Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry

Abstract

Purpose: Each year in the United States, ϳ 30,000 people die from pancreatic cancer. Fewer than 5% of patients survive >5 years after diagnosis, because most patients present with advanced disease. Early diagnosis may improve the prognosis of patients with pancreatic cancer.Experimental Design: In an attempt to improve on current approaches to the serological diagnosis of pancreatic cancer, we analyzed serum samples from patients with and without pancreatic cancer using surface-enhanced laser desorption and ionization (SELDI) protein chip mass spectrometry. Using a case-control study design, serum samples from 60 patients with resectable pancreatic adenocarcinoma were compared with samples from 60 age-and sex-matched patients with nonmalignant pancreatic diseases, as well as 60 age-and sex-matched healthy controls. To increase the number of proteins potentially identifiable, serum was fractionated using anion exchange and profiled on two ProteinChip surfaces (metal affinity capture and weak cation exchange).Results: We determined a minimum set of protein peaks able to discriminate between patient groups and used the unified maximum separability algorithm to compare the performance of the individual marker panels alone or in conjunction with CA19 -9. Among the peaks identified by SELDI profiling that had the ability to distinguish between patient groups, the 2 most discriminating protein peaks could differentiate patients with pancreatic cancer from healthy controls with a sensitivity of 78% and specificity of 97%. These 2 markers performed significantly better than the current standard serum marker, CA19 -9 (P < 0.05).The diagnostic accuracy of the 2 markers was improved by using them in combination with CA 19 -9. Similarly, a combination of 3 SELDI markers and CA19 -9 was superior to CA19 -9 alone in distinguishing individuals with pancreatic cancer from the combined pancreatic disease controls and healthy subject groups (P ‫؍‬ 0.078). SELDI markers were also better than CA19 -9 in distinguishing patients with pancreatic cancer from those with pancreatitis.Conclusion: SELDI profiling of serum can be used to accurately differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy controls.

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

“…The pooled coefficient of variance (pCV) for peak intensity was calculated for each experimental condition and had a mean of 22% (12-35%), in agreement with previous reports (Petricoin et al, 2002a, b;Koopmann et al, 2004;Zhang et al, 2004).…”

“…Consequently, serum may be an appropriate surrogate tissue to investigate since it may share the fingerprint of various physiologic or pathologic processes involving cancer tissue and/or host response (Fung et al, 2005). Coupled to appropriate bioinformatic tools, SELDI-TOF MS was recently shown as a very promising method for probing serum to identify protein patterns and/or biomarkers related to various stages and types of solid tumors (Adam et al, 2002a;Petricoin et al, 2002a, b;Koopmann et al, 2004;Wadsworth et al, 2004;Zhang et al, 2004), which could serve as early diagnostic markers.…”

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

“…There is a wide range of different data analysis approaches that could be applied to this type of mass spectrometric data, for example neural networks (NN) has successfully been applied to SELDI data (Ball et al, 2002;Liu et al, 2005) as well as support vector machines (SVM) (Koopmann et al, 2004) and hierarchical clustering (Poon et al, 2003). The data acquired in this study were analysed using the multivariate projection methods principal component analysis (PCA) and partial least squares -discriminant analysis (PLS-DA).…”

Protein nanotechnology — A powerful futuristic diagnostic technique

“…It is also applicable to study the proteinprotein interaction, the functional activity of proteins and in the discovery of disease markers and diagnosis (12,13). It can also be used for profiling of the serum to differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy control (16). Heart failure, arising from systemic disease or specific heart muscle disease, is one of the leading causes of morbidity and mortality in developing countries (4).…”