Dataset Information

The prognostic value of the lysyl oxidase family in ovarian cancer.

ABSTRACT:

Background

Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase-like genes (LOXL1-4), in ovarian cancer (OC) patients.

Material and methods

The Kaplan-Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression-free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were also analyzed according to various clinicopathological characteristics, including histological subtypes, clinical stages, pathological grades, and chemotherapeutic treatments.

Results

Overexpression of LOX, LOXL1, LOXL2, and LOXL3 mRNA indicated poor OS and PFS in OC patients, particularly in serous and grade II + III OC patients. Overexpression of LOXL4 mRNA resulted in worse PFS in OC patients. Overexpression of LOX and LOXL1 mRNA showed worse OS and PFS in stage III + IV OC patients, and overexpression of LOXL3 mRNA indicated worse OS and PFS in stage I + II OC patients. Overexpression of LOX, LOXL3, and LOXL4 mRNA indicated worse OS and PFS among OC patients who received platinum, taxol, and taxol + platinum chemotherapy. Overexpression of LOXL1 and LOXL2 mRNA was related to lower OS and PFS in OC patients who received platinum chemotherapy.

Conclusion

LOX, LOXL1, LOXL2, and LOXL3 may become potential predictive markers for negative outcomes in OC patients. Moreover, the LOX family can serve as new molecular predictors for the efficiency of platinum-based chemotherapy in OC patients.

SUBMITTER: Ye M

PROVIDER: S-EPMC7755792 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

The prognostic value of the lysyl oxidase family in ovarian cancer.

Ye Miaomiao M Zhou Junhan J Gao Ying Y Pan Shuya S Zhu Xueqiong X

Journal of clinical laboratory analysis 20201015 12

<h4>Background</h4>Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase-like genes (LOXL1-4), in ovarian cancer (OC) patients.<h4>Material and methods</h4>The Kaplan-Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression-free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were a ...[more]

PMID: 33058284

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Project description:Lysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer.Gene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 ((18)F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of ?-aminopropionitrile (BAPN), an irreversible inhibitor of LOX.Immunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-NH2, was found to be localized in different cellular compartments under these conditions. After injection of [(18)F]fluorobenzoate-GGGDPKGGGGG-NH2, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer.The present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer.

Dataset Information

The prognostic value of the lysyl oxidase family in ovarian cancer.

Background

Material and methods

Results

Conclusion

Publications

The prognostic value of the lysyl oxidase family in ovarian cancer.

Similar Datasets

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