B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells
et al. (2013) B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and
Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells. PLoS ONE 8(10): e76012. doi:10.1371/journal.pone.0076012
B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells
Sheng-Jia Shi 0 1
Li-Juan Wang 0 1
Guo-Dong Wang 0 1
Zhang-Yan Guo 0 1
Ming Wei 0 1
Yan-Ling Meng 0 1
An- 0 1
Gang Yang 0 1
Wei-Hong Wen 0 1
0 Editor: John Souglakos, University General Hospital of Heraklion and Laboratory of Tumor Cell Biology, School of Medicine, University of Crete , Greece
1 1 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University , Xi'an, China , 2 Department of Oncology, the First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University , Xi'an, China , 3 Department of Urology, Xijing Hospital, Fourth Military Medical University , Xi'an, China , 4 Department of Comprehensive Medicine, 323 Hospital of the Chinese People's Liberation Army , Xi'an , China
Background And Objective: The investigation concerning the B7-H1 expression in colorectal cancer cells is at an early stage. It is unclear whether B7-H1 expression may have diagnostic or prognostic value in colorectal carcinoma. Additionally, how B7-H1 is associated with the clinical features of colorectal carcinoma is not known. In order to investigate the relationship between B7-H1 and colorectal cancer, we analyzed B7-H1 expression and its effect in clinical specimens and HCT116 cells. Methods: Paraffin-embedded specimens from 143 eligible patients were used to investigate the expression of CD274 by immunohistochemistry. We also examined whether B7-H1 itself may be related to cell proliferation, apoptosis, migration and invasion in colon cancer HCT116 cells. Results: Our results show that B7-H1 was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status and TNM (Tumor Node Metastasis) stage. Patients with positive B7-H1 expression showed a trend of shorter survival time. Using multivariate analysis, we demonstrate that positive B7-H1 expression is an independent predictor of colorectal carcinoma prognosis. Our results indicate that B7-H1 silencing with siRNA inhibits cell proliferation, migration and invasion. Furthermore, cell apoptosis was also increased by B7-H1 inhibition. Conclusions: Positive B7-H1 expression is an independent predictor for colorectal carcinoma prognosis. Moreover, knockdown of B7-H1 can inhibit cell proliferation, migration and invasion.
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Funding: This work was supported by the National Natural Science Foundation of China (No.30873004, 30973000 and 81171924) and Natural Science
Foundation of Shan xi Province (No.2011JM4006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation
of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
These authors contributed equally to this work.
Colorectal carcinoma is the third most frequently diagnosed
malignancy in the world and the fifth leading cause of death
among cancer patients in China [1]. Due to a lack of effective
diagnostic markers, most colorectal cancer patients have
distant metastases (stage IV) at diagnosis. The most effective
colorectal cancer treatment is surgery. However, the lack of
accurate prognosis markers makes it difficult to predict patient
survival time after surgery. Thus, new and effective markers for
diagnosis and prognosis are required in the clinic.
The co-stimulatory molecule B7 homolog 1 (B7-H1 or
CD274) is a recently identified ligand for the co-inhibitory
receptor programmed death-1 (PD-1 or CD279) [2,3]. B7-H1 is
expressed on T cells, B cells, macrophages and dendritic cells.
The expression of B7-H1 can be further upregulated upon
lymphocytes, B7-H1 has also been detected at low levels on
pancreatic islets and syncytiotropho-blasts in the placenta [5,6].
Traditionally, the function of B7-H1 on antigen-presenting cells
is achieved through binding with PD-1 on T cell, which is
thought to have an important role in the induction and
maintenance of immune tolerance [7-9].
In addition to the expression on lymphocytes and normal
tissue, aberrant B7-H1 expression has also been found in
various human malignancies. Tumor types including squamous
cell carcinomas of the lung, esophagus, head and neck, and
other types of carcinomas such as ovarian, bladder, breast
cancer, melanoma and glioma also express B7-H1 [10-16]. The
expression of tumor-associated B7-H1 is correlated with poor
prognosis and high malignancy grade. The blockade of
tumorassociated B7-H1 has been shown to promote tumor
regression in vivo in several murine tumor transplants
[10,12,17,18]. PD-1 expression is upregulated on
tumorinfiltrating lymphocytes, and it has been proposed that B7-H1
expresse (...truncated)