Female Genital Tract Cancer Theranostics
Urinary Tract Cancer Theranostics
TAGMe DNA methylation detection
EPIPROBE
Why receive methylation detection?
H3C
CH3
Methylation
abnormalities
Genetic
mutations Cancerous Cells Cancer cell
proliferation
Cancer
metastasis
Methylation
detection
NGS
genetic
detection
CTC
detection
Biochemical
marker
detection Imaging
detection
Precancerous lesions Early stages of cancer Early to mid-stage cancer Advanced cancer
Discoverer of TAGMe
• Doctoral Supervisor of Fudan University, Chief Scientist of national "973" project,
• Changjiang Scholar Distinguished Professor, PI of Epigenetics Center of Fudan Biomedical
Research Institute.
• 2001-2007 Postdoctoral Fellow, Uppsala University, Sweden; Johns Hopkins University,
USA (tutored by Dr. Andy);
• In November 2007, Faculty and Associate Research Scientist of Columbia University.
Dr. Wenqiang Yu
Research findings
The whole genome DNA methylation sequencing method with independent
intellectual property right, Guided Positioning Sequencing (GPS) technology,
was established and Tumor Aligned General Methylated Epiprobe (TAGMe)
were discovered, which has been double-blind verified in 50000+ clinical
samples.
Discovery of TAGMe
Tumor Aligned General Methylated Epiprobe (TAGMe)
Research: From simple
to complex
Application: From
complex to simple
GPS method: covering 96% of the genome C (1.12G/1.17G);
WGBS method: covering 60 to 80% CpG of the genome.
Genome Research, 2019.01 (IF=11.1)
Cancer Research, 2019.10 (IF=12.7)
Clinical and Translational Medicine,
2021.06 (IF=11.5)
Frontiers in Molecular Biosciences (IF=5.2)
Signal Transduction and Targeted Therapy
（IF=38.104）
Technological breakthrough: TAGMe-DNA methylation detection method
Multiple DNA methylation
detection platforms
Establish a whole-process standardized system from sample
collection to report generation
Me-qPCR platform
Without bisulfite treatment
Automate DNA methylation
detection in one step
Applicable detection items
• Cervical cancer,
• Urinary tract cancer,
• Endometrial cancer
BS-qPCR VS Me-qPCR
Sample
collection
Nucleic acid
extraction (1h)
Bisulfite treatment
(2.5h)
Purification
(1h)
qPCR (2h)
Data analysis
Report
Sample
collection
Nucleic acid
extraction (1h)
qPCR (2h)
Data analysis
Report
Technical advantages without bisulfite treatment
• More stable
• More sensitive
• More convenient
• Automated
Main
experimental
Procedures
Original DNA methylation detection technology, based on qPCR platform that doesn’t require bisulfite treatment
-- Me-qPCR, can detect as low as 0.2% of tumor components.
Product quality: Double-blind validation
Limit of Detection: 0.2%
Double-blind validation of TAGMe
No. Cancer
type Sample type Sample
Number Partial research results Performance
1
Cervical
cancer
Cervical cells/vaginal secretions,
etc.
36348 Clin and Trans Med (2021.06, the latest IF is 11.5)
STTT（2022.07，IF 38.1）
94.3% specificity, 96% sensitivity (exfoliate
cells)
2
Urinary tract
carcinoma Urine/tissue, etc. 3499 Article is scheduled for publication in 2022 92.7% specificity, 82.1% sensitivity (urine)
3 Lung cancer Alveolar lavage fluid/pleural
fluid/tissue/blood, etc. 3385 Cancer Res (2019.10, the latest IF is 12.7) 96.5% specificity, 87% sensitivity (lavage
fluid/pleural fluid)
4
Endometrial
cancer
Cervical/uterine cavity
cells/tissues, etc. 884 Front Mol Biosci (2021.11, the latest IF is 5.2）
87.3% specificity, 90.9% sensitivity (exfoliate
cells)
5
Biliary tract
tumors
Bile/tissue, etc. 930 Article is scheduled for publication in 2022 100% specificity, 96.9% sensitivity (tissue)
6
Immunotherap
y
blood 746 Article is scheduled for publication in 2022 85.7% specificity, 66.7% sensitivity (Blood)
7 breast cancer Tissue/blood, etc. 150 R&D is in progress 92.5% specificity, 100% sensitivity (tissue)
8 Liver cancer Tissue/blood, etc. 979 Article is scheduled for publication in 2022 90.1% specificity, 82.2% sensitivity (tissue)
9 gastric cancer Tissue/blood, etc. 196 R&D is in progress 100% specificity, 90% sensitivity (tissue)
10 Colorectal
cancer
Feces/tissue/blood, etc. 189 R&D is in progress 90% specificity, 100% sensitivity (tissue)
11 Thyroid
cancer
Tissue 215 R&D is in progress -
12 Other Cerebrospinal fluid/bone
marrow smear/tissue/blood, etc. 971 R&D is in progress -
Summary: By the end of March 2022, total of 50552 clinical samples have been double-blind validated, and the overall
consistancy rate of tissue samples is >90%.
Cervical Cancer(TAGMe-CeCan) & Endometrial
Cancer(TAGMe-EnCan)
TAGMe
DNA methylation
detection for female
genital tract cancer
Eliminate the cancer in the precancerous stage
• DNA methylation in cervical high-grade lesions (HSIL) screening has a specificity of 95.2%, and sensitivity of 76.5%;
• Overall (≥HSIL) screening specificity is 95.2%, and sensitivity is 84.4%.
Product performance: better than HPV and TCT
Clinical and Translational Medicine.
2021.06 (IF=11.5)
• According to the analysis of the 3728 newly enrolled and unblinded samples in the double-blind verification, performance of DNA
methylation detection is as follows:
pathologic positive includes high-grade cervical lesions and cervical cancer patients, and pathology-negative refers to diseases that have not reached
high-grade lesions or cervical cancer.
94.7%
74.7%
84.4%
20.3%
51.2%
95.2%
Cervical Cancer Screening:
≥HSIL
Sensitivity Specificity
84.4%
95.2%
40.9%
99.4%
94.8%
Sensitivity Specificity PPV NPV Compliance
Rate
Performance of DNA methylation
76.5%
95.2%
Sensitivity Specificity
DNA Methylation
Detection：HSIL
Product performance: screen precancerous lesions
Further analysis of the detection performance of DNA methylation detection in different stages found that the detection rate in the cancer group was 100%, and
the detection rate in the high-grade lesion group was 76.5%.
Results of double-blind validation
4.3%
10.7%
73.7% 75.0%
78.8%
100.0% 100.0% 100.0% 100.0%
76.5%
100.0%
Normal CIN 1 CIN 2 CIN 3 CIN 2+3 CIS CAC CSCC EC HISL CA
Positive detection rate of DNA methylation in different disease stages
Clinical pain points of endometrial cancer screening
Early endometrial cancer is confined to the uterus
Pain point: Lacking sensitive and accurate non-invasive screening method. Symptoms such as
early irregular vaginal bleeding and vaginal drainage are easily overlooked, missing the
opportunity for early diagnosis.
Endometrial biopsy may result in
discomfort, bleeding, infection, and
uterine perforation, with a high rate of
missed tests
Transvaginal ultrasonography:
Convenient and noninvasive, vaginal ultrasound is easy to miss diagnosis when the
endometrium is <5 mm thick and hard to assess premenopausal endometrial lesions.
Hysteroscopy:
Expensive, most patients require anesthesia, and has the risk of side effect(e.g.
infection, water intoxication, air embolism, etc.), thus cannot be applied as as a
routine screening method.
Microscopic diagnostic curettage:
Invasive surgery, significant pain, has the risk of side effect(e.g. bleeding, infection,
uterine perforation, uterine adhesions etc.), along with the possibility of missed
scratch.
Endometrial biopsy:
Gold standard, invasive surgery, and it is easy to get insufficient and inaccurate
samples, especially for postmenopausal patients
Product performance: endometrial cancer
Combined with the existing clinical
uterine cavity and cervical
exfoliation cell sampling devices -
Pap brush and Tao brush, the noninvasive screening of endometrial
cancer is realized.
Double-blind samples: ① Pap sample（109 ）：NE 47 ，EH 20 ，AH 9 ，EC 33 .
② Tao sample（103 ）：NE 44 ，EH 20 ，AH 8 ，EC 31 .
NE: Normal endometrium
EH: Endometrial hyperplasia
AH: Atypical hyperplasia
EC: Endometrial cancer
Double-blind test results show:
Pap brush: AUC =0.86, specificity=82.81%, sensitivity=80.65%;
Tao brush: AUC=0.83, specificity=95.31%, sensitivity=61.29%;
Summary
Project Application scenarios Sample types Sample volume Transportation
requirement
TAGMe
DNA methylation detection
for female genital tract cancer
-
• Early cancer screening
• Auxiliary diagnosis
• Risk monitoring
• Recrudescence monitoring
Cervical scraping
(TCT sampling method)
2～5 mL Room temperature
Patients
Colposcopy is recommended to detect
for cervical cancer
Test regularly TAGMe DNA methylation detection
positive
Negative
Detection for endometrial
cancer
Negative
Endometrial
cancer
treatment
Positive
Negative
Cervical
cancer
treatment
Positive
Full-process solution for urinary tract
cancer
TAGMe-UrCan
Product performance
Urine detection for bladder cancer
Double-blind validation of urine samples for bladder cancer,
AUC=0.93, specificity = 92.9%, sensitivity = 85.7%;
Product performance
Bladder cancer: 90% of which is transitional epithelial cell carcinoma;
80% of which is non-invasive carcinoma; 93% of which is low-grade carcinoma.
The detection rate of high-grade bladder cancer is 92.8% and
that of low-grade bladder cancer is 82.7%;
The detection rate of invasive carcinoma (MIBC) is 95.9%,
The detection rate for non-invasive carcinoma (NMIBC) is
87.8%.
Product performance
肾盂癌、输尿管癌尿液检测情况
Renal pelvis cancer: sensitivity=91.7%, specificity=92.1%;
Ureteral cancer: sensitivity=78.7%, specificity=92.1%;
Urine detection for renal pelvis cancer and ureteral cancer
Application scenario: Auxiliary diagnosis
Subject Outpatient
service
Diagnosed by
cystoscopy
Surgical
treatment
Negative
Positive
Positive
Positive
Negative & Comprehensive diagnosis of
doctors
Negative
Urine exfoliate cytology/ultrasound/FISH, etc
TAGMe-UrCan
Comprehensive diagnosis of
doctors
TAGMe-UrCan
TAGMe-UrCan
Detection every 1-
3 months
Negative
Application scenario 2: For patients with clinical symptoms such as space-occupying lesions, hematuria, etc., but the cystoscopy comes back negative;
Positive: high risk of cancer, recommend to re-examine for cystoscopy, close monitoring, and follow the doctor's advice;
Negative: low risk of cancer, regular check-up, cancer risk monitoring;
Application scenario 1: Auxiliary diagnosis is
carried out by TAGMe-UrCan for patients with
suspected bladder cancer in outpatient clinics,
inability to do cystoscopy due to urethral
stenosis, suspected upper urothelial carcinoma,
etc.;
Positive: high risk of cancer, recommend to
receive cystoscopy to confirm, or follow the
doctor’s advice;
Negative: low risk of cancer, regular test of
DNA methylation tests, or follow the doctor’s
advice;
Treatment for urothelial carcinoma
Case study of surgical efficacy determination
All patients (12/12) had lower postoperative DNA methylation level than before, but postoperative DNA methylation level of yellow SS was still a strong
positive, suggesting a high suspicion of postoperative tumor residue. It was strongly recommended to review and monitor.
Preoperative and postoperative analysis of urothelial carcinoma
Huang ** Liu ** Liang ** Chen ** Dong ** Zuo ** Sheng ** Zhu ** Xiang ** Zhu ** Cai ** Lu **-
Application scenario: Treatment efficacy assessment
Subject Diagnosed Surgical treatment First perfusion
chemotherapy
Negative
Positive
Positive
Negative
TAGMe-UrCan
detection before
surgery
Negative
N+1th perfusion
chemotherapy
Suspend perfusion
chemotherapy
recrudesce
monitoring
TAGMe-UrCan
detection after
surgery
Evaluate the efficacy based
on changes in methylation
values before and after
surgery
TAGMe-UrCan detection
before the first perfusion
chemotherapy
TAGMe-UrCan
detection after Nth
perfusion chemotherapy
Evaluate the efficacy based
on changes in methylation
values
Application Scenario 3: Evaluation of Surgical Efficacy:
1. Methylation value is still above the threshold (positive) after the surgery: recommend
to carry out perfusion chemotherapy and closely monitor the risk of recrudesce;
2. Methylation value is below the threshold (negative) after the surgery: follow the
doctor’s comprehensive judgements for follow-up treatment plan;
Application scenario 4: Evaluate the efficacy by dynamic changes in
methylation values after each perfusion chemotherapy
1. The postoperative methylation value is still above the threshold
(positive): recommend to continue (or change the regimen) for
perfusion chemotherapy and closely monitor the risk of recrudesce;
2. The postoperative methylation value is below the threshold
(negative): follow the doctor comprehensive judgements on whether
to stop perfusion chemotherapy;
Recrudesce of urinary urothelial carcinoma
Recrudesce monitoring
TAGMe Methylation
detection
Clinical procedures
Outpatie
nt service
Diagnosed
by
cystoscopy
Surgical
treatment
Leave
hospital
TAGMe
detection-1
TAGMe
detection-2
TAGMe
detection-3
Surgical
treatment
TAGMe
detection1
Continue
follow-up
21.01.04
Cystoscopy: highgrade invasive
urothelial
carcinoma with
squamous
metaplasia
Patient: Lu **,
male, 82 years
old
First diagnosis:
malignancy of
the bladder
21.01.19
Surgery:
Transurethral
resection for
bladder cancer
(TURBT)
21.01.18
Before
surgery：
TAGMe
Value = 0.1，
Positive
21.02.18
TAGMeValue =
3.5, negative,
indicating no
recrudesce
21.03.16
TAGMe
Value = 1.8,
positive,
indicating
recrudesce
21.04.19
TAGMe
Value = -0.2,
positive,
indicating
recrudesce
21.05.26
TAGMe
Value = 4.7,
negative,
indicating no
recrudesce
21.05.10
Cystoscopy: 1.5*0.6
cauliflower-like neoplasia is
seen at the lateral margin of
the right ureteral orifice,
indicating recrudesce
Case studies of recrudesce monitoring
Application scenario: Recrudesce monitoring
Outpatient Diagnosed Surgery or other
treatment
Three months
after surgery
Positive Negative
Positive Positive
Negative
Cystoscopy re-examination
Receive TAGMe-UrCan
detection once a month for
the first 3 months after
surgery
Negative
N months after
surgery
Continue recrudesce
monitoring
Receive TAGMe-UrCan
detection before each
cystoscopy after three
months
Application scenario 5: Within 3 months after
surgery, receive TAGMe-UrCan once a month
can dynamically detect the risk of early
postoperative recrudesce
1. Positive: high risk of recrudesce,
recommend to have cystoscopy review early,
and closely monitor;
2. Negative: the risk of recrudesce is low,
follow the doctor's comprehensive judgment
and advice. Application scenario 6: After 3 months of surgery, before each cystoscopy, have TAGMe-UrCan to
detect the risk of recrudesce after surgery for long-term dynamic detection
1. Positive: high risk of recrudesce, recommend to have cystoscopy review early, and closely monitor:
2. Negative: the risk of recrudesce is low, follow the doctor's comprehensive judgment and advice.
Outpatient
service
Diagnosed
by
cystoscopy
Surgical
treatment
Leave
hospital
TAGMe
recrudesce
detection-1
TAGMe
recrudesce
detection-2
Cystoscopic
review
• Sampling tubes are mailed directly to patients. Urine can be taken at home, which is convenient!
• TAGMe can be applied to whole process from early screening, auxiliary diagnosis, efficacy evaluation to
recrudesce monitoring of urinary urothelial cancer.
Changhai Hospital - Full Process Case Study
20.03.31 Cystoscopy:
Cauliflower-like neoplasia
is seen at the ureteral
opening on the left side of
the bladder, and
cauliflower new organism
is seen at the top of the
bladder
Patient: Liu **,
female, 82 years old
Initial diagnosis: highgrade varus papillary
urinary tract
carcinoma of the
bladder
20.05.22 Surgery:
Transurethral
resection for
bladder cancer
(TURBT)
21.01.27 Cystoscopy:
Cauliflower-like neoplasia
on the anterior wall of the
bladder; 21.02.01 Pathology:
High-grade papillary
urothelial carcinoma
20.05.22
Before surgery:
TAGMe Value =
94, positive
20.05.22
After surgery:
TAGMe Value = 42,
negative, indicating
successful surgery
20.12.26
TAGMeValue = 85,
positive, indicating
recrudesce
21.01.26
TAGMeValue = 95,
positive, indicating recrudesce and
progression; doctors strongly recommend
returning to the hospital for reexamination!
20.06~20.12：
Seven months after the operation, due
to the inconvenience of her location,
cystoscopy pain and other reasons, the
patient's compliance was poor, and
she did not return to the hospital for
re-examination
20.03.24
TAGMe Value = 92,
positive, indicating a
high risk of urinary
urothelial cancer
Auxiliary diagnosis Efficacy assessment recrudesce monitoring
Clinical procedures
TAGMe-UrCan
21.01.27 Cystoscopy
Summary of methylation detection for urothelial carcinoma
Sample requirements
Noninvasive: Only 30 ml of urine is required
Convenient: Samples can be taken at home
Simple: Storage and shipping at room temperature for 15 days
Fast: Electronic reports takes only 3 to 5 work days
Scenarios
High-risk populations, early screening
Clinical-suspicious people, assist cystoscopy for diagnosis
Perfusion chemotherapy, efficacy assesment
Initial prognosis, risk assessment of recrudesce
Prognostic recrudesce, long-term recrudesce monitoring
Epiprobe TAGMe DNA methylation molecular detection provides
a full-process solution for urinary tract carcinoma
Subject
After surgery and long-term recrudesce monitoring
Outpatient
service
Diagnosed by
cystoscopy
Surgical
treatment
Positive
Early postoperative
TAGMe-UrCan
TAGMe-UrCan
Negative
Perfusion
chemotherapy
TAGMe-UrCan
TAGMe-UrCan
Long-term
postoperative
TAGMe-UrCan TAGMe-UrCan
Before diagnosis:-Adjunctive diagnosis and recrudesce
monitoring
During treatment. : Evaluation of surgical
efficacy and perfusion therapy efficacy
Appendix : Academic Publications
Academic Publications
Genome Research, 2019.01 (IF=11.1)
Cancer Research, 2019.10 (IF=12.7)
Clinical and Translational Medicine, 2021.06 (IF=11.5)
Frontiers in Molecular Biosciences (IF=5.2)
Signal Transduction and Targeted Therapy（IF=38.104）
Appendix : Introduction
As a high-tech enterprise founded in 2018 by top epigenetic experts, Epiprobe focuses on the molecular diagnosis of
cancer DNA methylation and precision theranostics industry. With a profound technology basis, EPIPROBE aims to lead
the era of new products to nip cancer in the bud!
Based on Epiprobe core team’s long-term research, development and transformation in the field of DNA methylation
with the cutting-edge innovations, combined with the unique DNA methylation targets of tumors, Epiprobe uses a unique
multivariate algorithm combining big data and artificial intelligence technology to independently develop an exclusive
patent-protected liquid biopsy technology. By analyzing the methylation level of specific sites of free DNA fragments in
the sample, the shortcomings of traditional examination methods and the limitations of surgery and puncture sampling
are avoided, which not only achieves accurate detection of early tumors, but also enables real-time monitoring of tumor
occurrence and development dynamics.
Epiprobe’s tumor molecular detection technology can be used for early tumor screening, auxiliary diagnosis,
preoperative and postoperative evaluation, recrudescence monitoring, which runs through the whole process of tumor
diagnosis and treatment, providing better solutions for doctors and patients.
About Epiprobe
Add: 6th Floor, Building 4 , No. 333 Guiping Road, Xuhui District, Shanghai,China
Email: service@epiprobe.com