scholarly journals Low HIF-1α and low EGFR mRNA Expression Significantly Associate with Poor Survival in Soft Tissue Sarcoma Patients; the Proteins React Differently

2018 ◽  
Vol 19 (12) ◽  
pp. 3842 ◽  
Author(s):  
Swetlana Rot ◽  
Helge Taubert ◽  
Matthias Bache ◽  
Thomas Greither ◽  
Peter Würl ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Protein Level ◽  
Poor Prognosis ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Increased Risk ◽  
Cox's Regression ◽  
Low Levels

In 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.

scholarly journals Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma

2019 ◽  
Vol 20 (2) ◽  
pp. 375 ◽  
Author(s):  
Alexander W. Eckert ◽  
Susanne Horter ◽  
Daniel Bethmann ◽  
Johanna Kotrba ◽  
Tom Kaune ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Carbonic Anhydrase ◽  
Protein Level ◽  
Normal Tissue ◽  
Mrna Level ◽  
Mrna Levels ◽  
Cox's Regression ◽  
Carbonic Anhydrase 9

s: Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.

scholarly journals Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients

BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Antje Hahnel ◽  
Henri Wichmann ◽  
Thomas Greither ◽  
Matthias Kappler ◽  
Peter Würl ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Splice Variants ◽  
Prognostic Impact ◽  
Mrna Levels

scholarly journals Integrative Clustering Reveals a Novel Subtype of Soft Tissue Sarcoma With Poor Prognosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhenhua Zhu ◽  
Zheng Jin ◽  
Haibo Zhang ◽  
Mei Zhang ◽  
Dahui Sun
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Poor Prognosis

scholarly journals Impact of sarcopenia in advanced and metastatic soft tissue sarcoma

2021 ◽  
Author(s):  
Dennis Strassmann ◽  
Bennet Hensen ◽  
Viktor Grünwald ◽  
Katharina Stange ◽  
Hendrik Eggers ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cox Regression ◽  
Therapy Response ◽  
Prognostic Impact ◽  
Patient Counseling ◽  
Skeletal Muscle Index ◽  
Prognostic Parameter ◽  
Dismal Prognosis ◽  
Metastatic Soft Tissue Sarcoma

Abstract Introduction Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. Methods 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. Results 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9–6.0] vs. 16 months [95%CI 8.8–23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4–4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). Conclusion This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

scholarly journals Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma

2004 ◽  
Vol 10 (13) ◽  
pp. 4464-4471 ◽  
Author(s):  
Kårstein Måseide ◽  
Rita A. Kandel ◽  
Robert S. Bell ◽  
Charles N. Catton ◽  
Brian O’Sullivan ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Carbonic Anhydrase ◽  
Poor Prognosis ◽  
Carbonic Anhydrase Ix

scholarly journals The Prognostic Impact of Unplanned Excisions in a Cohort of 728 Soft Tissue Sarcoma Patients: A Multicentre Study

2017 ◽  
Vol 24 (6) ◽  
pp. 1596-1605 ◽  
Author(s):  
Maria Anna Smolle ◽  
Per-Ulf Tunn ◽  
Elisabeth Goldenitsch ◽  
Florian Posch ◽  
Joanna Szkandera ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Multicentre Study ◽  
Prognostic Impact

scholarly journals PV-0048: Prognostic impact of tumor size and response in neoadjuvant radiotherapy of soft tissue sarcoma

2017 ◽  
Vol 123 ◽  
pp. S21
Author(s):  
A. Cortesi ◽  
A. Arcelli ◽  
R. Frakulli ◽  
L. Giaccherini ◽  
S. Bisello ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Prognostic Impact ◽  
Neoadjuvant Radiotherapy

scholarly journals Prevalence and prognostic impact of comorbidity in soft tissue sarcoma: A population-based cohort study

2014 ◽  
Vol 53 (9) ◽  
pp. 1188-1196 ◽  
Author(s):  
Katja Maretty-Nielsen ◽  
Ninna Aggerholm-Pedersen ◽  
Akmal Safwat ◽  
Steen Baerentzen ◽  
Alma B. Pedersen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Population Based ◽  
Prognostic Impact

Impact of interdisciplinary sarcoma board evaluation on treatment outcome of primary soft-tissue sarcoma patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23540-e23540
Author(s):  
Jana Kaethe Striefler ◽  
Annika Strönisch ◽  
Daniel Rau ◽  
David Kaul ◽  
Georgios Koulaxouzidis ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Stage ◽  
Quality Parameters ◽  
Low Grade ◽  
Early Presentation ◽  
Risk Of Death ◽  
Increased Risk ◽  
Interdisciplinary Approaches

e23540 Background: Early presentation of soft-tissue sarcoma (STS) patients to a specialized sarcoma center including discussion in the interdisciplinary sarcoma board (ISB) prior to surgery is essential to the treatment of sarcomas. This approach significantly improves patient survival and guideline coherence. However, there exists only limited information on the adherence to the recommendations of the ISB. Accordingly, we decided to analyze a STS cohort at a large German sarcoma center focusing on outcome parameters and adherence to quality parameters defined by the German Cancer Society (Deutsche Krebsgesellschaft). Methods: In a retrospective data analysis, we identified n = 230 adult patients presented at the ISB of the Charité–Universitätsmedizin Berlin in Germany from January 2015 until December 2019. Inclusion criteria were as follows: newly diagnosed STS, presentation during first-line therapy and recommendation of at least one treatment modality such as surgery, chemotherapy, radiotherapy, regional hyperthermia or follow-up by the ISB. Clinical and follow up data was collected by using the hospital information system and the outpatient network. Results: Our patient cohort included 53% male and 47% female patients with a median age of 58 years (range 19-96). The majority (86%) showed a localized tumor stage, while 14% already had metastases. In 24% of the cases the sarcomas were classified as low-grade, in 76% as high-grade. Surgery was recommended for 66% of the cases, for 80% of them combined with chemotherapy, radiotherapy or hyperthermia. 14% of the patients received a recommendation for all 4 modalities. For 9% of the patients, chemotherapy alone was recommended. Both overall survival and progression-free survival was significantly higher in the group with complete adherence to the recommendations of the ISB (p < 0.001). The worst prognosis was found in patients unable to adhere to the recommendations due to rapid progression or complications of the therapy (HR for death 15.06, 95%CI 7.94-32.22). If one recommended modality was not carried out, there also was a higher risk of death (HR 4.38, 95%CI 1.75-10.96). Most common reasons were patient refusal or individual decision by the treating physician. A metastasized tumor stage was associated with an increased risk of death (HR 2.62, 95%CI 1.45-4.75). In contrast, neither the histological grading (low vs. high) nor age did influence the mortality significantly. Conclusions: In our cohort of STS patients, survival depends significantly on adherence to the recommendations of the ISB. Our analysis at a German sarcoma center is in line with previous international reports demonstrating the importance of interdisciplinary decisions and therapeutic adherence. We hereby underline the essential role of interdisciplinary approaches in care of STS patients and the effort to implement defined quality parameters.

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