Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma.

Abstract

BACKGROUND:

Osteopontin (OPN) is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC) in humans has not yet been investigated.

METHODS:

We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients' biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin.

RESULTS:

Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF). An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin.

CONCLUSIONS:

A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

• Authors: Sheng-Dean Luo, Yi-Ju Chen, Chien-Ting Liu, Kun-Ming Rau, Yi-Ching Chen, Hsin-Ting Tsai, Chang-Han Chen, Tai-Jan Chiu
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 508587 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 26491674 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Taxoids
• Osteopontin
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Carcinoma, Squamous Cell (drug therapy, metabolism, mortality, pathology)
• Cisplatin (administration & dosage)
• Disease-Free Survival
• Drug Resistance, Neoplasm (drug effects)
• Female
• Fluorouracil (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Middle Aged
• Mouth Neoplasms (drug therapy, metabolism, mortality, pathology)
• Neoplasm Proteins (biosynthesis)
• Osteopontin (antagonists & inhibitors)
• Survival Rate
• Taxoids (administration & dosage)