Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

Katarzyna Ratajczak-Wielgomas,Marzenna Podhorska-Okolow,Jedrzej Grzegrzołka,Konrad Pawelczyk,Katarzyna Nowinska,Piotr Dziegiel,Alicja Kmiecik,Aleksandra Partynska,Agnieszka Gomulkiewicz,Aleksandra Piotrowska

doi:10.3390/ijms21197025

Katarzyna Ratajczak-Wielgomas, Marzenna Podhorska-Okolow + Show 8 more

Open Access

https://doi.org/10.3390/ijms21197025

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Abstract

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

Highlights

Lung cancer remains the leading cancer worldwide with regard to incidence and mortality rates [1,2]
squamous cell carcinoma (SCC) are believed to arise from metaplastic cells in the large airways, and they are most commonly associated with smoking, while ACs are malignant cancers that form glands and papillary structures
The present paper shows that POSTN-positive cancer-associated fibroblasts (CAFs) increased with the histological grade (G) of non-small-cell lung cancer (NSCLC) and achieved their highest value in G3 and their lowest in G1 tumours, both in the whole cohort and in the particular histological subtypes (AC and SCC)

Summary

Introduction

Lung cancer remains the leading cancer worldwide with regard to incidence and mortality rates [1,2]. SCCs are believed to arise from metaplastic cells in the large airways, and they are most commonly associated with smoking, while ACs are malignant cancers that form glands and papillary structures. They are the most common histological type in non-smokers [3,4]. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells.

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