title: Loss of stromal caveolin-1 expression: a novel tumor microenvironment biomarker that can predict poor clinical outcomes for pancreatic cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shan
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D051242:Caveolin 1 / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D051242:Caveolin 1