Proteomic analysis of laser-microdissected paraffin-embedded tissues: (1) Stage-related protein candidates upon non-metastatic lung adenocarcinoma

Kawamura, Takeshi; Nomura, Masatoshi; Tojo, Hiromasa; Fujii, Kiyonaga; Hamasaki, Hidehisa; Mikami, Sayaka; Bando, Yoshio; Kato, Harubumi; Nishimura, Toshihide

doi:10.1016/j.jprot.2009.11.011

Cited by 83 publications

(88 citation statements)

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“…Many researchers have applied quantitative proteomic approaches or combined proteomic and genomic analyses for the systematic discovery of potential lung cancer biomarkers (13,14,(22)(23)(24)(25). We compared the 133 potential lung cancer biomarkers identified in the current study with six lung cancer biomarker-related proteome data sets.…”

Section: Discussionmentioning

confidence: 99%

“…An alternative strategy for biomarker discovery is the use of tissue specimens, which may both reflect the progression of cancers in vivo and serve as prognostic markers. Several groups have successfully used tissue proteomic technologies to identify potential biomarkers in lung cancer (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Recently, Kikuchi et al performed an in-depth proteomic analysis of 3621 proteins from squamous cell carcinoma and ADC tissues using label-free quantitative proteomic approaches (14).…”

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confidence: 99%

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Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma

Hsu

Hsueh

et al. 2016

Molecular & Cellular Proteomics

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Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression. Molecular & Cellular Proteomics 15:

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma

Hsu

Hsueh

et al. 2016

Molecular & Cellular Proteomics

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“…and has been used in previous studies investigating novel diagnostic biomarkers (29)(30)(31)(32)(33)(34). Using semi-quantitative methods based on spectral counting, various proteins whose expression levels had changed by >2-fold were successfully identified in the lenses of STZ rats.…”

Section: Spectral Counting ------------------------------------------mentioning

confidence: 99%

Proteomic profile of the lens in a streptozotocin-induced diabetic rat model using shotgun proteomics

et al. 2017

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Abstract. Streptozotocin (STZ)-induced diabetic rats (STZ rats) were used to investigate diabetic cataracts. In the current study, a shotgun liquid chromatography (LC)/mass spectrometry (MS)-based global proteomic analysis method was used to examine the mechanism of lens opacification as a result of hyperglycemia in STZ rats. The 6-week old Wistar rats were injected with STZ for 2 days (100 mg/kg/day, i.p.) and housed for 3 weeks. The plasma glucose levels were identified to be significantly higher when compared with the normal rats and insulin was not detected in the STZ rats. Furthermore, opacification of the cortical epithelium was observed in the lenses of STZ rats. A total of 235 proteins were identified in the lenses of the STZ rats and 229 in the lenses of the normal rats. A label-free semi-quantitative method, based on spectral counting, identified 52 proteins that were differentially expressed in the lenses of STZ rats compared with normal rats. In particular, superoxide dismutase, which is a critical antioxidant enzyme that detoxifies superoxide through redox cycling, was downregulated when analyzed by the semi-quantitative method. In addition, phosphorylated-p38, which is important in the signaling pathway involved in the oxidative stress response, was significantly increased in the lenses of STZ rats when compared with normal rats (P<0.05). Thus, the changes in protein expression were evaluated in the lenses of STZ rats using a shotgun LC/MS-based global proteomic analysis approach, and a decrease in antioxidant enzymes and an increase in oxidative stress were identified in the lenses of STZ rats. Further studies are required to examine the role of these proteins in the onset or progression of diabetic cataracts. IntroductionDiabetes mellitus is one of the most severe types of metabolic disorder in humans globally, and is characterized by insulin resistance and impaired insulin secretion (1). Long-term hyperglycemia in diabetics leads to many complications with tissues that require insulin for glucose entrance or with insulin-independent organs (2), and cataracts are one of the most common complications of exposure to uncontrolled chronic hyperglycemia in diabetes. It has been reported that the onset of cataracts in diabetic patients is 20 years earlier than in non-diabetic subjects (3).Activation of the polyol pathway (4), non-enzymatic glycation of lens proteins (5-8) and increased oxidative stress (9-13) were reported as pathogenetic mechanisms of diabetic cataracts. In the polyol pathway, the excess glucose changes to sorbitol via aldose reductase and the excessive accumulation of sorbitol in the crystalline lens produces a high osmotic gradient, and causes the collapse and liquefaction of lens fibers, resulting in cataract formation (14,15). Furthermore, enhanced osmotic stress leads to the production of reactive oxygen species (ROS) in the crystalline lens (16)(17)(18). In addition, sorbitol is metabolized to fructose. The fructose is metabolized into fructose-3-phospate and 3-deoxyglucosone (p...

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“…4 The number of peptide spectra with moderate confidence was used as the spectral count value. Fold changes in expressed proteins at each area (WNT/Group 3 area) on a base-2 logarithmic scale were calculated using the protein ratio from spectral counting (Rsc).…”

Section: Semiquantitative Comparisons Using Spectral Countingmentioning

confidence: 99%

A patient with medulloblastoma in its early developmental stage

Shinojima¹,

Nakamura²,

Tasaki

et al. 2014

PED

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Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups— WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)—since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap—that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

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Proteomic analysis of laser-microdissected paraffin-embedded tissues: (1) Stage-related protein candidates upon non-metastatic lung adenocarcinoma

Cited by 83 publications

References 38 publications

Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma

Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma

Proteomic profile of the lens in a streptozotocin-induced diabetic rat model using shotgun proteomics

A patient with medulloblastoma in its early developmental stage

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