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. 2023 Feb;28(2):229-239.
doi: 10.1007/s10147-022-02271-0. Epub 2022 Nov 14.

Prognostic impact of tumor microenvironment-related markers in patients with adenocarcinoma of the lung

Mayu Sugai  1   2 , Naoki Yanagawa  1 , Shunsuke Shikanai  1 , Mitsumasa Osakabe  1 , Makoto Maemondo  2 , Hajime Saito  3 , Tamotsu Sugai  4
Affiliations

Prognostic impact of tumor microenvironment-related markers in patients with adenocarcinoma of the lung

Mayu Sugai et al. Int J Clin Oncol. 2023 Feb.

Abstract

Cancer-associated fibroblasts (CAFs) are a prominent component in the tumor microenvironment (TME), which plays an important role in lung carcinogenesis. Here, we investigated microenvironmental markers expressed by CAFs, including α-smooth muscle actin, CD10, podoplanin, fibroblast-specific protein 1, platelet-derived growth factor α and β, fibroblast-associated protein, tenascin-C, zinc finger E-box binding homeobox 1 (ZEB1), and twist-related protein 1 expression levels. We evaluated samples from 257 patients with lung adenocarcinoma (LAD) to assess the associations of CAF-related protein expression patterns with prognosis. LAD cases were stratified using cluster analysis. To determine the utility of prognostic markers in LAD, univariate and multivariate analyses were performed. LAD cases were classified into subgroups 1 and 2. Subgroup 2 was shown to be significantly correlated with disease-free and overall survival using univariate and multivariate analyses in this group. Upregulation of podoplanin was identified as a single prognostic marker in this study by univariate and multivariate analyses. In addition, ZEB1 overexpression was correlated with disease-free survival. Our current results suggested that the specific CAF phenotype (e.g., the expression pattern of CAF-related proteins) could predict outcomes in patients with LAD. In addition, podoplanin upregulation may predict outcomes in these patients.

Keywords: Cancer-associated fibroblast; Immunohistochemistry; Lung adenocarcinoma; Podoplanin; ZEB1.

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Conflict of interest statement

We declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Representative features of immunohistochemical staining of the biological markers examined in this study based on expression score. a α-SMA. b FAP. c Tenascin-C. d Podoplanin. e CD10. (f) PDGFR-α. g PDGFR-β. h FSP1. i ZEB1. j TWIST1. Magnification: × 200
Fig. 2
Fig. 2
Hierarchical cluster analysis of patients with lung adenocarcinoma based on the expression patterns of cancer cells and cancer-associated fibroblast (CAF)-related proteins. The examined lung adenocarcinomas were subclassified into 2 subgroups.
Fig. 3
Fig. 3
Expression level of each marker in lung adenocarcinoma. a α-SMA. b FAP. c Tenascin-C. d Podoplanin. e CD10. f PDGFR-α. g PDGFR-β. h FSP1. i ZEB1. j TWIST1. *, p =  < 0.0001; †, p = 0.0004; ‡, p = 0.0006; §, p = 0.0186
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