Dataset Information

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

ABSTRACT:

Background

Fibroblast-activating protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) in many human carcinomas and in some types of carcinoma cells. Here, we examined the proportion of FAP protein expression in non-small cell lung carcinoma (NSCLC) and investigated the correlation of FAP expression with clinicopathological background.

Methods

In total, 344 NSCLC tissues were examined. Tissue microarrays were constructed, and FAP expression was analyzed using immunohistochemistry. The status of FAP expression in tumor cells and CAFs was correlated with clinicopathological background, molecular features, and patient outcomes.

Results

A total of 280 patients (81.4%) had low FAP expression, and 64 patients (18.6%) had high FAP expression in tumor cells. In CAFs, 230 patients (66.9%) had low FAP expression, and 114 patients (33.1%) had high FAP expression. In multivariate analyses, high FAP expression in tumor cells was an independent predictive factor of both overall survival (OS; hazard ratio [HR] = 2.57, 95% confidence interval [CI]: 1.49-4.42, p < 0.001) and recurrence-free survival (RFS; HR = 2.13, 95% CI: 1.38-3.29, p < 0.001). Based on combinations of FAP expression in tumor cells and CAFs, patients with Low^T /Low^CAFs had better OS and RFS than did those in the other subgroups. By contrast, patients with High^T /High^CAFs had poor OS and RFS compared with those in the other subgroups.

Conclusions

Overall, FAP expression in tumor cells and the combination FAP expression in tumor cells and CAFs were strongly associated with patient survival and may be useful predictive biomarkers for patient outcomes in NSCLC.

SUBMITTER: Yanagawa N

PROVIDER: S-EPMC9376177 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

Yanagawa Naoki N Sugai Mayu M Shikanai Shunsuke S Sugimoto Ryo R Osakabe Mitsumasa M Uesugi Noriyuki N Saito Hajime H Maemondo Makoto M Sugai Tamotsu T

Thoracic cancer 20220711 16

<h4>Background</h4>Fibroblast-activating protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) in many human carcinomas and in some types of carcinoma cells. Here, we examined the proportion of FAP protein expression in non-small cell lung carcinoma (NSCLC) and investigated the correlation of FAP expression with clinicopathological background.<h4>Methods</h4>In total, 344 NSCLC tissues were examined. Tissue microarrays were constructed, and FAP expression was analyzed using immunohi ...[more]

PMID: 35818720

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Project description:BackgroundUbiquitin Carboxyl-Terminal Hydrolase-L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed throughout the central and peripheral nervous system and in cells of the diffuse neuroendocrine system. Aberrant function of UCH-L1 has been associated with neurological disorders such as Parkinson's disease and Alzheimer's disease. Moreover, UCH-L1 exhibits a variable expression pattern in cancer, acting either as a tumour suppressor or promoter, depending on the type of cancer. In non-small cell lung carcinoma primary tumour samples, UCH-L1 is highly expressed and is associated with an advanced tumour stage. This suggests UCH-L1 may be involved in oncogenic transformation and tumour invasion in NSCLC. However, the functional significance of UCH-L1 in the progression of NSCLC is unclear. The aim of this study was to investigate the role of UCH-L1 using NSCLC cell line models and to determine if it is clinically relevant as a prognostic marker for advanced stage disease.MethodsUCH-L1 expression in NSCLC cell lines H838 and H157 was modulated by siRNA-knockdown, and the phenotypic changes were assessed by flow cytometry, haematoxylin & eosin (H&E) staining and poly (ADP-ribose) polymerase (PARP) cleavage. Metastatic potential was measured by the presence of phosphorylated myosin light chain (MLC2). Tumour microarrays were examined immunohistochemically for UCH-L1 expression. Kaplan-Meier curves were generated using UCH-L1 expression levels and patient survival data extracted from Gene Expression Omnibus data files.ResultsExpression of UCH-L1 was decreased by siRNA in both cell lines, resulting in increased cell death in H838 adenocarcinoma cells but not in the H157 squamous cell line. However, metastatic potential was reduced in H157 cells. Immunohistochemical staining of UCH-L1 in patient tumours confirmed it was preferentially expressed in squamous cell carcinoma rather than adenocarcinoma. However the Kaplan-Meier curves generated showed no correlation between UCH-L1 expression levels and patient outcome.ConclusionsAlthough UCH-L1 appears to be involved in carcinogenic processes in NSCLC cell lines, the absence of correlation with patient survival indicates that caution is required in the use of UCH-L1 as a potential prognostic marker for advanced stage and metastasis in lung carcinoma.

Dataset Information

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

Background

Methods

Results

Conclusions

Publications

High expression of fibroblast-activating protein is a prognostic marker in non-small cell lung carcinoma.

Similar Datasets

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