Title: |
Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients |
Authors: |
Markus Eckstein, Verena Lieb, Rudolf Jung, Danijel Sikic, Katrin Weigelt, Robert Stöhr, Carol Geppert, Veronika Weyerer, Simone Bertz, Ginette Serrero, Binbin Yue, Arndt Hartmann, Bernd Wullich, Helge Taubert, Sven Wach |
Source: |
Cells, Vol 10, Iss 7, p 1796 (2021) |
Publisher Information: |
MDPI AG, 2021. |
Publication Year: |
2021 |
Collection: |
LCC:Cytology |
Subject Terms: |
GP88, bladder cancer, prognosis, tumor cells, immune cells, lymph node stage, Cytology, QH573-671 |
More Details: |
Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa. |
Document Type: |
article |
File Description: |
electronic resource |
Language: |
English |
ISSN: |
2073-4409 |
Relation: |
https://www.mdpi.com/2073-4409/10/7/1796; https://doaj.org/toc/2073-4409 |
DOI: |
10.3390/cells10071796 |
Access URL: |
https://doaj.org/article/58e242a098ee456492625b9878ffe193 |
Accession Number: |
edsdoj.58e242a098ee456492625b9878ffe193 |
Database: |
Directory of Open Access Journals |
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