BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the on...

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Vydané v:	PloS one Ročník 7; číslo 6; s. e38541
Hlavní autori:	Le Page, Cécile, Marineau, Alexandre, Bonza, Patrick K., Rahimi, Kurosh, Cyr, Louis, Labouba, Ingrid, Madore, Jason, Delvoye, Nathalie, Mes-Masson, Anne-Marie, Provencher, Diane M., Cailhier, Jean-François
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 07.06.2012 Public Library of Science (PLoS)
Predmet:	Adult Aged Aged, 80 and over Antibodies Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - metabolism Automobile industry B cells Biology Biomarkers Blotting, Western Butyrophilin Butyrophilins Cancer CD20 antigen CD3 antigen CD4 antigen CD8 antigen Cell growth Cell Line, Tumor Chemokines Chemotherapy Cohort Studies Cytokines Development and progression Epithelial cells Female Gene expression Health risks Humans Immune system Immunohistochemistry Immunohistochemistry - statistics & numerical data Immunoregulation Infiltration Inflammation Kaplan-Meier Estimate Lectins, C-Type - metabolism Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - metabolism Lymphocytes, Tumor-Infiltrating - pathology Mannose-Binding Lectins - metabolism Medical prognosis Medicine Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Membrane Proteins - genetics Membrane Proteins - metabolism Metastases Middle Aged Multivariate Analysis Mutation Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - metabolism Neoplasms, Glandular and Epithelial - pathology Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Patients Prognosis Proportional Hazards Models Protein Isoforms - metabolism Proteins Quality Receptors, Cell Surface - metabolism Risk assessment RNA T cells T-Lymphocytes - metabolism T-Lymphocytes - pathology Tissue Array Analysis - statistics & numerical data Transcription factors Transfection Trends Tumors Canada Montreal Quebec Canada Quebec Canada
ISSN:	1932-6203, 1932-6203
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Shrnutí:	BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR=0.651, p=0.006 and HR=0.642, p=0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR=1.355 p=0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: CLP PB AMMM DP LC IL AM JFC. Performed the experiments: CLP AM PB ND LC. Analyzed the data: CLP AM KR. Contributed reagents/materials/analysis tools: JM JFC DP AMMM. Wrote the paper: CLP LC DP JFC AMMM.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0038541