14 research outputs found
Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection
BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods
Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial–Mesenchymal Transition Induced with TGF‑β
The
epithelial-to-mesenchymal transition (EMT) is a unique process
for the phenotypic changes of tumor cells characterized by a transition
from polarized rigid epithelial cells to migrant mesenchymal cells,
thus conferring the ability of tumor invasion and metastasis. A major
challenge in the treatment of lung adenocarcinoma is to identify early
stage patients at a high risk of recurrence or metastasis, thereby
permitting the best therapeutic strategy and prognosis. In this study,
we used a transforming growth factor-β (TGF-β)-induced
EMT model to quantitatively identify protein tyrosine phosphorylation
during the course of EMT in relation to malignant characteristics
of lung adenocarcinoma cells. We performed relative quantitation analysis
of tyrosine-phosphorylated peptides in TGF-β-treated and -untreated
lung adenocarcinoma cells and identified tyrosine-phosphorylated proteins
that were upregulated in TGF-β-treated cells. These include
tensin-1 (TNS1) phosphorylated on Y1404, hepatocyte growth factor
receptor (c-Met) phosphorylated on Y1234, and NT-3 growth factor receptor
(TrkC) phosphorylated on Y516. We also found that these protein phosphorylation
profiles were specifically observed in tissue samples of patients
with poor prognostic lung adenocarcinoma. Tyrosine phosphorylations
of these proteins represent possible candidates of prognostic prediction
markers for lung adenocarcinoma
Proteomic Analysis of Proteins Related to Prognosis of Lung Adenocarcinoma
We attempted to identify prognosis-related
proteins expressed in
early resection lung adenocarcinomas that had higher metastatic potential.
Early resection of lung adenocarcinoma tissues were collected from
patients who experienced recurrence within 5 years after surgery;
these patients are defined here as the poor prognosis group. From
these samples, we prepared frozen tissue sections and then isolated
cancerous areas by laser capture microdissection to allow extraction
of cancer tissue-derived soluble proteins. Shotgun LC–MS/MS
analysis detected and identified a total of 875 proteins in these
cancer tissues. Relative quantitative analysis revealed that 17 proteins
were preferentially expressed in the poor prognosis group relative
to the good prognosis group, which consisted of patients who did not
exhibit recurrence. Among them, 14-3-3 beta/alpha and calnexin were
reported to be potentially involved in tumor recurrence and the malignant
properties of lung cancer. Here immunological analyses confirmed disease-associated
expression of these proteins. In a cell-culture model using A549,
targeted depletion of either 14-3-3 beta/alpha or calnexin reduced
proliferation, invasion, and migration, suggesting that both proteins
are involved in determining the malignant properties of lung cancer
that contribute to poor prognosis