Dataset Information

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

ABSTRACT: BACKGROUND: It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants. METHODS: We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b and -c). RESULTS: The multivariate Cox's proportional hazard regression model revealed that high mRNA expression levels of OPN splice variants are significantly associated with poor prognosis in STS patients (n = 124). Women (n = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8; OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P < 0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3). CONCLUSION: Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for STS patients. Further studies are needed to clarify the impact of the OPN splice variants on prognosis.

SUBMITTER: Hahnel A

PROVIDER: S-EPMC3364873 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Hahnel Antje A Wichmann Henri H Greither Thomas T Kappler Matthias M Würl Peter P Kotzsch Matthias M Taubert Helge H Vordermark Dirk D Bache Matthias M

BMC cancer 20120402

<h4>Background</h4>It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants.<h4>Methods</h4>We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used t ...[more]

PMID: 22471890

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Project description:BACKGROUND:The human leucine-rich, repeat-containing G protein-coupled receptor 5 (LGR5) is a stem cell marker in numerous adult tissues and is overexpressed in a large number of human carcinoma including colon cancer, breast cancer and oral squamous cell carcinomas (OSCC). The role of the full length transcript (LGR5FL) in progression and prognosis of several cancers was reported. However, the biological function of three splice variants of LGR5 (LGR5?5, LGR5?8 and LGR5?5-8) has yet to be thoroughly investigated. METHODS:Seventy-eight frozen tumor samples from adult OSCC patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of full length LGR5, the splice variant of LGR5 lacking exon 5 (LGR5?5), the splice variant of LGR5 lacking exon 8 (LGR5?8) and the mRNA level of all known transcript variants together (LGR5all) were quantified and correlated to overall and disease-specific survival of OSCC patients, clinical parameters and the mRNA level of different tumor-associated markers. RESULTS:An elevated level of tumoral LGR5?5 mRNA, but not LGR5FL, LGR5?8 or LGR5all mRNA was significantly associated with a poor prognosis for the overall and disease-specific survival of OSCC patients (hazard ratio (HR)?=?2.0; p?=?0.02; 95% CI: 1.1-3.7; HR?=?3.2; p?=?0.01; 95% CI: 1.3-8.0; multivariable Cox regression), respectively. Additionally, a higher tumoral level of LGR5?5 mRNA in primary tumors was associated with the occurrence of regional lymph node metastases in OSCC patients (odds ratio (OR)?=?3.1; p?=?0.022; 95% CI: 1.2-7.9; binary logistic regression). Furthermore, the mRNA levels of all investigated LGR5 transcript variants were significantly correlated with the mRNA expression of Wnt-target genes and markers of epithelial-to-mesenchymal transition (EMT). CONCLUSION:The mRNA level of the LGR5 splice variant LGR5?5 is an independent negative prognostic marker for overall and disease-specific survival and metastasis in OSCC patients. Additionally, we suggest, all LGR5 transcript variants are involved in the EMT process mainly through activating the Wnt-signalling pathway.

Dataset Information

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

Publications

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

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