The Application of Extracellular Vesicle Detection in Gastric Juice Based on Metamaterial Sensing in the Diagnosis of Gastric Cancer and Related Diseases
Conditions: Gastric Cancer (GC), Gastric Cancer (Diagnosis)
Sponsor: Beijing Friendship Hospital

Clinical research protocol
The application of extracellular vesicle detection in gastric juice based on
metamaterial sensing in the diagnosis of gastric cancer and related diseases
Institution
Beijing Friendship Hospital, Capital Medical University
Project leader
Li Min
Version
V1
Date
2025.12.28

1. Research background
Gastric cancer is an important type of cancer worldwide, ranking fifth in terms of
global cancer incidence and fourth in terms of mortality.[1] In fact, the majority of
gastric cancer cases are diagnosed at an advanced stage, with a poor prognosis and
limited treatment options.[2] The 5-year survival rate for early-stage gastric cancer is
over 90%, while that for advanced gastric cancer is only about 10%.[3]
Therefore, early and precise endoscopic examination is of great significance in
reducing the mortality rate of gastric cancer and improving the prognosis of patients.
Gastric juice is a digestive fluid that directly contacts the gastric tissue and bypasses
the metabolic function of the liver. It contains a large number of shed malignant cells
and tumor products, which makes it possible to be an ideal biomarker with
satisfactory sensitivity and specificity.[4]
At present, many researchers have begun to focus on gastric juice as a research
subject, mainly concentrating on the study of nucleic acid molecules such as miRNA,
cirRNA, lncRNA, and microRNA in gastric juice. These molecules are believed to be
related to the development and progression of gastric cancer and thus can be used for
the diagnosis and prognosis analysis of gastric cancer.[5，6，7]
In the existing research, studies on extracellular vesicles in gastric juice are
scarce. As an important component of functional molecules in the body, extracellular
vesicles play a key role in the development and progression of diseases. By deeply
exploring the composition of extracellular vesicles in gastric juice, we can investigate
their potential role in the development of gastric cancer, search for possible
biomarkers, and thereby provide new clues and basis for the early diagnosis,
prognosis assessment, and treatment strategy formulation of gastric cancer.
References
[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer
J Clin. 2021. 71(3): 209-249.
[2] Necula L, Matei L, Dragu D, et al. Recent advances in gastric cancer early diagnosis.
World J Gastroenterol. 2019. 25(17): 2029-2044.

[3] Luo M, Li L. Clinical utility of miniprobe endoscopic ultrasonography for prediction
of invasion depth of early gastric cancer: A meta-analysis of diagnostic test from PRISMA
guideline. Medicine (Baltimore). 2019. 98(6): e14430.
[4] Shao J, Fang PH, He B, Guo LL, Shi MY, Zhu Y, Bo P, Zhen-Wen ZW.
Downregulated MicroRNA-133a in Gastric Juice as a Clinicopathological Biomarker for
Gastric Cancer Screening. Asian Pac J Cancer Prev. 2016;17(5):2719-22.
[5] Shao Y, Tao X, Lu R, Zhang H, Ge J, Xiao B, Ye G, Guo J. Hsa_circ_0065149 is an
Indicator for Early Gastric Cancer Screening and Prognosis Prediction. Pathol Oncol Res.
2020 Jul;26(3):1475-1482.
[6] Fei ZH, Yu XJ, Zhou M, Su HF, Zheng Z, Xie CY. Upregulated expression of long
non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients
with gastric cancer. Tumour Biol. 2016 Feb;37(2):1983-93. doi: 10.1007/s13277-015-3979-9.
Epub 2015 Sep 3.
[7] Retracted: Chen, Y, Zhang, W, Kadier, A, Zhang, H, Yao, X. MicroRNA-769-5p
suppresses cell growth and migration via targeting NUSAP1 in bladder cancer. J Clin Lab
Anal. 2020; 34:e23193. J Clin Lab Anal. 2023 Apr;37(8):e24893.
2. Purpose of research
This project aims to study extracellular vesicles in gastric juice under different
disease conditions, screen out liquid biopsy markers for the early diagnosis of gastric
cancer, and identify biomarkers for disease progression or high-risk populations to
achieve early disease prediction, guide endoscopic detailed examination, and reduce
missed diagnoses. The research will be conducted at Beijing Friendship Hospital,
Capital Medical University. By analyzing the diagnosis and treatment process and
gastric juice samples of patients undergoing gastroscopy, the characteristics of
extracellular vesicles in gastric cancer patients will be determined, and further
guidance for endoscopic detailed examination will be provided. We will conduct the
research in accordance with the "Measures for the Ethical Review of Biomedical
Research Involving Human Subjects" and the principles of the "Declaration of
Helsinki".
3. Research contents
After obtaining informed consent from the patients, all the medical history and
treatment records of the patients who underwent gastroscopy since the onset of the
disease, as well as gastric fluid samples, including laboratory and imaging data, were
collected and recorded. The medical history and treatment records and gastric fluid
samples were analyzed and an article was written.

4. Study protocol
4.1. Study design
Observational study (retrospective)
4.2. Subjects
4.2.1 Study population: patients who underwent gastroscopy and treatment in Beijing
Friendship Hospital, Capital Medical University from Dec. 2025 to Dec. 2026.
4.2.2 Research Center: Beijing Friendship Hospital Affiliated to Capital Medical
University.
4.2.3 Planned enrollment: 100 patients, in which the ratio of gastric cancer and
non-cancer patients was 1:1.
4.2.4 Inclusion and exclusion criteria
Inclusion criteria: 1. Patients underwent gastroscopy and treatment at the Endoscopy
Center of Beijing Friendship Hospital, Capital Medical University, and received
pathological biopsy. 2. Previous gastroscopy suggested the possibility of lesions. 3.
No previous history of gastrointestinal cancer.
Exclusion criteria: 1. Patients could not cooperate with the examination or had
contraindications to endoscopy. 2. Previous history of gastrointestinal tumors,
gastrointestinal surgery, physical and chemical injuries of the gastrointestinal tract. 3.
Severe bile reflux. 4. Take simethicone and other defoaming agents before
examination. 5. Patients with serious diseases of heart, lung, kidney, brain, blood and
other important organs.
4.3 Research process
1. Patients who met the inclusion criteria were enrolled, and the demographic and
medical information of the subjects were collected, including name, gender, age,
primary disease, past history, gastroscopic biopsy pathological report, etc.
2. the use of previous studies in gastroscopy drain to collect the clinical routine
during the rest of the specimens of gastric juice, extracellular vesicle separation and
metabonomics analysis, about 10 to 20 ml/time, according to the result of pathology
for specimens of patients with gastric cancer patients and patients with gastric cancer
group, the identification of potential biomarkers, diagnosis model is established.

4.4 Observation target
(1) Demographic data and clinical information: name, age, gender;
(2) Pathological results of endoscopic tissue biopsy;
(3) Physical and chemical properties of gastric juice (pH value, absorbance, etc.);
(4) Diagnostic analysis of extracellular vesicles in gastric juice.
4.5 Determination of Sample Size
This study is an observational and descriptive one, with no specific sample size
requirement. However, based on current domestic and international literature reports,
approximately 100 cases are expected to be needed. Meanwhile, adjustments will be
made as appropriate considering the situation of patient loss to follow-up and
incomplete sample information in our center that cannot be used.
4.6 Informed consent situation
After confirming that the patients meet the inclusion and exclusion criteria, the
principal investigator informs all the subjects of the experimental protocol. With the
patients' consent, they sign the informed consent form.
4.7 Confidentiality of research information
The personal information of the subjects will be processed, stored and used in an
anonymous manner. The information and data generated during the research process
will be properly kept in accordance with the regulations. After the research is
completed, the publication of the research results will not disclose the personal
information of the subjects.
5. Technical route

6. Statistical method
Statistical software SPSS19.0 was used to analyze the data of this cohort study, and P
value < 0.05 was considered statistically significant. For quantitative data, if the data
were in accordance with the normal distribution, the mean ± standard deviation was
used to describe the data. The t test was used for comparison between two groups, and
the one-way analysis of variance was used for comparison between multiple groups.
If the data did not meet the normal distribution, "median" was used to describe the
data, and the differences were compared using the Mann-Whitney rank sum test. For
qualitative data, "rate (95%CI)" was used to describe, chi-square test was used to
compare the differences between groups, and Logistic regression was used for
cross-sectional multivariate analysis of risk factors.
7. Quality Control
Formulate
research
plans
to
ensure
the
accuracy,
completeness
and
comprehensiveness of data; record and preserve relevant documents for the purpose
of
retracing
the
quality
control
process;
strictly
keep
patients'
information
confidential.
8. Description of Team Members' Qualifications and Division of Labor
Li Min (digestive internal medicine): project director, signed the participants informed
consent.
Hao-Su Zhan (digestive internal medicine): responsible for screening/participants into
groups, data collection, etc