Periostin and tumor-stroma interactions in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-associated mortality globally. Interactions of the cancer cells with the tumor microenvironment are essential carcinogenic features for the majority of solid tumors, such as pancreatic cancer. The present study investigated the role of stromal activation in NSCLC and analyzed the surgical specimens of 93 patients by immunohistochemistry with regard to periostin (an extracellular matrix protein), α-smooth muscle actin (α-SMA; a marker of myofibroblasts) and cluster of differentiation 31 (CD31; a marker of endothelial cells), and the activated stroma index. There was a trend towards reduced overall survival for patients with high periostin expression (hazard ratio, 1.80; 95% confidence interval, 0.99–3.27; P=0.050). No significant correlations with overall survival were identified for α-SMA (P=0.930), CD31 (P=0.923), collagen (P=0.441) or the activated stroma index (P=0.706). In a multivariable analysis, the histological tumor subtype, tumor stage, lymph node involvement and resection status were independent prognostic factors in NSCLC, but none of the investigated immunohistochemical markers were prognostic factors. Thus, the tumor microenvironment and stroma activation did not prove to be of prognostic relevance for lung cancer, as it has been previously described for pancreatic cancer. Other markers of the microenvironment of NSCLC may be of higher prognostic value, pointing towards tumor-type specific effects.

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

“…Our studies are in line with the results obtained by Okazaki et al [ 7 ], Hong et al [ 27 ], Soltermann et al [ 32 ], and Takanami et al [ 42 ], who also indicated that increased POSTN expression was associated with a shorter survival of patients with NSCLC. Our results were also in agreement with the previously established fact that the primary, important prognostic factors in patients with NSCLC are disease stagings (TNM, pT, and pN) [ 6 , 10 ]. It should be emphasized that our research has been the first to show a relationship between high POSTN expression in CAFs and a significantly shorter OS on a large population of patients with NSCLC as well as in two histological subtypes (AC and SCC).…”

“…The present paper also shows that POSTN-positive CAFs increased with the histological grade (G) of 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). Similar results were reported in NSCLC by Nitsche et al [ 6 ] and Murakami et al [ 10 ], although they included a significantly smaller pool of lung cancer cases and no SCC or AC cases. Furthermore, as observed in other cancers [ 30 , 34 , 35 , 39 ], an increased expression of POSTN was also significantly associated with clinical stage, regional lymph node (N) metastasis, and the primary tumour (T) stage, suggesting that POSTN secreted by CAFs could be a key element in the progression of NSCLC.…”

“…The majority of patients are diagnosed at an advanced tumour stage and therefore are not candidates for curative surgical resection. These patients receive multimodal chemotherapy, with or without radiotherapy [ 5 , 6 ]. Although the prognosis for NSCLC has improved, new prognostic markers and therapeutic strategies are still needed [ 7 ].…”

“…Growing evidence has implicated that POSTN is overexpressed in various types of human cancer tissues, including ovarian cancer [ 21 ], breast cancer [ 22 , 23 ], colon cancer [ 24 ], head and neck cancer [ 25 ], and pancreatic ductal adenocarcinoma [ 26 ]. However, the effect of POSTN expression in CAFs on the progression of NSCLC remains largely unknown despite some published reports related to NSCLC [ 6 , 7 , 27 ]. In addition, the expression and function of POSTN in stromal cells (CAFs) in NSCLC have not been sufficiently studied, especially in respect to two distinctive histological groups, i.e., squamous cell cancer (SCC) and adenocarcinoma (AC).…”

Periostin function in communication with extracellular matrices

“…Pathologically, periostin has also been localized in infarcted myocardium Oka et al 2007), fibrosis (Okamoto et al 2011;Ishikawa et al 2014;Naik et al 2012;Takayama et al 2006;Uchida et al 2012), tissues undergoing wound healing (Nishiyama et al 2011;Norris et al 2007;Ontsuka et al 2012;Zhou et al 2010), and cancer-associated stroma (Fukushima et al 2008;Kashima et al 2009;Kikuchi et al 2008Kikuchi et al , 2014Liu et al 2014;Nitsche et al 2016;Oskarsson and Massague 2012;Qin et al 2016;Ruan et al 2009;Sung et al 2016;Tian et al 2015;Underwood et al 2015;Wang and Ouyang 2012). Taken together, periostin expression is well correlated with tissue regeneration (Conway et al 2014).…”