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

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.

Role of Periostin Expression in Non-Small Cell Lung Cancer: Periostin Silencing Inhibits the Migration and Invasion of Lung Cancer Cells via Regulation of MMP-2 Expression

“…Our results confirmed the increased expression of POSTN in cancer cells of NSCLC compared to NMLT, suggesting that POSTN could be related to the process of carcinogenesis in NSCLC. The results of the present study are in line with our previous observations regarding POSTN expression in cancers cells of invasive ductal carcinoma (IDC) [35] as well as in the stromal compartment (CAFs) of NSCLC [24]. Moreover, LCM, which was used to determine the POSTN mRNA expression levels in NSCLC cancer cells, confirmed the TMA IHC observations.…”

“…The correlation analysis showed a strong positive significant (r = 0.7085, **** p < 0.0001) correlation of POSTN expression in the cytoplasm of cancer cells with POSTN expression in tumor stromal cells (CAFs) in the whole cohort (Figure 5A). The results of POSTN expression in the stromal cells (CAFs) were used from previously conducted and published studies [24]. Furthermore, we also noticed a strong positive significant correlation between epithelial POSTN expression and the level of POSTN expression in stromal cells in AC and SCC subtypes (r = 0.7897, r = 0.6607, **** p < 0.0001, respectively) (Figure 5B,C).…”

“…POSTN upregulation has been demonstrated for many cancer types, such as non-small cell lung cancer (NSCLC) [24,26], invasive ductal breast cancer (IDC) [27], pancreatic [28], and ovarian cancer [29], and is consequently defined as a tumor-enhancing factor [17]. Only a few reports in bladder cancer and osteosarcoma have shown POSTN as a tumor-inhibiting factor [21,30].…”

mRNA expression level of CDH2, LEP, POSTN, TIMP1 and VEGFC modulates 5‑fluorouracil resistance in colon cancer cells

“…A recent study reported that TIMP1 knockdown using short hairpin RNA in gemcitabine (GEM)-resistant pancreatic ductal adenocarcinoma cells enhanced GEM sensitivity and reversed chemoresistance by inducing cell apoptosis ( 39 ). POSTN expresses extracellular matrix periostin, which is involved in the activation of the PI3K/Akt signaling pathway ( 40 , 41 ) and was found to be an independent negative prognostic factor in non-small cell lung carcinoma ( 42 ). In addition, POSTN protein expression has been confirmed to be positively associated with cancer drug resistance ( 43 ).…”

Diagnostic value of periostin in lung cancer‐related malignant pleural effusion

“…The tumor microenvironment (TME) is a special environment for tumor proliferation that is composed of tumor cells, endothelial cells, tumor stromal cells, ECM, and various factors 28 . POSTN, as an ECM protein, is highly expressed in the stromal cells around the cancer epithelium, 29 promoting the occurrence, metastasis, and progression of tumors by establishing and remodeling the TME 30 . POSTN can induce epithelial–mesenchymal transition in lung cancer by activating the p38/ERK pathway and inhibiting the expression of microRNA‐381 that targets both Snail and Twist 31 .…”