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Osteopontin is a marker for cancer aggressiveness and patient survival.

Weber GF, Lett GS, Haubein NC - Br. J. Cancer (2010)

Bottom Line: Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer.Osteopontin levels are also markers for stage, grade, and early tumor progression in multiple cancers, reflecting a common molecular underpinning for distinct clinical measures.Osteopontin has value as a clinical tumor progression marker.

View Article: PubMed Central - PubMed

Affiliation: University of Cincinnati Academic Health Center, James L. Winkle College of Pharmacy, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA. georg.weber@uc.edu

ABSTRACT

Background: Only a fraction of molecular cancer markers identified in the scientific literature have found clinical use. Specifically, few predictors of invasiveness are established in diagnostics. Meta-analysis is a valuable tool for biomarker validation. Here, we evaluate Osteopontin as a marker for tumor aggressiveness (grade, stage, early progression) and patient survival.

Methods: Publications through 2008 with the keywords 'osteopontin AND cancer' were retrieved. Titles and abstracts were screened for studies presenting original data on human subjects. This left 228 publications for data extraction. We applied categorical data analysis for testing the relationship between Osteopontin and a clinical variable.

Results: Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer. Further, Osteopontin levels correlated with tumor grade and stage for all tumors combined and for several individual tumor types. Osteopontin levels were significantly associated with the early progression of eight cancers, independent in one, and inversely correlated in two.

Conclusions: Osteopontin is significantly associated with survival in several forms of cancer. Osteopontin levels are also markers for stage, grade, and early tumor progression in multiple cancers, reflecting a common molecular underpinning for distinct clinical measures. Osteopontin has value as a clinical tumor progression marker.

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Osteopontin in overall survival and in disease-free/relapse-free survival. (A) Overall survival and Osteopontin ranks for all cancers combined. (B) Disease-free survival and Osteopontin ranks for all cancers combined. (C) Probability Distribution Function for independent Osteopontin and overall survival ranks. The measured value for Osteopontin data is shown as a vertical line. (D) Probability Density Function for independent Osteopontin and disease free survival ranks. Measured value for Osteopontin data is shown as a vertical line.
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fig1: Osteopontin in overall survival and in disease-free/relapse-free survival. (A) Overall survival and Osteopontin ranks for all cancers combined. (B) Disease-free survival and Osteopontin ranks for all cancers combined. (C) Probability Distribution Function for independent Osteopontin and overall survival ranks. The measured value for Osteopontin data is shown as a vertical line. (D) Probability Density Function for independent Osteopontin and disease free survival ranks. Measured value for Osteopontin data is shown as a vertical line.

Mentions: We applied categorical meta-analysis to the evaluation of Osteopontin as a prognostic marker. The distribution of ranks for published overall and disease-free/relapse-free survival versus measured Osteopontin levels displayed an aggregation along the diagonal in bar graphs, indicating a good correspondence for higher Osteopontin rank to lower mean survival time (Figure 1A and B). To further quantify these results, we determined the probability that for two patient groups selected at random from a study, the one that had the higher Osteopontin score would also have a shorter mean survival time. This resulted in a probability of 90.8%, P<1 × 10−5 for overall survival and a probability of 92.9%, P=1 × 10−4 for disease-free/relapse-free survival, where the significance was estimated using a permutation test. These results indicate that Osteopontin rank is a good predictor of survival outcome rank within a study. The actual probability calculated from the meta-analysis of the data was significant when compared to the estimated probability distribution under the hypothesis that Osteopontin and mean survival time are independent (Figure 1C and D). When broken down to individual cancers, the association between Osteopontin levels and overall survival was significant for lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer (Table 2). Similar results were obtained using the meta-analysis function in Oncomine (Supplement 1). For several cancer types, only one published study was available. Those cases were excluded from the meta-analysis.


Osteopontin is a marker for cancer aggressiveness and patient survival.

Weber GF, Lett GS, Haubein NC - Br. J. Cancer (2010)

Osteopontin in overall survival and in disease-free/relapse-free survival. (A) Overall survival and Osteopontin ranks for all cancers combined. (B) Disease-free survival and Osteopontin ranks for all cancers combined. (C) Probability Distribution Function for independent Osteopontin and overall survival ranks. The measured value for Osteopontin data is shown as a vertical line. (D) Probability Density Function for independent Osteopontin and disease free survival ranks. Measured value for Osteopontin data is shown as a vertical line.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966627&req=5

fig1: Osteopontin in overall survival and in disease-free/relapse-free survival. (A) Overall survival and Osteopontin ranks for all cancers combined. (B) Disease-free survival and Osteopontin ranks for all cancers combined. (C) Probability Distribution Function for independent Osteopontin and overall survival ranks. The measured value for Osteopontin data is shown as a vertical line. (D) Probability Density Function for independent Osteopontin and disease free survival ranks. Measured value for Osteopontin data is shown as a vertical line.
Mentions: We applied categorical meta-analysis to the evaluation of Osteopontin as a prognostic marker. The distribution of ranks for published overall and disease-free/relapse-free survival versus measured Osteopontin levels displayed an aggregation along the diagonal in bar graphs, indicating a good correspondence for higher Osteopontin rank to lower mean survival time (Figure 1A and B). To further quantify these results, we determined the probability that for two patient groups selected at random from a study, the one that had the higher Osteopontin score would also have a shorter mean survival time. This resulted in a probability of 90.8%, P<1 × 10−5 for overall survival and a probability of 92.9%, P=1 × 10−4 for disease-free/relapse-free survival, where the significance was estimated using a permutation test. These results indicate that Osteopontin rank is a good predictor of survival outcome rank within a study. The actual probability calculated from the meta-analysis of the data was significant when compared to the estimated probability distribution under the hypothesis that Osteopontin and mean survival time are independent (Figure 1C and D). When broken down to individual cancers, the association between Osteopontin levels and overall survival was significant for lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer (Table 2). Similar results were obtained using the meta-analysis function in Oncomine (Supplement 1). For several cancer types, only one published study was available. Those cases were excluded from the meta-analysis.

Bottom Line: Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer.Osteopontin levels are also markers for stage, grade, and early tumor progression in multiple cancers, reflecting a common molecular underpinning for distinct clinical measures.Osteopontin has value as a clinical tumor progression marker.

View Article: PubMed Central - PubMed

Affiliation: University of Cincinnati Academic Health Center, James L. Winkle College of Pharmacy, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA. georg.weber@uc.edu

ABSTRACT

Background: Only a fraction of molecular cancer markers identified in the scientific literature have found clinical use. Specifically, few predictors of invasiveness are established in diagnostics. Meta-analysis is a valuable tool for biomarker validation. Here, we evaluate Osteopontin as a marker for tumor aggressiveness (grade, stage, early progression) and patient survival.

Methods: Publications through 2008 with the keywords 'osteopontin AND cancer' were retrieved. Titles and abstracts were screened for studies presenting original data on human subjects. This left 228 publications for data extraction. We applied categorical data analysis for testing the relationship between Osteopontin and a clinical variable.

Results: Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer. Further, Osteopontin levels correlated with tumor grade and stage for all tumors combined and for several individual tumor types. Osteopontin levels were significantly associated with the early progression of eight cancers, independent in one, and inversely correlated in two.

Conclusions: Osteopontin is significantly associated with survival in several forms of cancer. Osteopontin levels are also markers for stage, grade, and early tumor progression in multiple cancers, reflecting a common molecular underpinning for distinct clinical measures. Osteopontin has value as a clinical tumor progression marker.

Show MeSH
Related in: MedlinePlus