scholarly journals Proteome biology of primary colorectal carcinoma and corresponding liver metastases

2021 ◽  
Author(s):  
Matthias Fahrner ◽  
Peter Bronsert ◽  
Stefan Fichtner-Feigl ◽  
Andreas Jud ◽  
Oliver Schilling
Keyword(s):  
Liver Metastases ◽  
Cell Junction ◽  
Cytoskeleton Organization ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Proteomic Investigation ◽  
Broad Variety ◽  
Tissue Specimens ◽  
Colorectal Adenocarcinomas

AbstractColorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.

Correlative Study of Microvessel Density and 5-Lipoxygenase Expression in Human Sporadic Colorectal Cancer

2008 ◽  
Vol 132 (11) ◽  
pp. 1807-1812
Author(s):  
Valeria Barresi ◽  
Enrica Vitarelli ◽  
Giovanni Tuccari ◽  
Gaetano Barresi
Keyword(s):  
Colorectal Cancer ◽  
Microvessel Density ◽  
Sporadic Colorectal Cancer ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Metabolizing Enzyme ◽  
Colorectal Adenocarcinomas ◽  
Positive Significant Correlation ◽  
Formalin Fixed

Abstract Context.—5-Lipoxygenase (5-LO) is an arachidonic acid– metabolizing enzyme, which has been demonstrated to exert a role in colorectal cancer tumorigenesis. Its activity in promoting neoangiogenesis in colorectal malignancies has been also recently theorized on the basis of in vitro studies. Objective.—To investigate whether any correlation existed between 5-LO immunoexpression amount and the quantity of neoangiogenesis, as reflected by microvessel density (MVD) in human sporadic surgically resected colorectal adenocarcinomas. Design.—A total of 45 formalin-fixed, paraffin-embedded colorectal adenocarcinomas were submitted to the immunohistochemical procedures for 5-LO and CD105, which represent specific markers for neoangiogenesis and which were used in the assessment of MVD. Results.—CD105-positive, intratumoral, newly formed vessels were present in 45 of 45 cases with variable MVD values. A 5-LO–positive immunohistochemical reaction was also found in 45 of 45 cases. A significantly higher MVD was evident in cases displaying a high 5-LO amount in comparison with those characterized by a low 5-LO expression (28.33 vs 19.44 vessels per mm2; P = .02). In addition, a positive significant correlation emerged between 5-LO immunoexpression amount and the MVD counts (r = 0.2986, P = .04). Conclusions.—Our study demonstrates the existence of a relationship between 5-LO expression and the neoangiogenesis process as reflected by intratumoral MVD in human sporadic colorectal adenocarcinomas, thus suggesting that 5-LO may modulate the formation of blood vessels in these neoplasias.

scholarly journals Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays

2016 ◽  
Vol 54 (11) ◽  
pp. 2798-2803 ◽  
Author(s):  
Elham Salehi ◽  
Mohammad T. Hedayati ◽  
Jan Zoll ◽  
Haleh Rafati ◽  
Maryam Ghasemi ◽  
...  
Keyword(s):  
Fusarium Oxysporum ◽  
Aspergillus Flavus ◽  
Ffpe Tissue ◽  
Content Type ◽  
Real Time Quantitative Pcr ◽  
Tissue Sections ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tissue Specimens ◽  
Formalin Fixed

In a retrospective multicenter study, 102 formalin-fixed paraffin-embedded (FFPE) tissue specimens with histopathology results were tested. Two 4- to 5-μm FFPE tissue sections from each specimen were digested with proteinase K, followed by automated nucleic acid extraction. Multiple real-time quantitative PCR (qPCR) assays targeting the internal transcribed spacer 2 (ITS2) region of ribosomal DNA, using fluorescently labeled primers, was performed to identify clinically important genera and species of Aspergillus , Fusarium , Scedosporium , and the Mucormycetes . The molecular identification was correlated with results from histological examination. One of the main findings of our study was the high sensitivity of the automated DNA extraction method, which was estimated to be 94%. The qPCR procedure that was evaluated identified a range of fungal genera/species, including Aspergillus fumigatus , Aspergillus flavus , Aspergillus terreus , Aspergillus niger , Fusarium oxysporum , Fusarium solani , Scedosporium apiospermum , Rhizopus oryzae , Rhizopus microsporus , Mucor spp., and Syncephalastrum . Fusarium oxysporum and F. solani DNA was amplified from five specimens from patients initially diagnosed by histopathology as having aspergillosis. Aspergillus flavus , S. apiospermum , and Syncephalastrum were detected from histopathological mucormycosis samples. In addition, examination of four samples from patients suspected of having concomitant aspergillosis and mucormycosis infections resulted in the identification of two A. flavus isolates, one Mucor isolate, and only one sample having both R. oryzae and A. flavus . Our results indicate that histopathological features of molds may be easily confused in tissue sections. The qPCR assay used in this study is a reliable tool for the rapid and accurate identification of fungal pathogens to the genus and species levels directly from FFPE tissues.

scholarly journals Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 863 ◽  
Author(s):  
Eline Berghmans ◽  
Julie Jacobs ◽  
Christophe Deben ◽  
Christophe Hermans ◽  
Glenn Broeckx ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Immune Response ◽  
Cancer Cells ◽  
Mass Spectrometry Imaging ◽  
Predictive Biomarker ◽  
Protein Biomarkers ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Nsclc Patients

(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC. These results were verified and confirmed with immunohistochemical analyses. In addition, we provide in-vitro evidence of the immune stimulatory effect of neutrophil defensins towards cancer cells; and (4) Conclusions: With proteomic approaches, we have discovered neutrophil defensins as additional prospective biomarkers for an anti-PD-(L)1 immunotherapy response. Thereby, we also demonstrated that the neutrophil defensins contribute in the activation of the immune response towards cancer cells, which could provide a new lead towards an anticancer therapy.

scholarly journals Improved RT-PCR Amplification for Molecular Analyses with Long-term Preserved Formalin-fixed, Paraffin-embedded Tissue Specimens

2006 ◽  
Vol 54 (7) ◽  
pp. 773-780 ◽  
Author(s):  
Kiyohiro Hamatani ◽  
Hidetaka Eguchi ◽  
Keiko Takahashi ◽  
Kazuaki Koyama ◽  
Mayumi Mukai ◽  
...  
Keyword(s):  
Pcr Amplification ◽  
Rt Pcr ◽  
Molecular Analyses ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tissue Specimens ◽  
Formalin Fixed
Sign in / Sign up

Export Citation Format

Share Document