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Moreover, the incidence and mortality rates are strongly associated with the geographical position and thus also with culture, diet, and economic development of the region. GC two-fold more frequently affects men than women. The above data indicate that most of the diagnosed cases are in advanced stages. Although the GC incidence decreased in the last decades, the mortality is as much as 8.2% of all cancer deaths and the general five-year survival rate is approximately 28%. Gastric cancer (GC) is the fifth most common malignant neoplasm and simultaneously the third leading cause of cancer death worldwide. Keywords: GDF15, GFRAL, RET, gastric cancer, prognostic factor Introduction
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If validated in large-scale studies, the individual and combined expression of GDF15, GFRAL and RET may provide significant clinical implications for the prognosis prediction of GC patients. Furthermore, high combined expression of the three markers: GDF15+GFRAL+RET was significantly associated with reduced OS, and it was an independent prognostic factor of borderline significance in terms of OS, when adjusted for covariates. Specifically, GFRAL and RET emerged as independent prognostic factors associated with poor OS. Through in silico data analysis, we showed that high GDF15 expression was associated with better overall survival (OS) of GC patients, whereas the opposite was true for high levels of GFRAL or RET. No other relationships between the expression status of the examined proteins and clinicopathological characteristics of GC patients were found. We found that the protein expression of GDF15, GFRAL and RET was significantly elevated and positively correlated in our set of GC tissues, which was reflected in their tendency to be overexpressed in low-grade and intermediate-grade tumors rather than high-grade ones. Protein expression was examined by immunohistochemistry on tissue microarrays containing 104 and 30 consecutive GC and normal gastric mucosa samples, whereas gene expression data for The Cancer Genome Atlas cohort of 413 GC patients were obtained from public sources.
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Therefore, we aimed to analyze the expression levels of GDF15, GFRAL and RET in GC tissues in relation to each other and clinicopathological features, including patient survival, in order to establish a potential implication of the body-weight signaling pathway in the pathology and clinical outcome of GC. The existence, the functional role and clinical relevance of GDF15 and its signaling through a GFRAL/RET-dependent complex in gastric cancer (GC) and other human tumors remain to be elucidated, despite the widespread recognition of obesity as an important cancer-predisposing factor. Select the file that you have just downloaded and select import option Reference Manager (RIS).
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Moreīuchholz K, Antosik P, Grzanka D, Gagat M, Smolińska M, Grzanka A, Gzil A, Kasperska A, Klimaszewska-Wiśniewska A. Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Department of Clinical Pathomorphology, 9 Maria Skłodowska Curie St. ✉ Corresponding author: Anna Klimaszewska-Wiśniewska, Ph.D. Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland. Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.Ģ. Karolina Buchholz 1,2*, Paulina Antosik 1*, Dariusz Grzanka 1, Maciej Gagat 2, Marta Smolińska 1, Alina Grzanka 2, Arkadiusz Gzil 1, Anna Kasperska 1, Anna Klimaszewska-Wiśniewska 1ġ. Research Paper Expression of the Body-Weight Signaling Players: GDF15, GFRAL and RET and their clinical relevance in Gastric Cancer