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- Urbiola-Salvador, Victor, et al.
(author)
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Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation
- 2024
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In: Biomarker Insights. - : Sage Publications. - 1177-2719. ; 19
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Journal article (peer-reviewed)abstract
- Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
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- Urbiola-Salvador, Victor, et al.
(author)
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Plasma protein changes reflect colorectal cancer development and associated inflammation
- 2023
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In: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 13
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Journal article (peer-reviewed)abstract
- Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed.Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few mu L of plasma sample.Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon gamma (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC.Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.
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3. |
- Filipowicz, Natalia, et al.
(author)
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Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4
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Journal article (peer-reviewed)abstract
- The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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4. |
- Stankowska, Wiktoria, et al.
(author)
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Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium
- 2024
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In: Cancers. - : MDPI. - 2072-6694. ; 16:5
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Journal article (peer-reviewed)abstract
- Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.
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- Vetrano, Davide L., et al.
(author)
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Health determinants and survival in nursing home residents in Europe : Results from the SHELTER study
- 2018
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In: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 107, s. 19-25
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Journal article (peer-reviewed)abstract
- Objective: The care processes directed towards institutionalized older people needs to be tailored on goals and priorities that are relevant for this specific population. The aim of the present study was (a) to describe the distribution of selected health determinants in a sample of institutionalized older adults, and (b) to investigate the impact on survival of such measures. Design: Multicentre longitudinal cohort-study. Setting: 57 nursing homes (NH) in 7 EU countries (Czech Republic, England, Finland, France, Germany, Italy, The Netherlands) and 1 non-EU country (Israel). Participants: 3036 NH residents participating in the Services and Health for Elderly in Long TERm care (SHELTER) study. Measurements: We described the distribution of 8 health determinants (smoking habit, alcohol use, body mass index [BMI], physical activity, social participation, family visits, vaccination, and preventive visits) and their impact on 1-year mortality. Results: During the one-year follow up, 611 (20%) participants died. Overweight (HR 0.79; 95% C.I. 0.64-0.97) and obesity (HR 0.64; 95% C.I. 0.48-0.87) resulted associated with lower mortality then normal weight. Similarly, physical activity (HR 0.67; 95% C.I. 0.54-0.83), social activities (HR 0.63; 95% C.I. 0.51-0.78), influenza vaccination (HR 0.66; 95% C.I. 0.55-0.80) and pneumococcal vaccination (HR 0.76 95% C.I. 0.63-0.93) were associated with lower mortality. Conversely, underweight (HR 1.28; 95% C.I. 1.03-1.60) and frequent family visits (HR 1.75; 95% C.I. 1.27-2.42) were associated with higher mortality. Conclusions: Health determinants in older NH residents depart from those usually accounted for in younger and fitter populations. Ad hoc studies are warranted in order to describe other relevant aspects of health in frail older adults, with special attention on those institutionalized, with the ultimate goal of improving the quality of care and life.
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