Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy

Abstract

Although postoperative adjuvant chemotherapy (PAC) with uracil -tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil -tegafur. However, we were unable to select responders to uracil -tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.

Synuclein-γ Is Closely Involved in Perineural Invasion and Distant Metastasis in Mouse Models and Is a Novel Prognostic Factor in Pancreatic Cancer

“…The resulting small peptide mixture (1 Ag) was analyzed using a liquid chromatography -tandem mass spectrometry (MS/MS) system in a fully automated manner (10,11). A reversed-phase peptide separation was done on a C18 capillary column (Michrom Bioresources) at a flow rate of 1 AL/min.…”

Identification by Differential Tissue Proteome Analysis of Talin-1 as a Novel Molecular Marker of Progression of Hepatocellular Carcinoma

“…The resected tissues were homogenized, and the homogenates were fractionated into phosphate-buffered saline (PBS) soluble and insoluble fractions [8]. An aliquot (50 µg protein) of the soluble fraction was subjected to tryptic hydrolysis in a polyacrylamide gel matrix [8,9].…”

Oncoproteomic Approaches in Lung Cancer Research

“…Specific isoforms of the CKs were associated with unfavourable prognosis, CYFRA21-1 was a more accurate diagnostic marker, and CK18 was a stronger prognostic factor (65). Other cytoskeletal proteins found to be correlated with a poor prognosis in lung adenocarcinoma are non-muscle myosin IIA and vimentin proteins, involved in epithelial-mesenchymal transition, a process at the basis of invasive and metastatic behaviour (66). Phosphohistidine phosphatase (PHP14) was proposed to be another lung cancer prognostic biomarker, regulating cell migration and invasion by cytoskeleton rearrangement.…”