Increased Serum Levels of KiSS1-derived Peptides in Non-small Cell Lung Cancer Patient Liquid Biopsies and Biological Relevance

Overview

Journal Transl Lung Cancer Res

Date 2022 Aug 12

PMID 35958339

Authors

Laura Gatti

Luigi Rolli

Cristina Corno

Nives Carenini

Elisabetta Corna

Emilio Ciusani

Simona Frigerio

Simona Pogliani

Carmela Guarino

Ferdinando Ravagnani

Ugo Pastorino

Gabriella Sozzi

Alessandra Macciotta

Paolo Verderio

Chiara M Ciniselli

Paola Perego

Affiliations

Soon will be listed here.

Abstract

Background: The secreted products of the metastasis suppressor gene may represent useful biomarkers in non-small cell lung cancer (NSCLC) but their levels in patients have remained poorly investigated. We previously found that forced expression of decreased the invasive capability of NSCLC drug-resistant cells and a pro-apoptotic role for KiSS1 has been proposed in head and neck cancer. Thus, we designed a translational investigation including a pilot study to analyze KiSS1 levels in liquid biopsies, and experiments to explore the biological relevance of KiSS1 modulation.

Methods: KiSS1-derived peptide levels in liquid biopsies from 60 NSCLC patients were assayed by ELISA. Preclinical experiments were carried out using quantitative real time polymerase chain reaction (qRT-PCR), ELISA, annexin V-binding and caspase activation assays.

Results: We compared KiSS1 release in 3 different matrices (serum, plasma and urine) and the highest levels were detectable in serum (range, 0-4.5 ng/mL). We observed increased levels of seric KiSS1 in NSCLC patients as compared to healthy donors. KiSS1 serum concentrations, after surgical procedure and/or adjuvant therapy. We observed differences among disease stages in urine samples. In preclinical models, mRNA levels were increased by short term exposure to azacytidine, enhanced KiSS1 release was induced by the combination of azacytidine and cisplatin and KiSS1-derived peptides enhanced cisplatin-induced apoptosis. KiSS1 increase was observed upon exposure neurons-enriched cultures to tumor cell conditioned medium.

Conclusions: Our results showing a peculiar modulation of KiSS1 levels in liquid biopsies of NSCLC patients and a regulation of cisplatin-induced apoptosis by KiSS1-derived peptides support an involvement of KiSS1 in cell response to treatment and highlight its promising features as a potential biomarker in NSCLC.

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