Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05502458 |
Other study ID # |
2020-09-01 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 1, 2020 |
Est. completion date |
August 8, 2022 |
Study information
Verified date |
August 2022 |
Source |
Zhejiang Cancer Hospital |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
To investigate the effects of perioperative anesthetic drugs propofol and desflurane on
circulating tumor nucleic acids (CK7, ELF3, EGFR and EphB4 mRNA) in the blood of patients
with liver cancer, so as to provide scientific reference for clinical anesthesia in the
perioperative treatment of tumor
Description:
Hepatocellular carcinoma (HCC) is one of the most malignant tumors in oncology. Its incidence
is increasing, and there is a lack of reliable biomarkers for early diagnosis, prognosis
evaluation and efficacy evaluation. There is a pool of tumor molecules derived from primary
tumors in the blood circulation, including Circulating tumor proteins, Circulating tumor
cells (CTCs), Extracellular vesicles, Evs, Tumor "educated" platelets (TEPs), and Circulating
Tumor nucleic acids, known as Circulating Tumor DNA, CtDNA is a Circulating cell-free DNA
(ccfDNA). Liquid biopsy is performed to detect tumor molecules from blood circulation. Small
RNA (miRNA) and long noncoding RNA (miRNA) in liquid biopsy are detected. Circulating tumor
RNA (ctRNA), such as lncRNA, can be used as epigenetic biomarkers to improve the early
diagnosis of HCC and to treat patients with early and advanced HCC. Propofol and desflurane,
as important anesthesia drugs in perioperative period, have been shown to affect the
concentration of circulating nucleic acid in patients. Furong Song found that propofol could
inhibit the overexpression of HOXA11-AS, which reversed the inhibitory effect of propofol
treatment on HCC cell progression, by promoting the expression of Mir-4458, and had an impact
on HCC cell progression . However, Dongmei Wang and their colleagues found that circulating
H19 inhibited the effect of propofol in promoting HCC cell apoptosis by upregulating LIMK1
(LIM domain kinase 1) through spongy Mir-520a-3p . Meanwhile, Buschmann and his team found
that propofol and desflurane inhibited key cancer-related pathways such as proliferation and
migration in colorectal cancer, and found that propofol did not affect the size distribution
and protein labeling of circulating vesicles, but could reduce their concentration . Compared
with inhaled anesthetics, Bon-Wook Koo found that HCC patients treated with propofol had a
lower recurrence rate and a longer average recurrence time than those treated with inhaled
anesthetics . Hou-chuan Lai found that compared with desflurane anesthesia regimen, propofol
anesthesia regimen significantly improved the survival rate of patients with liver cancer
without distant metastasis or local recurrence . Meanwhile, Frederique Hovaguimian found that
in nonmetastatic and metastatic breast cancer, the maximum number of circulating tumor cells
increased by 36% after sevoflurane inhalation anesthesia and was independently associated
with a higher risk of disease recurrence and reduced survival . At this time, the monitoring
of circulating tumor cells can represent promising methods, such as the detection of suitable
markers of circulating tumor cells, such as Cytokeratin 7 (CK7), E74-like factor 3 (ELF3),
Epidermal growth factor receptor (EGFR) and Peripheral blood mononuclear cells, The
expression of erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) mRNA in
PMBCs, In order to better understand the effect of anesthesia on perioperative tumor
treatment, this evidence has been supported by domestic and foreign studies . Soo-ho Lee and
his colleagues found that CK7-negative liver cancer patients had a higher survival rate than
all positive patients [9], which was supported by Xialing Huang and his team . Longbo Zheng
found that ELF3 inhibits ZE1 by inhibiting Mir-141-3p, thereby inhibiting E-cadherin in HCC
cells and promoting EMT, which is a potential prognostic biomarker and/or therapeutic target
for HCC . Zhe Wu found that lncrNA-UBE2R2-AS1 in HCC shows carcinogenic effect through the
up-regulation of EGFR by Mir-302b, and can be used as a potential therapeutic target and
prognostic biomarker for HCC patients , and this mechanism of action was confirmed by
Zhen-Jiang Ma and his research . At the same time, it was found that the expression level of
EphB4 was increased in HCC tumor tissues, and the levels of EphB4 and P-JAK2 were positively
correlated in samples of HCC patients , while the expression of CIRC-EPHB4 was
down-regulated. Circ-ephb4 overexpression inhibited the viability of HCC cells, induced
apoptosis, and inhibited cell migration and invasion by inhibiting the expression of
hypoxia-inducible factor-1α (HIF-1α) . However, the perioperative effects and molecular
mechanisms of propofol and desflurane on circulating tumor nucleic acids in liver cancer are
not very clear at present, and further relevant studies are needed to clarify, so as to
provide support and guidance for the development of perioperative anesthesia plan and
clinical diagnosis of liver cancer.