scholarly journals Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2000
Author(s):  
Hagen Kulbe ◽  
Oliver Klein ◽  
Zhiyang Wu ◽  
Eliane T. Taube ◽  
Wanja Kassuhn ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Operating Characteristic ◽  
Prognostic Markers ◽  
Early Stage ◽  
Imaging Mass Spectrometry ◽  
Maldi Imaging ◽  
High Grade ◽  
Proof Of Concept ◽  
Tissue Sections ◽  
Maldi Ims

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.

scholarly journals Discovery of prognostic markers for early-stage high-grade serous ovarian cancer by MALDI-Imaging

2020 ◽  
Author(s):  
H Kulbe ◽  
Z Wu ◽  
E Taube ◽  
W Kassuhn ◽  
S Darb-Esfahani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Markers ◽  
Early Stage ◽  
Maldi Imaging ◽  
High Grade ◽  
Serous Ovarian Cancer

MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma

2012 ◽  
Vol 75 (15) ◽  
pp. 4693-4704 ◽  
Author(s):  
Mareike Elsner ◽  
Sandra Rauser ◽  
Stefan Maier ◽  
Cédrik Schöne ◽  
Benjamin Balluff ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Prognostic Markers ◽  
Imaging Mass Spectrometry ◽  
Maldi Imaging ◽  
Barrett’S Adenocarcinoma ◽  
Maldi Imaging Mass Spectrometry

scholarly journals Serum Epiplakin Might Be a Potential Serodiagnostic Biomarker for Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5150
Author(s):  
Soichiro Shimura ◽  
Kazumasa Matsumoto ◽  
Yuriko Shimizu ◽  
Kohei Mochizuki ◽  
Yutaka Shiono ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Healthy Volunteers ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Early Stage ◽  
Area Under The Curve ◽  
Stone Disease ◽  
Dot Blot ◽  
Expression Levels ◽  
Clinicopathological Findings

Tumor markers that can be detected at an early stage are needed. Here, we evaluated the epiplakin expression levels in sera from patients with bladder cancer (BC). Using a micro-dot blot array, we evaluated epiplakin expression levels in 60 patients with BC, 20 patients with stone disease, and 28 healthy volunteers. The area under the curve (AUC) and best cut-off point were calculated using receiver-operating characteristic (ROC) analysis. Serum epiplakin levels were significantly higher in patients with BC than in those with stone disease (p = 0.0013) and in healthy volunteers (p < 0.0001). The AUC-ROC level for BC was 0.78 (95% confidence interval (CI) = 0.69–0.87). Using a cut-off point of 873, epiplakin expression levels exhibited 68.3% sensitivity and 79.2% specificity for BC. However, the serum epiplakin levels did not significantly differ by sex, age, pathological stage and grade, or urine cytology. We performed immunohistochemical staining using the same antibody on another cohort of 127 patients who underwent radical cystectomy. Univariate and multivariate analysis results showed no significant differences between epiplakin expression, clinicopathological findings, and patient prognoses. Our results showed that serum epiplakin might be a potential serodiagnostic biomarker in patients with BC.

scholarly journals Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry

2017 ◽  
Vol 22 (10) ◽  
pp. 1218-1228 ◽  
Author(s):  
E. Ellen Jones ◽  
Wujuan Zhang ◽  
Xueheng Zhao ◽  
Cristine Quiason ◽  
Stephanie Dale ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gaucher Disease ◽  
Imaging Mass Spectrometry ◽  
Maldi Imaging ◽  
Differential Signal ◽  
Esi Ms ◽  
Maldi Ims ◽  
Imaging Results ◽  
Hematoxylin And Eosin ◽  
And Control

To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

scholarly journals Pathfast Presepsin Assay for Early Diagnosis of Systemic Inflammatory Response Syndrome in Patients with Nephrolithiasis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yan-song Hou ◽  
Hua Wang ◽  
Hao Chen ◽  
Ling-feng Wu ◽  
Lin-feng Lu ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Operating Characteristic ◽  
Diagnostic Marker ◽  
Early Stage ◽  
Diagnostic Value ◽  
Bacterial Sepsis ◽  
Diagnostic Ability ◽  
Highly Sensitive ◽  
Comparable Performance ◽  
Median Plasma

It is relatively difficult to diagnose bacterial sepsis in nephrolithiasis patients. The aim of the study is to evaluate the diagnostic ability of presepsin in the differential diagnosis including SIRS, infection, or sepsis and to compare its diagnostic value with other markers, mainly as CRP, procalcitonin (PCT), and white blood cell (WBC) in patients of nephrolithiasis presenting with SIRS. 39 patients of nephrolithiasis who were diagnosed as SIRS were prospectively investigated. Plasma presepsin was detected by Pathfast presepsin assay system; CRP and PCT were measured as well. Additionally, 25 nephrolithiasis patients without SIRS were included. At all timing samples, patients were classified as SIRS or non-SIRS group. Median plasma presepsin levels were significantly increased in the SIRS group compared with non-SIRS group (452 pg/mL versus 178 ng/mL,P<0.001), and presepsin was markedly elevated even in the early stage of SIRS (584 pg/mL 6 h, 660 pg/mL 24 h versus 452 pg/mL,P<0.001). According to the receiver-operating characteristic (ROC) analysis, presepsin demonstrated a high diagnostic value compared with either PCT or CRP. In the early stage of SIRS, presepsin remained a highly sensitive (74.7%) and specific (88.4%) diagnostic marker compared with either PCT, CRP, or WBC. Moreover, the areas under the curve (AUCs) of presepsin (84.6%) were also superior to those seen in either PCT (79.6%) or CRP (71.8%). Thus plasma presepsin levels have comparable performance in SIRS for patients with nephrolithiasis.

scholarly journals Enhancement of Tryptic Peptide Signals from Tissue Sections using MALDI IMS Post-ionization (MALDI-2)

2021 ◽  
Author(s):  
Josiah McMillen ◽  
Danielle B. Gutierrez ◽  
Audra M. Judd ◽  
Jeffrey Spraggins ◽  
Richard M. Caprioli
Keyword(s):  
Imaging Mass Spectrometry ◽  
Human Kidney ◽  
Tissue Homogenate ◽  
Laser Desorption Ionization ◽  
Tissue Sections ◽  
Enhanced Sensitivity ◽  
Maldi Ims ◽  
Peptide Database ◽  
Peptide Signals

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) allows for highly multiplexed, unlabeled mapping of analytes from tissue sections. However, further work is needed to improve sensitivity and depth of coverage for protein and peptide IMS. Laser-based post-ionization MALDI-2 has been shown to increase sensitivity for several molecular classes but thus far this has not been reported for peptides. Here, we demonstrate signal enhancement of proteolytic peptides from thin tissue sections of human kidney by conventional MALDI (termed MALDI-1), and conventional MALDI augmented using a second ionizing laser (termed MALDI-2). Proteins were digested <i>in situ</i> using trypsin prior to IMS analysis. For identification of peptides and proteins, a tissue homogenate was analyzed by LC-MS/MS for bottom-up proteomics and the corresponding proteins identified. These proteins were next fully ‘digested <i>in silico’</i> to generate a database of theoretical peptides to then match to MALDI IMS datasets. Peptides were tentatively identified by matching the MALDI peak list to the database peptide list employing a 5 ppm error window. This resulted in 314 ± 45 (n=3) peptides and 1 112 ± 84 (n=3) peptides for MALDI-1 and MALDI-2, respectively. Protein identifications were similarly made by linking IMS data to the LC-MS/MS peptide database. With positive protein identifications requiring two or more peptides per protein, 55 ± 13 proteins were identified with MALDI-1 and 205 ± 10 with MALDI-2. These results demonstrate that MALDI-2 provides enhanced sensitivity for the spatial mapping of tryptic peptides and significantly increases the number of proteins identified in IMS experiments.<br>

Ionic Matrix for Enhanced MALDI Imaging Mass Spectrometry for Identification of Phospholipids in Mouse Liver and Cerebellum Tissue Sections

2010 ◽  
Vol 82 (21) ◽  
pp. 8800-8806 ◽  
Author(s):  
Kamlesh Shrivas ◽  
Takahiro Hayasaka ◽  
Naoko Goto-Inoue ◽  
Yuki Sugiura ◽  
Nobuhiro Zaima ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Liver ◽  
Imaging Mass Spectrometry ◽  
Maldi Imaging ◽  
Tissue Sections ◽  
Maldi Imaging Mass Spectrometry ◽  
Ionic Matrix

scholarly journals Enhancement of Tryptic Peptide Signals from Tissue Sections using MALDI IMS Post-ionization (MALDI-2)

2021 ◽  
Author(s):  
Josiah McMillen ◽  
Danielle B. Gutierrez ◽  
Audra M. Judd ◽  
Jeffrey Spraggins ◽  
Richard M. Caprioli
Keyword(s):  
Imaging Mass Spectrometry ◽  
Human Kidney ◽  
Tissue Homogenate ◽  
Laser Desorption Ionization ◽  
Tissue Sections ◽  
Enhanced Sensitivity ◽  
Maldi Ims ◽  
Peptide Database ◽  
Peptide Signals

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) allows for highly multiplexed, unlabeled mapping of analytes from tissue sections. However, further work is needed to improve sensitivity and depth of coverage for protein and peptide IMS. Laser-based post-ionization MALDI-2 has been shown to increase sensitivity for several molecular classes but thus far this has not been reported for peptides. Here, we demonstrate signal enhancement of proteolytic peptides from thin tissue sections of human kidney by conventional MALDI (termed MALDI-1), and conventional MALDI augmented using a second ionizing laser (termed MALDI-2). Proteins were digested <i>in situ</i> using trypsin prior to IMS analysis. For identification of peptides and proteins, a tissue homogenate was analyzed by LC-MS/MS for bottom-up proteomics and the corresponding proteins identified. These proteins were next fully ‘digested <i>in silico’</i> to generate a database of theoretical peptides to then match to MALDI IMS datasets. Peptides were tentatively identified by matching the MALDI peak list to the database peptide list employing a 5 ppm error window. This resulted in 314 ± 45 (n=3) peptides and 1 112 ± 84 (n=3) peptides for MALDI-1 and MALDI-2, respectively. Protein identifications were similarly made by linking IMS data to the LC-MS/MS peptide database. With positive protein identifications requiring two or more peptides per protein, 55 ± 13 proteins were identified with MALDI-1 and 205 ± 10 with MALDI-2. These results demonstrate that MALDI-2 provides enhanced sensitivity for the spatial mapping of tryptic peptides and significantly increases the number of proteins identified in IMS experiments.<br>

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