Identification of tumor‐associated plasma biomarkers using proteomic techniques: From mouse to human

Abstract

In an effort to identify tumor-associated proteins from plasma of tumor-bearing mice that may be used as diagnostic biomarkers, we developed a strategy that combines a tumor xenotransplantation model in nude mice with comparative proteomic technology. Five human cancer cell lines (SC-M1, HONE-1, CC-M1, OECM1, GBM 8401) derived from stomach, nasopharyngeal, colon, oral and brain cancers were subcutaneously inoculated into nude mice and compared to control nude mice injected with phosphate-buffered saline. One month later, plasma from mice inoculated with cancer cells was collected for proteomic analysis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Comparison of plasma 2-DE maps from tumor-bearing mice with those produced from control mice revealed the overexpression of several mouse acute phase proteins (APPs) such as haptoglobin. Another APP, serum amyloid A (SAA), was found only in mice bearing tumors induced by the stomach cancer cell line SC-M1, which has not previously been demonstrated in xenotransplatation experiment. Furthermore, by using immunohistochemistry, SAA and haptoglobin were found to originate from the mouse hosts and not from the human cancer cell line donors. The protein alterations were further confirmed on patients with stomach cancers where up-regulated levels of SAA were also observed. These results indicate that APPs may be used as nonspecific tumor-associated serum markers. SAA in particular may serve as a potential marker for detecting stomach cancer. Taken together, the combination of the xenotransplatation model in nude mice and proteomics analysis provided a valuable impact for clinical applications in cancer diagnostics. In addition, our findings demonstrate that a panel of APPs might serve as screening biomarkers for early cancer detection.

Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry

“…Among the APPs found in SARS patients, SAA and haptoglobin have been widely used as inflammatory markers for evaluating the status of infection and inflammatory lesions in veterinary medicine (19). Although SAA is not as commonly used in human medicine as C-reactive protein (CRP), it is more sensitive to acute response than CRP (17,20,21).…”

Identification of αB-Crystallin, a Biomarker of Renal Cell Carcinoma by SELDI-TOF MS

“…In most cases, the markers identified were associated with several types of cancer or other diseases, e.g., SAA as a biomarker of nasopharyngeal cancer (10), ovarian cancer (9) and prostate cancer (4,14) or apolipoprotein A-I being linked to ovarian cancer (14), colorectal cancer (15), diabetes and cardiovascular disease (16). These proteins are thus not specific biomarkers for one type of malignancy but reflect generalized pathological processes that occur in a subset of patients with cancer or other types of disease (17).…”

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

“…NSE is overexpressed in small cell lung cancer which origins from neuroendocrineneoplasm. So NSE can be used as specific tumor marker (Juan et al, 2004) in small cell lung cancer and is important in the diagnosis of small cell lung cancer. In this study, the specificity of NSE in detection of lung cancer was higher (97.9%), but the sensitivity was lower (26.9 %).…”