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Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.
- Source :
-
Scientific reports [Sci Rep] 2021 Mar 18; Vol. 11 (1), pp. 6255. Date of Electronic Publication: 2021 Mar 18. - Publication Year :
- 2021
-
Abstract
- Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Carcinoma, Hepatocellular pathology
Cell Proliferation drug effects
Cell Proliferation genetics
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms pathology
Male
MicroRNAs genetics
Middle Aged
Nuclear Proteins genetics
Stomach Neoplasms pathology
Transfection
Up-Regulation genetics
Antineoplastic Agents therapeutic use
Carcinoma, Hepatocellular blood
Carcinoma, Hepatocellular drug therapy
Cisplatin therapeutic use
Drug Resistance, Neoplasm genetics
Liver Neoplasms blood
Liver Neoplasms drug therapy
Nuclear Proteins blood
Stomach Neoplasms blood
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33737617
- Full Text :
- https://doi.org/10.1038/s41598-021-85498-7