Abstract
Biliary tract cancers (BTCs) are lethal malignancies currently lacking satisfactory methods for early detection and accurate diagnosis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a promising diagnostic tool for this disease. In this pilot study, sera samples from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a population-based case-control study were randomly grouped into training set (30 BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree classifier was built using the training set and applied to all test sets. The classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242 mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a specificity of 85.0% when comparing BTCs with non-cancers. When applied to the duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%, respectively. The agreement of the training and duplicate sets was 71.4% (Kappa = 0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates of one sample for the five differential peaks were 15.8–68.8% for intensity and 0–0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI-TOF-MS may be a promising approach for identifying BTCs but low assay reproducibility may limit its application in clinical practice.
Highlights
Biliary tract cancers (BTCs), encompassing tumors of gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but fatal malignancies
Fifty BTCs, 30 cholelithiasis and 30 healthy controls were randomly selected from the participants of the Shanghai Biliary Tract Cancer study (SBTCS), a population-based case-control study conducted by the Shanghai Cancer Institute and the National Cancer Institute between 1997 and 2001
By BTC sub-sites, 19 were gallbladder cancers, eight were extrahepatic bile duct cancers, and three were ampulla of Vater cancers; no significant difference in BTC types was observed between training set and blind test set (P for χ2 test = 0.99)
Summary
Biliary tract cancers (BTCs), encompassing tumors of gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but fatal malignancies. Due to the difficult accessibility of diagnostic tissues and lack of specific symptoms, most BTCs are often detected at an advanced stage, resulting in average 5-year relative survival rates of 10–20% [3]. Survival rates are closely related with stage at diagnosis. The 5-year survival rates were only 0.7% for gallbladder cancer and 1.3% for extrahepatic bile duct cancer with metastasis, compared to 41.9% and 26.5% for localized cancers, respectively [3]. Donohue et al [4] reported an after-surgery 5-year survival rate of less than 5% for gallbladder cancer in patients diagnosed at a later stage, but an 85%–91% rate for those diagnosed at an early stage. In a Chinese population, the survival rate of gallbladder cancer was closely associated with the stage at diagnosis [5]. Methods that could aid in early detection are desirable for better outcomes
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