Loss of stromal caveolin-1 expression: a novel tumor microenvironment biomarker that can predict poor clinical outcomes for pancreatic cancer.

Abstract

AIMS:

Cancer development and progression is not only associated with the tumor cell proliferation but also depends on the interaction between tumor cells and the stromal microenvironment. A new understanding of the role of the tumor microenvironment suggests that the loss of stromal caveolin-1 (Cav-1) as a key regulator may become a potential therapy target. This study aims to elucidate whether stromal Cav-1 expression in pancreatic cancer can be a strong prognosis biomarker.

METHODS:

Tissue samples from 45 pancreatic cancer patients were studied. Parenchyma and stroma were separated and purified using laser capture microdissection. Stromal Cav-1 expression was measured from pancreatic cancer, paraneoplastic, and normal tissue using immunohistochemistry. We analyzed the correlation of stromal Cav-1 expression with clinicopathologic features and prognostic indicators, such as tumor marker HER-2/neu gene.

RESULTS:

Specimens from six patients (13.3%) showed high levels of stromal Cav-1 staining, those from eight patients (17.8%) showed a lower, intermediate level of staining, whereas those from 31 patients (68.9%) showed an absence of staining. Cav-1 expression in cancer-associated fibroblasts was lower than that in paracancer-associated and in normal fibroblasts. Stromal Cav-1 loss was associated with TNM stage (P = 0.018), lymph node metastasis (P = 0.014), distant metastasis (P = 0.027), and HER-2/neu amplification (P = 0.007). The relationships of age, sex, histological grade, and tumor size with stromal Cav-1 expression were not significant (P>0.05). A negative correlation was found between circulating tumor cells and stromal Cav-1 expression (P<0.05).

CONCLUSION:

The loss of stromal Cav-1 in pancreatic cancer was an independent prognostic indicator, thus suggesting that stromal Cav-1 may be an effective therapeutic target for patients with pancreatic cancer.

• Authors: Tao Shan, Hongwei Lu, Hong Ji, Yiming Li, Jian Guo, Xi Chen, Tao Wu
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e97239 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24949874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Caveolin 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (biosynthesis)
• Caveolin 1 (biosynthesis)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Pancreatic Neoplasms (genetics, pathology)
• Prognosis
• Tumor Microenvironment (genetics)