Peptide Signatures for Prognostic Markers of Pancreatic Cancer by MALDI Mass Spectrometry Imaging

Abstract

Despite the overall poor prognosis of pancreatic cancer there is heterogeneity in clinical courses of tumors not assessed by conventional risk stratification. This yields the need of additional markers for proper assessment of prognosis and multimodal clinical management. We provide a proof of concept study evaluating the feasibility of Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify specific peptide signatures linked to prognostic parameters of pancreatic cancer. On 18 patients with exocrine pancreatic cancer after tumor resection, MALDI imaging analysis was performed additional to histopathological assessment. Principal component analysis (PCA) was used to explore discrimination of peptide signatures of prognostic histopathological features and receiver operator characteristic (ROC) to identify which specific m/z values are the most discriminative between the prognostic subgroups of patients. Out of 557 aligned m/z values discriminate peptide signatures for the prognostic histopathological features lymphatic vessel invasion (pL, 16 m/z values, eight proteins), nodal metastasis (pN, two m/z values, one protein) and angioinvasion (pV, 4 m/z values, two proteins) were identified. These results yield proof of concept that MALDI-MSI of pancreatic cancer tissue is feasible to identify peptide signatures of prognostic relevance and can augment risk assessment.

MALDI-MSI: A Powerful Approach to Understand Primary Pancreatic Ductal Adenocarcinoma and Metastases

“…A study from Loch et al, where MALDI-MSI was used to investigate prognostic markers of lymphatic vessel invasion, lymph node metastasis, and angioinvasion in pancreatic cancer, it was determined that actin, COL2A1, COL4A3, filamin-B, histone H1.3, spectrin β-chain, non-erythrocytic, vasolin-containing protein, and vinculin are peptide signatures of lymphatic vessel invasion; COL2A1 and myosin-11 were identified as prognostic signatures of angioinvasion; and histone 1.3 was associated with lymph node metastases [ 25 ]. These results portray the pivotal role of collagens in the progression of pancreatic malignancies.…”

MALDI Mass Spectrometry Imaging for the Distinction of Adenocarcinomas of the Pancreas and Biliary Tree

“…Further studies are definitely needed to unravel the complex interactions in extracellular matrix formation, nonetheless, it is clear that collagens are essential components in the pathogenesis of PDAC. Besides different types of collagens, variants of the structural protein actin were shown to be differentially expressed in pancreatic carcinomas with or without lymphatic vessel invasion (actin/cytoplasmic 1 and collagen alpha-2(I) chain), as well as pancreatic carcinomas, with and without blood vessel invasion (collagen alpha-2(I) chain) [ 26 ]. All these reports underline the assumption that the discriminative features found here indeed hold a biological significance.…”

Advanced progress of spatial metabolomics in head and neck cancer research

“…Florian N Loch et al. [102] successfully employed MALDI-MSI to discern specific peptides significantly associated with adverse prognostic parameters, including lymphatic vascular invasion (pL), lymph node metastasis (pN), and vascular invasion (pV, p < 0.001), in pancreatic cancer patients. This study exemplifies the feasibility of MALDI-MSI in identifying peptide signatures corresponding to prognostic indicators of pancreatic cancer.…”