Abstract
A survey on the detection of HPD-related genes by liquid biopsy in patients with lung cancer in China.
Author
person
Peng Zhang
Tianjin Medical University General Hospital, Tianjin, China
info_outline
Peng Zhang, Bo Peng, Zhang Jing, Shaochen Cheng
Full text
Authors
person
Peng Zhang
Tianjin Medical University General Hospital, Tianjin, China
info_outline
Peng Zhang, Bo Peng, Zhang Jing, Shaochen Cheng
Organizations
Tianjin Medical University General Hospital, Tianjin, China, HaploX Biotechnology, Shenzhen, China, HaploX Biotechnology Co. Ltd., Shenzhen, China
Abstract Disclosures
Research Funding
No funding received
None.
Background:
he prognosis for lung cancer patients receiving immunotherapy is impacted by hyper-progression disease (HPD). Assays for HPD-associated gene mutations were anticipated to be crucial for immunotherapy. Although easy and non-invasive, the liquid biopsy technique is not widely employed in immunotherapy. Here, we want to study details of HPD-related gene mutations in the detection of tissue and liquid biopsy and dig out some relevant information from Chinese Lung Cancer (CLC) patients.
Methods:
10 genes with HPD-associated mutation were collected by literature, like SNV (
EGFR
,
KEAP1
,
STK11
,
DNMT3A
,
PTEN
), CNV (
ALK
fusion, amplification of
MDM2
,
MDM4
,
FGF3
,
FGF4
). 3540 cell-free DNA (cfDNA) samples and 6553 tumor tissue samples of LC patients download from Haplab database (HaploX, Shenzhen, China). Genetic alterations were sequenced by NGS platform and microsatellite instability status was calculated through msisensor analysis. The chi-square test was used for statistical hypothesis test.
Results:
In general, all mutation genes tested except
EGFR
were detected significantly differently between tissue and cfDNA samples (p < 0.05). 193 samples (156 tDNA, 37cfDNA) with microsatellite instability (MSI) were screened to test HPD-related gene consistency. Results showed no significant difference in 10 HPD-related genes between MSI tissue and blood samples (p > 0.05). Microsatellite stable (MSS) samples of 4499 tumor DNA and 1173 cfDNA were also performed on consistency test.
EGFR
and the other 4 genes (
FGF3
,
FGF4
,
KEAP1
,
PTEN
) were found consistency in tDNA and cfDNA, and
ALK
(p 0.0051),
MDM2
(p 0.0004),
MDM4
(p 0.0052),
STK11
(p 0.0344),
DNMT3A
(p < 0.0001) showed significant difference of two type of samples.
Conclusions:
In overall samples and subtypes tested, only
EGFR
had no significant differences between tissue and cfDNA, which might make
EGFR
a perfect biomarker candidate in HPD detection and prognosis. Our outcomes also proved that liquid biopsy has some limitations in monitoring HPD-related genes of CLC compared with tissue biopsy. MSS patients presented more reliable results than MSI patients. When monitoring HPD-related genes except for
EGFR
using cfDNA, appropriate patients should be considered.
3 organizations
10 drugs
10 targets
Organization
HaploX Biotechnology, Shenzhen, ChinaOrganization
HaploX Biotechnology Co. Ltd.Drug
MelphalanDrug
NavtemadlinDrug
MDM4Drug
FGF3Drug
FGF4Drug
KEAP1Drug
PTENDrug
STK11Drug
DNMT3ATarget
MDM2Target
MDM4Target
ALKTarget
FGF3Target
PTENTarget
DNMT3ATarget
KEAP1Target
FGF4Target
STK11