Osteopontin is a marker for cancer aggressiveness and patient survival

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.

Figure 1

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.

Figure 2

By categorical meta-analysis, Osteopontin levels correlate with stage and grade of cancers. (A) The Pearson χ² test of ranked Osteopontin immunohistochemistry scores with tumor grade and stage shows a significant dependence between Osteopontin rank and clinical variable. (B) The bar graphs of Osteopontin rank versus rank of grade or stage display an aggregation of data along the diagonal, indicating a positive relationship between Osteopontin levels and clinical variables. The associations are statistically significant for grade and node positivity, but not for stage T and M. (C) Expanded analysis of grade and stage ranks to all published measures. In five studies with duplicate data sets only the immunohistochemistry results were used. We computed a measure analogous to that represented by the area under a ROC curve (see Methods). For all grade and stage measures, Osteopontin is a significant positive indicator.