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dc.contributor.authorRot, Swetlana-
dc.contributor.authorTaubert, Helge-
dc.contributor.authorBache, Matthias-
dc.contributor.authorGreither, Thomas-
dc.contributor.authorWürl, Peter-
dc.contributor.authorHolzhausen, Hans-Jürgen-
dc.contributor.authorEckert, Alexander W.-
dc.contributor.authorVordermark, Dirk-
dc.contributor.authorKappler, Matthias-
dc.description.abstractIn various tumors, the hypoxia inducible factor-1α (HIF-1α) and the epidermal growth factor-receptor (EGFR) have an impact on survival. Nevertheless, the prognostic impact of both markers for soft tissue sarcoma (STS) is not well studied. We examined 114 frozen tumor samples from adult soft tissue sarcoma patients and 19 frozen normal tissue samples. The mRNA levels of HIF-1α, EGFR, and the reference gene hypoxanthine phosphoribosyltransferase (HPRT) were quantified using a multiplex qPCR technique. In addition, levels of EGFR or HIF-1α protein were determined from 74 corresponding protein samples using ELISA techniques. Our analysis showed that a low level of HIF-1α or EGFR mRNA (respectively, relative risk (RR) = 2.8; p = 0.001 and RR = 1.9; p = 0.04; multivariate Cox´s regression analysis) is significantly associated with a poor prognosis in STS patients. The combination of both mRNAs in a multivariate Cox’s regression analysis resulted in an increased risk of early tumor-specific death of patients (RR = 3.1, p = 0.003) when both mRNA levels in the tumors were low. The EGFR protein level had no association with the survival of the patient’s cohort studied, and a higher level of HIF-1α protein associated only with a trend to significance (multivariate Cox’s regression analysis) to a poor prognosis in STS patients (RR = 1.9, p = 0.09). However, patients with low levels of HIF-1α protein and a high content of EGFR protein in the tumor had a three-fold better survival compared to patients without such constellation regarding the protein level of HIF-1α and EGFR. In a bivariate two-sided Spearman’s rank correlation, a significant correlation between the expression of HIF-1α mRNA and expression of EGFR mRNA (p < 0.001) or EGFR protein (p = 0.001) was found, additionally, EGFR mRNA correlated with EGFR protein level (p < 0.001). Our results show that low levels of HIF-1α mRNA or EGFR mRNA are negative independent prognostic markers for STS patients, especially after combination of both parameters. The protein levels showed a different effect on the prognosis. In addition, our analysis suggests a possible association between HIF-1α and EGFR expression in STS.eng
dc.description.sponsorshipOpen Access Publication Fund of the Martin Luther University Halle-Wittenberg-
dc.description.sponsorshipWilhelm-Roux-Program of BMBF/NBL3 Grant number FKZ: 16/18-
dc.publisherUniversitäts- und Landesbibliothek Sachsen-Anhalt-
dc.relation.isreferencedbydoi: 10.3390/ijms20020375-
dc.subjectHIF1 alphaeng
dc.subjectSoft tissue sarcomaeng
dc.subject.ddcDDC::600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten-
dc.titleLow HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differentlyeng
local.bibliographicCitation.journaltitleInt J Mol Sci. (International Journal of Molecular Sciences)-
local.bibliographicCitation.publishernameMDPI AG (Multidisciplinary Digital Publishing Institute AG)-
local.bibliographicCitation.publisherplaceBasel, Switzerland-
local.publisher.universityOrInstitutionMartin-Luther-Universität Halle-Wittenberg-
Appears in Collections:Medizinische Fakultät MLU

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