PO.CL01.17 · 临床研究
Clinical and molecular features of CD276 (B7H3) in liver metastases of pancreatic cancer
作者与单位
摘要 Abstract
Introduction: CD276 (B7-H3), a modulator of tumor-microenvironment as affecting cadherin expression, has a prognostic impact in the different types of cancers including pancreatic ductal adenocarcinoma (PDAC). In metastatic PDAC, these roles in CD276 have not been fully understood. Using liver metastasis (LM)-derived transcriptome and reversed-phased protein array (RPPA) data, we evaluated CD276 expressions of LMs on clinical outcomes and molecular features in metastatic PDAC.
Methods: Needle-biopsied specimens from treatment-naïve LMs of PDAC were collected for protein and RNA extraction. A 435-protein expression was measured on RPPA. The impact of each protein level stratified with median value was tested using univariate Cox regression hazard model. The top 3 prognostic proteins and clinical prognostic factors such as Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and serum level of C-reactive protein (CRP) were evaluated in multivariate Cox regression hazard model. To investigate clinical relevance of CD276, our study population was stratified based on the median value of CD276 mRNA expression level detected on cDNA microarray, followed by differential gene expression analysis and subsequent Gene Ontology (GO) analysis between the two groups surveying for CD276 high-related genes/ pathways.
Results: RPPA data was obtained from LMs of 42 patients (Male: 64.2%; median age: 66 years). The tumor proteome data showed that overall survival times were prolonged in the patients with intratumoral high expression of Aurora-A, PGDFR-beta, and CD276 as compared to those without. Independent prognostic impacts were found in CD276 high (hazard ratio: 0.148 [95% confidence interval: 0.005 to 0.434]), ECOG-PS 1 or more (4.651 [1.713 to 12.63]), and CRP high (6.440 [2.498 to 16.60]) in multivariate analysis. Transcriptome data were evaluated in 40 of 42 LMs. The 116 genes were identified as CD276 high-related genes. GO terms associated with CD276 high were cadherin binding (GO:0045296), cell adhesion molecule binding (GO:0050839), and protein binding (GO:0005515). LMs with high CD276 protein expression showed high protein expression in E-cadherin (P<0.001) and tended to be low in protein expression of N-cadherin (P=0.097) as compared to those with low CD276 protein expression.
Conclusion: High expression of CD276 protein in liver metastasis of PDAC was an independent favorable prognostic factor and related to increasing E-cadherin expression in tumor. Further study is needed to explore the roles of CD276 in metastatic PDAC.
利益披露 Disclosure
G. Igarashi, None.
S. Mitsunaga,
Toray Industries, Inc ).
Ajinomoto Co., Inc ).
Mitsui Chemicals, Inc ).
Taiho Innovations, LLC ).
Taiho Pharmaceutical Co., Ltd ).
Tensegrity Pharma, Inc ).
Pfizer Japan Inc ).
Ono Pharmaceutical Co.,Ltd ).
Astellas Pharma Inc ).
Chugai Pharmaceutical Co., Ltd ).
N. Okumura, None..
K. Inoue, None..
T. Taira, None..
T. Shibuki, None.
T. Satake,
Ono ).
Servier ).
M. Amisaki,
GxD Inc ).
M. Sasaki,
AstraZeneca ).
Boehringer Ingelheim ).
MSD ).
Nihon Servier ).
Taiho ).
H. Takahashi, None.
H. Imaoka,
Ono Pharmaceutical ).
Servier ).
Novartis ).
Boehringer Ingelheim ).
M. Ikeda,
AstraZeneca ).
Abbvie ).
Amgen ).
Bristol Myers Squibb ).
Chugai ).
Chiome Bioscience ).
Delta-Fly Pharma ).
Eisai ).
Eli Lilly Japan ).
Invitae ).
MSD ).
J-Pharma ).
Merck biopharma ).
Merus N.V. ).
Novartis ).
Nihon Servier ).
Ono ).
Syneos Health ).
Rakuten Medical ).
Taiho ).