RESUMO
Blood tests are needed to aid in the early detection of pancreatic ductal adenocarcinoma (PDAC), and monitoring pancreatitis development into malignancy especially in high risk patients. This study exhibits efforts and progress toward developing such blood tests, using electrospray-mass spectrometry (MS) serum profiling to distinguish patients with early-stage PDAC or pancreatitis from each other and from controls. Identification of significant serum mass peak differences between these individuals was performed using t tests and "leave one out" cross validation. Serum mass peak distributions of control individuals were distinguished from those of patients with chronic pancreatitis or early-stage PDAC with P values <10(-15), and patients with chronic pancreatitis were distinguished from those of patients with early-stage PDAC with a P value <10(-12). Sera from 12 out of 12 patients with PDAC stages I, IIA and IIB were blindly validated from controls. Tandem MS/MS identified a cancer phenotype with elements of PDAC involved in early-stage PDAC/control discrimination. These studies indicate electrospray-MS mass profiling can detect serum changes in patients with pancreatitis or early-stage pancreatic cancer. Such technology has the potential to aid in early detection of pancreatic cancer, biomarker development, and in monitoring development of pancreatitis into PDAC.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/sangue , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Neoplasias Pancreáticas/sangue , Pancreatite Crônica/sangue , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
The goal of this study was to evaluate the usefulness of electrospray ionization-mass spectrometry (ESI-MS) technology to distinguish sera of early-stage lung cancer patients from control individuals. ESI-MS m/z (mass divided by charge) data were generated from sera of 43 non-small cell lung cancer patients (pathological stages I and II) and 21 control individuals. Identifications of m/z peak area significances between cancer and control ESI-MS sera spectra were performed using t-tests. A "leave one out" cross validation procedure, which mimics blinded sera analysis and corrects for "over-fitting" of data, yielded discriminatory cancer versus control distribution p value and ROC curve area value of <0.001 and 0.87, respectively. Analysis without the "leave one out" cross validation procedure yielded a ROC curve area of 0.99 for discrimination of sera from lung cancer patients versus control individuals. Predictive value measurements revealed overall test efficiency and sensitivity for distinguishing sera from lung cancer patients from controls (using "leave one out" cross validation) of 80% and 84%, respectively. ESI-MS serum analysis between control individuals and lung cancer patients who smoked or did not smoke had p values in ranges indicating that smoking effects are not pronounced in our analysis. These studies indicate that ESI-MS analyses of sera from early stage non-small cell lung cancer patients were helpful in distinguishing these patients from control individuals.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Espectrometria de Massas por Ionização por Electrospray , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Diagnóstico Diferencial , Detecção Precoce de Câncer , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e EspecificidadeRESUMO
This study evaluated the usefulness of electrospray mass spectrometry to distinguish sera of early-stage pancreatic cancer patients from disease-free individuals. Sera peak data were generated from 33 pancreatic cancer patients and 30 disease-free individuals. A "leave one out" cross-validation procedure discriminated stage I/II pancreatic cancer versus disease-free sera with a p value <.001 and a receiver-operator characteristic curve area value of 0.85. Predictive values for cancer stage I/II test efficiency, specificity, and sensitivity were 78%, 77%, and 79%, respectively. These studies indicate that electrospray mass spectrometry is useful for distinguishing sera of early-stage pancreatic cancer patients from disease-free individuals.