Carcinoma
Review and Approval
Plan Number: AKR-TACE-001
Plan Date: 12/1/2022
Sponsor: Yuemin Nan
Responsible department: Integrated Traditional Chinese and
Western Medicine Hepatology Department

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Review and approval documents from the Ethics Committee of
the Third Hospital of Hebei Medical University
Approval
Number
K2019-014-2
Project
Name
Evaluation of AKR1B10 as a New Marker for interventional therapy of
Hepatocellular Carcinoma
Plan
Number
AKR-TACE-001
Sponsor
Yuemin Nan
Responsible
department
Integrated Traditional Chinese and Western
Medicine Hepatology Department
Review
date
12/25/2023
Review
category
R Initial review
* Tracking review
* Annual/Regular Tracking Review
* Amendment review
Review of reports on serious adverse events and unexpected events
* Review of non-compliance/violation of plan events
Suspend or terminate approved research review
Closing review
Complaints from subjects
site visit
Review
Submissio
n
documents
Research protocol and informed consent form
Review
Committe
e Member
See the attendance form of the committee members
Review
opinions
Agree
Agree after
making
necessary
revisions
Review after
making
necessary
corrections
Disagree
Terminatio
n or
Suspensio
n
R
*
*
*
*
After review by this ethics committee, it has been agreed to conduct
this study in accordance with the agreed clinical research protocol and
informed consent form.
Attention:
1.
Please follow the GCP principles and follow the protocol agreed
upon by the ethics committee to conduct clinical research and
protect the health and rights of subjects.
2.
Please submit an amendment application for any modifications to

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the
research
protocol,
informed
consent
form,
recruitment
materials, etc.
3.
If SAE occurs, please submit a serious adverse event report in a
timely manner.
4.
If there is any non-compliance/violation of the plan, please submit
a violation report in a timely manner.
5.
Please submit research progress reports in a timely manner based
on the frequency of annual/regular tracking reviews.
6.
Please submit a report on the suspension or termination of clinical
research in a timely manner.
7.
Please submit a final report after completing the clinical study.
Annual
regular/trackin
g
review
frequency
3 months *
6 months *
9 months *
12 months R
contacts
Pei Guo
Phone
Number
17835683894
Signature of Chairman:
Date: 12/25/2023
Ethics Committee of the Third
Hospital
of
Hebei
Medical
University (Seal):
Date:12/25/2023

Evaluation of AKR1B10 as a New Marker for
interventional therapy of Hepatocellular Carcinoma
Informed Consent
Plan Number: AKR-TACE-001
Plan Date: 12/1/2022
Sponsor: Yuemin Nan
Responsible department: Integrated Traditional Chinese and
Western Medicine Hepatology Department

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Informed Consent
Dear friend:
You will be invited to participate in the study of the clinical application value of aldosterone
reductase 1B10 in liver cancer. Please read the following instructions carefully before deciding
whether to participate in this study. If you have any questions, please do not hesitate to ask, and
the researchers will answer them for you.
Your participation in this study is voluntary. This study has been reviewed by the ethics
review committee of this research institution.
1.
Research Background
Research Project Name: Evaluation of AKR1B10 as a New Marker for interventional therapy of
Hepatocellular Carcinoma
Research Unit Name: The Third Hospital of Hebei Medical University
Research Sponsor: Hunan Light of Life Biotechnology Co., Ltd
Project Leader and Contact Number: Nan Yuemin 18533112266
At present, there is an auxiliary diagnostic kit for liver cancer with aldo-keto reductase 1B10
(AKR1B10) protein as a tumor marker, namely the aldo-keto reductase 1B10 measurement kit
(magnetic particle chemiluminescence). A multicenter clinical study has detected serum samples
from 477 healthy people, 107 cases of benign liver tumors, 32 cases of chronic hepatitis B patients,
78 cases of liver cirrhosis patients and 482 cases of liver cancer patients. The results showed that
AKR1B10 protein as a serum marker of liver cancer has significantly better performance than AFP,
mainly reflected in three aspects: First, it is more sensitive. The normal baseline level (reference
range) of AKR1B10 is much lower than that of AFP, which means that in the clinical detection
process, the change of serum concentration is more obvious, and it is easier to identify
asymptomatic early liver cancer patients. Second, it is more specific, with a higher detection rate
of liver cancer, lower false positive and false negative rates, and more than 70% of liver cancer
patients with negative AFP detection will be positive for AKR1B10 detection, thus bringing lower
missed diagnosis rate and misdiagnosis rate; Third, the time to reflect the change of the disease is
6-7 times faster than that of AFP. The half-life of AKR1B10 is only 23 hours, while the half-life of
AFP is 6-7 days. Doctors can know the surgical effect earlier through AKR1B10 detection after
surgery, providing a scientific basis for doctors to make a reasonable postoperative treatment plan.
In addition, this method has been tested in three clinical trial institutions: Peking Union Medical
College Hospital (leading unit), Hunan Cancer Hospital, and Hunan Provincial People's Hospital.
The applicability and accuracy of this detection kit in clinical application have been preliminarily
completed. In order to further evaluate the value of AKR1B10 as a marker of liver cancer
treatment, it is planned to carry out this clinical verification work in The Third Hospital of Hebei
Medical University.
2.
Research Objectives
With the clue that the serum marker AKR1B10 we found earlier can be used as an effective
indicator for detecting HCC, we will conduct an in-depth study on AKR1B10 as a new tumor

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marker for TACE efficacy evaluation, so as to provide detailed clinical research data and scientific
basis for improving the survival rate of liver cancer patients.
If you agree to participate in this study, we will number each subject and establish a
research file. During the study, we need to collect some of your samples. Professionals will take
samples from you, using only the blood or pathological tissue wax remaining in the routine
treatment or routine diagnostic process, or extracting 4 ml venous blood from your arm. Your
samples will only be used for the study, will not affect the results of routine treatment or diagnosis,
and will not be used for any commercial activities.
3.
Risks and benefits
Your sample collection will be operated in strict accordance with aseptic requirements.
There may be some very small risks in blood sample collection, including transient pain, local
bruising, mild dizziness in a small number of people, or extremely rare needle infection; or only
the blood left in the routine treatment or routine diagnostic process, without additional risks. The
detection of your samples will help make a diagnosis of the disease, provide necessary advice for
your treatment, or provide useful information for the study of the disease.
4.
Privacy issues
If you decide to participate in this study, your participation in the test and personal
information in the test will be kept confidential. Your blood sample will be identified by the study
number rather than your name. Information that can identify you will not be disclosed to members
outside the research group unless you give permission. All research members are required to keep
your information confidential. When the results of this study are published, no personal
information will be disclosed.
5.
Free Withdrawal
You may choose not to participate in this study, or withdraw from the study by notifying the
investigator at any time. Your data will not be included in the study results, and your rights and
interests will not be affected.
6.
Contact Information
You can always get information and progress related to this study. If you have any questions
about this study, or about the rights and interests of participants in this study, you can contact Han
Fang at the project team at the phone number 13933847150.
I have read this informed consent. I have had the opportunity to ask questions and all
questions have been answered. I understand that participation in this study is voluntary. I may
choose not to participate in this study, or withdraw after notifying the investigator at any time
without discrimination or retaliation, and my rights and interests will not be affected. If I fail to
comply with the study plan, or any other reasons related to the study occur, the study leader may
terminate my participation in the study.

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I will receive a copy of the signed informed consent.
Name of Subject:
Signature of Subject:
(If a proxy is involved, the proxy's signature is
required)
Date:
I have accurately informed the subject of this document, he/she has accurately read this
informed consent, and I certify that the subject has had the opportunity to ask questions. I certify
that he/she has given voluntary consent.
Name of the study leader:
Signature of the study leader:
Date:
(Note: If the subject is illiterate, a witness is required to sign; if the subject is incapacitated, an
agent is required to sign)