Enhanced Detection of Early Hepatocellular Carcinoma by Serum SELDI-TOF Proteomic Signature Combined with Alpha-Fetoprotein Marker

Abstract

BackgroundBiomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha-fetoprotein (AFP) level in HCC diagnosis.Patients and MethodsSerum samples were obtained from 120 HCC and 120 LC patients for biomarker discovery and validation studies. ProteinChip technology was employed for generating SELDI-TOF proteomic features and analyzing serum proteins/peptides.ResultsA diagnostic model was established by CART algorithm, which is based on 5 proteomic peaks with m/z values at 3324, 3994, 4665, 4795, and 5152. In the training set, the CART algorithm could differentiate HCC from LC subjects with a sensitivity and specificity of 98% and 95%, respectively. The results were assessed in blind validation using separate cohorts of 60 HCC and 60 LC patients, with an accuracy of 83% for HCC and 92% for LC patients. The diagnostic odd ratio (DOR) indicated that SELDI-TOF proteomic signature could achieve better diagnostic performance than serum AFP level at a cutoff of 20 ng/mL (AFP20) (92.72 vs 9.11), particularly superior for early-stage HCC (87% vs 54%). Importantly, a combined use of both tests could enhance the detection of HCC (sensitivity, 95%; specificity, 98%; DOR, 931).ConclusionSerum SELDI-TOF proteomic signature, alone or in combination with AFP marker, promises to be a good tool for early diagnosis and/screening of HCC in at-risk population with liver cirrhosis.

Serum Biomarkers Identification by Mass Spectrometry in High-Mortality Tumors

“…The 3892 peak was considered as a complementary diagnostic marker or a potential marker for positive or negative α -fetoprotein HCC. SELDI-TOF analysis of sera from 120 patients affected by HCC and 120 affected by cirrhosis showed five proteomic peaks ( m / z 3324, 3994, 4665, 4795, and 5152) able to achieve, especially for early stage HCC, a diagnostic value better than serum AFP (83% sensitivity and 92% specificity in the test set) [100]. Cui et al [101] formulated classification trees, based on SELDI serum protein profiles, able to distinguish patients affected by chronic hepatitis B, cirrhosis, and HCC from healthy individuals.…”

Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

“…Transforming growth factor-beta1 (TGF-β1) and serum vimentin have also been proposed as potential biomarkers for small-sized HCC tumors [16], [17]. Serum SELDI-TOF proteomic signature, alone or in combination with AFP marker, may also be a promising tool for HCC screening in an at-risk population with liver cirrhosis due to its high sensitivity and specificity [18]. In separate reports, serum glypican-3 and human telomerase reverse transcriptase (hTERT) mRNA were also found to be increased in patients with HCC [19], [20].…”

Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment

“…Cytokeratin 19 (CYFRA21-1) is another useful tumor marker employed in the diagnosis of various types of cancer (13)(14)(15), and is particularly sensitive in adenocarcinomas in the gastrointestinal tract and pancreas (13,16 (2,17). Combined with ultrasonography, AFP is the most common clinical approach to diagnosing hepatocellular carcinoma (18). Serum carbohydrate antigen-125 (CA-125) and carbohydrate antigen-19.9 (CA-19.9) are also commonly used biomarkers in the screening of various types of cancer (19)(20)(21), and are particularly sensitive to cancer in the digestive system (22)(23)(24).…”