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Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

ABSTRACT: BACKGROUND:S100A13 plays a key role in tumor growth and metastasis. The purpose of this study was to investigate the prognostic significance of S100A13 expression, microvessel density (MVD), and survival in early stage non-small cell lung cancer (NSCLC). METHODS:In silico analysis was performed to determine the associations between S100A13 and NSCLC. The data of 82 patients with early-stage NSCLC who underwent radical resection were evaluated. Paraffin-embedded tumor specimens were stained with S100A13 and CD31 (a specific endothelial marker) using immunohistochemical methods. Prognostic significance was assessed by univariate and multivariate analyses. RESULTS:S100A13 messenger RNA was overexpressed in NSCLC, especially in advanced stage. Of the 82 NSCLC specimens examined, 37 (45.1%) cases exhibited S100A13 overexpression and 31 (37.8%) showed high MVD. Univariate analysis indicated that gender, age, smoking status, histology type, tumor differentiation, and T stage were not significantly associated with prognosis. However, the overall and disease-free survival rates of patients with S100A13 overexpression and high MVD were significantly lower than in the remaining cases. Multivariate analysis demonstrated that only S100A13 overexpression was an independent factor for poor prognosis in early-stage NSCLC. Statistical analysis demonstrated that the MVD was significantly higher in tumors with high (67.6%, 25/37) compared to low S100A13 expression (13.3%, 6/45) (P?

SUBMITTER: Miao S

PROVIDER: S-EPMC6119616 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

Miao Shuncheng S Qiu Tong T Zhao Yandong Y Wang Hongmei H Sun Xiao X Wang YuanYong Y Xuan Yunpeng Y Qin Yi Y Jiao Wenjie W

Thoracic cancer 20180726 9

<h4>Background</h4>S100A13 plays a key role in tumor growth and metastasis. The purpose of this study was to investigate the prognostic significance of S100A13 expression, microvessel density (MVD), and survival in early stage non-small cell lung cancer (NSCLC).<h4>Methods</h4>In silico analysis was performed to determine the associations between S100A13 and NSCLC. The data of 82 patients with early-stage NSCLC who underwent radical resection were evaluated. Paraffin-embedded tumor specimens wer ...[more]

PMID: 30047626

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Project description:BACKGROUND:Accurate survival stratification in early-stage non-small cell lung cancer (NSCLC) could inform the use of adjuvant therapy. We developed a clinically implementable mortality risk score incorporating distinct tumor microenvironmental gene expression signatures and clinical variables. METHODS:Gene expression profiles from 1106 nonsquamous NSCLCs were used for generation and internal validation of a nine-gene molecular prognostic index (MPI). A quantitative polymerase chain reaction (qPCR) assay was developed and validated on an independent cohort of formalin-fixed paraffin-embedded (FFPE) tissues (n = 98). A prognostic score using clinical variables was generated using Surveillance, Epidemiology, and End Results data and combined with the MPI. All statistical tests for survival were two-sided. RESULTS:The MPI stratified stage I patients into prognostic categories in three microarray and one FFPE qPCR validation cohorts (HR = 2.99, 95% CI = 1.55 to 5.76, P < .001 in stage IA patients of the largest microarray validation cohort; HR = 3.95, 95% CI = 1.24 to 12.64, P = .01 in stage IA of the qPCR cohort). Prognostic genes were expressed in distinct tumor cell subpopulations, and genes implicated in proliferation and stem cells portended poor outcomes, while genes involved in normal lung differentiation and immune infiltration were associated with superior survival. Integrating the MPI with clinical variables conferred greatest prognostic power (HR = 3.43, 95% CI = 2.18 to 5.39, P < .001 in stage I patients of the largest microarray cohort; HR = 3.99, 95% CI = 1.67 to 9.56, P < .001 in stage I patients of the qPCR cohort). Finally, the MPI was prognostic irrespective of somatic alterations in EGFR, KRAS, TP53, and ALK. CONCLUSION:The MPI incorporates genes expressed in the tumor and its microenvironment and can be implemented clinically using qPCR assays on FFPE tissues. A composite model integrating the MPI with clinical variables provides the most accurate risk stratification.

Dataset Information

Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

Publications

Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

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