Antigenic changes in cancer cells can be recognized by the immune system of patients themselves and presented as immune responses to factors involved in malignant transformation. This is manifested in several ways, one of which is the appearance of circulating autoantibodies. These autoantibodies, which have been called """"""""reporters"""""""" from the immune system, identify the antigenic changes in cellular factors involved in the transformation process. Circulating autoantibodies from cancer patients have been used to isolate the cognate tissue antigens, many of which have been shown to be cellular factors participating in known tumorigenesis pathways. These cancer-related tissue antigens have been generally called tumor-associated antigens (TAAs). In the case of liver cancer, especially hepatocellular carcinoma (HCC), antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop novel autoantibodies that were not present during the preceding chronic liver disease phase. The hypothesis is that transition to malignancy can be associated with autoantibody responses to certain cellular proteins that might have some role in tumorigenesis. It is proposed that the information that the cancer patient's immune system is conveying in the form of autoantibodies to TAAs should be utilized to a greater extent in identifying early signs of tumorigenesis. There are three specific aims in this grant application: (1) Establish more precise time lines to determine when autoantibodies to TAAs appear as early predictors of HCC in patients with antecedent chronic viral hepatitis and liver cirrhosis;(2) Identify and characterize novel TAAs in HCC using a proteome-based technology, and further validate the potential value of the identified TAAs as cancer biomarkers;(3) Establish rigorous criteria for designation of an autoantibody to a TAA as a cancer biomarker, examine candidate TAAs for sensitivity and specificity of anti-TAA antibody response, and further develop customized TAA arrays that can be used to enhance anti-TAA antibody detection in HCC.

Public Health Relevance

In this proposed study, we will identify and validate the tumor-associated antigen (TAA) and anti-TAA antibody systems as diagnostic biomarkers in liver cancer, and further develop TAA arrays for cancer immunoscreening, which may lead to early preventive or therapeutic interventions aimed at suppressing or slowing the appearance of a tumor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Enhancement Award (SC1)
Project #
5SC1CA166016-03
Application #
8509638
Study Section
Special Emphasis Panel (ZGM1-MBRS-2 (GC))
Program Officer
Wali, Anil
Project Start
2011-08-05
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$245,928
Indirect Cost
$81,428
Name
University of Texas El Paso
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
132051285
City
El Paso
State
TX
Country
United States
Zip Code
79968
Liu, Mei; Varela-Ramirez, Armando; Li, Jitian et al. (2015) Humoral autoimmune response to nucleophosmin in the immunodiagnosis of hepatocellular carcinoma. Oncol Rep 33:2245-52
Liu, Weihong; De La Torre, Ignacio García; Gutiérrez-Rivera, María Cristina et al. (2015) Detection of autoantibodies to multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer. Tumour Biol 36:1307-12
Liu, W; Li, Y; Wang, B et al. (2015) Autoimmune Response to IGF2 mRNA-Binding Protein 2 (IMP2/p62) in Breast Cancer. Scand J Immunol 81:502-7
Peng, Bo; Lei, Ningjing; Chai, Yurong et al. (2015) CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer. Mol Biosyst 11:105-14
Zhu, Qing; Han, Su-Xia; Zhou, Cong-Ya et al. (2015) Autoimmune response to PARP and BRCA1/BRCA2 in cancer. Oncotarget 6:11575-84
Sun, Wenqing; Tseng, Tzu-Liang Bill; Qian, Wei et al. (2015) Using multiscale texture and density features for near-term breast cancer risk analysis. Med Phys 42:2853-62
Peng, Bo; Chai, Yurong; Li, Yang et al. (2015) CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer. BMC Cancer 15:895
Dai, Liping; Ren, Pengfei; Liu, Mei et al. (2014) Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma. Clin Immunol 152:127-39
Liu, Xinxin; Peng, Bo; Li, Yang et al. (2014) p90/CIP2A mediates breast cancer cell proliferation and apoptosis. Mol Biol Rep 41:7471-8
Han, Su-xia; Wang, Jing; Wang, Li-juan et al. (2014) The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis. Tumour Biol 35:6149-57

Showing the most recent 10 out of 22 publications