Analysis of ATP7A Expression and Ceruloplasmin Levels as Biomarkers in Patients Undergoing Neoadjuvant Chemotherapy for Advanced High-Grade Serous Ovarian Carcinoma

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10195 - 10195

Опубликована: Сен. 23, 2024

Ovarian cancer (OC), particularly high-grade serous carcinoma (HGSC), is a leading cause of gynecological mortality due to late diagnosis and chemoresistance. While studies on OC cell lines have shown that overexpression the ATP7A membrane transporter correlates with resistance platinum-based drugs (PtBMs) cross-resistance copper (Cu), clinical evidence lacking. The functionality ceruloplasmin (CP), main Cu-transporting protein in blood, dependent on, among other things, activity. This study investigated expression CP levels as potential biomarkers for predicting responses PtBMs. We included 28 HGSC patients who underwent neoadjuvant chemotherapy (NACT). ovarian peritoneal tissues before NACT omental after was analyzed via qPCR, ascites plasma were measured ELISA NACT. In total, 54% exhibited pretreatment tissue (ovary and/or peritoneum), while 43% treatment (peritoneum omentum). A significant association found between higher peritoneum an unfavorable CA-125 elimination rate constant k (KELIM) score. Patients had significantly mean Plasma decreased NACT, associated shorter platinum-free interval (PFI). These findings suggest serve predictive markers chemoresistance, but further research needed validate their utility.

Язык: Английский

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Speciation of copper in human serum using conjoint liquid chromatography on short-bed monolithic disks with UV and post column ID-ICP-MS detection

Journal of Analytical Atomic Spectrometry, Год журнала: 2022, Номер 37(8), С. 1675 - 1686

Опубликована: Янв. 1, 2022

A new method based on conjoint liquid chromatography with post-column ID-ICP-MS detection was developed for the speciation of Cu in human serum. ceruloplasmin (Cu-Cp) is suggested as a potential biomarker cancer diagnosis.

Язык: Английский

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Decreased TMPRSS2 expression by SARS-CoV-2 predicts the poor prognosis of lung cancer patients through metabolic pathways and immune infiltration

Aging, Год журнала: 2022, Номер 14(1), С. 73 - 108

Опубликована: Янв. 11, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world and became a global pandemic in 2020. One promising drug target for SARS-CoV-2 is transmembrane protease serine (TMPRSS2). This study was designed to explore expression status, prognostic significance molecular functions of TMPRSS2 lung cancer. investigated using TIMER, Oncomine, UALCAN, GEO, HPA TCGA databases. The value examined Cox regression nomogram. KEGG, GO GSEA were performed investigate cellular function relationship between immune infiltration determined TIMER CIBERSORT algorithms. mRNA protein significantly reduced Decreased increased DNA methylation associated with various clinicopathological parameters patients Low also correlated poor outcome cancer patients. Moreover, nomogram constructed exhibited good predictive power overall survival KEGG analyses implied that multiple immune- metabolism-related pathways linked expression. Intriguingly, cell More importantly, markedly decreased SARS-CoV-infected cells. These findings indicate may be biomarker therapeutic through metabolic infiltration.

Язык: Английский

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Novel Cuproptosis-Related Gene Signature for Precise Identification of High-Risk Populations in Low-Grade Gliomas

Mediators of Inflammation, Год журнала: 2023, Номер 2023, С. 1 - 12

Опубликована: Фев. 13, 2023

Patients with low-grade glioma (LGG) have wildly varying average lifespans. However, no effective way exists for identifying LGG patients at high risk. Cuproptosis is a recently described form of cell death associated the abnormal aggregation lipid acylated proteins. Few investigations been conducted on cuproptosis-associated genes and thus far. The purpose this research to establish predictive model cuproptosis-related in order recognise populations risk.We analyzed 926 LGGs from 2 public datasets, all which were RNA sequencing datasets. On basis immune scores, population was split into different risk categories X-tile. LASSO Cox regressions employed filter construct prediction models. accuracy models measured by using TCGA internal validation set CGGA external set. In addition, infiltration viewed CIBERSORT ssGSEA algorithms correlation analysis done genes. Finally, escape capacity low- high-risk groups evaluated TIDE method.The constructed four used identify LGG. It performed well training sets (AUC values: 0.915, 0.894, 0.774). Meanwhile, we found that FDX1 ATP7A positively correlated response, while GCSH ATP7B opposite. score group had lower score, indicating their weak.High-risk individuals can be reliably identified based Furthermore, cuproptosis closely related tumor microenvironment, gives novel approach treating

Язык: Английский

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Inflammation-Associated Cytotoxic Agents in Tumorigenesis

Cancers, Год журнала: 2023, Номер 16(1), С. 81 - 81

Опубликована: Дек. 22, 2023

Chronic inflammatory processes are related to all stages of tumorigenesis. As inflammation is closely associated with the activation and release different cytotoxic agents, interplay between agents antagonizing principles highlighted in this review address question how tumor cells overcome enhanced values tumors. In cells, formation mitochondrial-derived reactive species elevated iron ions free heme antagonized by an overexpression enzymes proteins, contributing antioxidative defense maintenance redox homeostasis. Through these mechanisms, can even survive additional stress caused radio- chemotherapy. secretion active from immune suppressed microenvironment extracellular matrix components induced. Different oxidant- protease-based involved tumor-mediated immunosuppression, growth, cell invasion, metastasis. Considering special metabolic conditions tumors, main focus here was directed on disturbed balance protective mechanisms late-stage This knowledge mandatory for implementation novel anti-cancerous therapeutic approaches.

Язык: Английский

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Identification of Hypoxia Prognostic Signature in Glioblastoma Multiforme Based on Bulk and Single-Cell RNA-Seq

Cancers, Год журнала: 2024, Номер 16(3), С. 633 - 633

Опубликована: Фев. 1, 2024

Glioblastoma (GBM) represents a profoundly aggressive and heterogeneous brain neoplasm linked to bleak prognosis. Hypoxia, common feature in GBM, has been tumor progression therapy resistance. In this study, we aimed identify hypoxia-related differentially expressed genes (DEGs) construct prognostic signature for GBM patients using multi-omics analysis. Patient cohorts were collected from publicly available databases, including the Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), The Cancer Atlas-Glioblastoma Multiforme (TCGA-GBM), facilitate comprehensive Hypoxia-related (HRGs) obtained Molecular Signatures Database (MSigDB). Differential expression analysis revealed 41 DEGs patients. A consensus clustering approach, utilizing these DEGs' patterns, identified four distinct clusters, with cluster 1 showing significantly better overall survival. Machine learning techniques, univariate Cox regression LASSO regression, delineated comprising six (ANXA1, CALD1, CP, IGFBP2, IGFBP5, LOX). Multivariate substantiated significance of set three optimal (CP, Using signature, classified into high- low-risk categories. Survival demonstrated that high-risk group exhibited inferior survival rates comparison group. showed good predictive performance, as indicated by area under curve (AUC) values one-, three-, five-year Furthermore, functional enrichment biological processes pathways associated hypoxia, providing insights underlying mechanisms GBM. Delving immune microenvironment, our correlations relating infiltration cells Overall, study highlights potential valuable resource forecasting outcome approach integrating bulk sequencing, single-cell analysis, microenvironment assessment enhances understanding intricate biology characterizing thereby potentially informing tailored design therapeutic interventions.

Язык: Английский

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Analysis of serum peptidome profiles of non-metastatic and metastatic feline mammary carcinoma using liquid chromatography-tandem mass spectrometry

BMC Veterinary Research, Год журнала: 2024, Номер 20(1)

Опубликована: Июнь 29, 2024

Abstract Background Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection essential for preventing local distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers monitoring disease progression in non-metastatic FMC (NmFMC) (mFMC) are limited. The objective of this study was to investigate serum peptidome profiles NmFMC mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional conducted compare 13 NmFMC, 23 18 healthy spectrometry analysis performed on non-trypsinized samples. Results Out total 8284 expressed proteins observed, several were found be associated with human breast cancer. In distinctive expressions encompassed double-stranded RNA-binding Staufen homolog 2 (STAU2), cell proliferation, along bromodomain adjacent zinc finger domain 2A (BAZ2A) gamma-aminobutyric acid type receptor subunit epsilon (GABRE), identified as treatment targets. Paradoxically, positive prognostic markers emerged, such complement C1q like 3 (C1QL3) erythrocyte membrane band 4.1 (EPB41 or 4.1R). Within group, overexpressed poor prognosis exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase (TXNRD3) ceruloplasmin (CP). Meanwhile, presence POU class 5 homeobox (POU5F1 OCT4) laminin alpha 1 (LAMA1), reported biomarkers, noted. Conclusion both pro- anti-proliferative potentially indicating characteristic NmFMC. Conversely, metastasis noted group.

Язык: Английский

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A novel ferroptosis‑related gene signature for overall survival prediction and immune infiltration in patients with breast cancer

International Journal of Oncology, Год журнала: 2022, Номер 61(6)

Опубликована: Окт. 12, 2022

Breast cancer is the most prevalent type of among women worldwide. The heterogeneous nature breast poses a serious challenge for prognostic prediction and individualized therapies. Recently, ferroptosis, an iron‑dependent form programmed cell death, has been reported to serve significant role in regulation biological behavior tumors. Several studies have revealed significance ferroptosis‑related gene (FRG) model; however, additional efforts are required elucidate details. Moreover, genes that modulate ferroptosis may be promising candidate bioindicators therapy. present study systematically assessed expression profiles FRGs reveal relationship between features patients with based on data obtained from Gene Expression Omnibus Molecular Taxonomy Cancer International Consortium. Using non‑negative matrix factorization clustering method, were classified into two sub‑groups (cluster 1 cluster 2) FRGs. Furthermore, Cox regression, least absolute shrinkage selection operator methods used construct risk score formula comprised nine genes, which stratified groups. Patients belonging high‑risk group exhibited significantly shorter overall survival (OS) time compared low‑risk group. value this signature was further verified training validation cohorts. results univariate multivariate regression analyses indicated acted as independent predictor OS. Subsequently, nomogram constructed. Receiver operating characteristic analysis confirmed resulting powerful discriminatory ability. Functional immune environment differed notably groups association proliferation, migration drug resistance. Taken together, demonstrated associated progression, thus could novel biomarkers treatment cancer.

Язык: Английский

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Nullomer peptide increases immune cell infiltration and reduces tumor metabolism in triple negative breast cancer mouse model

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Июнь 28, 2023

Abstract Background Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group species. Primes those nullomers that have not been detected genome any 9S1R is 5-aa peptide derived from prime sequence tagged with 5 arginine aa, used to treat triple negative breast cancer (TNBC) an vivo TNBC mouse model. administered trehalose (9S1R-NulloPT), which enhances solubility and exhibits some independent effects against tumor growth thus important component drug preparation. Method We examined effect 9S1R-NulloPT on growth, metabolism, metastatic burden, necrosis, immune microenvironment, transcriptome aggressive tumors. Results The peptide-treated mice had smaller tumors initial phase treatment, as compared untreated control, reduced bioluminescence at later stages, indicative metabolically inactive A decrease ex was also observed excised treated mice, but secondary metastasis lungs. treatment caused changes microenvironment increased infiltration cells margin inflammation. upregulated 365 genes downregulated 710 group. Consistent vitro findings cell lines, include Cellular Metabolic Process Related (179), specifically mitochondrial associated TCA cycle/oxidative phosphorylation (44), translation machinery/ribosome biogenesis (45). Among genes, Developmental Pathway (13), ECM Organization (12) Focal Adhesion Pathways (7) were noteworthy. present data pilot study using bilateral BC model, supports our findings. Conclusion In conclusion, although moderate reducing volume, it altered well transcriptome, rendering less active by downregulating function ribosome biogenesis. This corroborates previously published

Язык: Английский

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Validation of a Novel Cuproptosis–Related Prognostic Gene Marker and Differential Expression Associated with Lung Adenocarcinoma

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(10), С. 8502 - 8518

Опубликована: Окт. 22, 2023

Cuproptosis induction is seen as a promising alternative for immunotherapies and targeted therapies in breast cancer. The objective of this research was to examine the prognostic biological importance cuproptosis-related genes (CRGs) lung adenocarcinoma (LUAD).The following methods were used: GSE10072 dataset TCGA database analysis, differential expression analysis CRGs, function (BP) signaling pathway enrichment clinical construction signature RNA modified miRNA CRGs LUAD, immunoinfiltration immunohistochemical staining DβH, UBE2D3, SOD1, UBE2D1 LOXL2.AOC1, ATOX1, CCL8, CCS, COX11, CP, LOXL2, MAP2K2, PDK1, SCO2, UBE2D1, UBE2D3 VEGFA showed significantly higher expression, while ATP7B, PDE3B, SLC31A2, UBE2D2, UBE2D4 ULK2 lower LUAD tissues than normal tissues. We also found that ATP7B (4%), AOC1 (3%) PDE3B (2%), DβH CP (1%), PDK1 LOXL2 (1%) mutation frequencies. univariate Cox used identify have value. It identified 21 significant value, containing LOXL2. Patients with up-expression longer survival time patients down-expression time. hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-181c-5p, hsa-miR-1245a, etc., play an important role regulatory network, miR-29a, miR-29c miR-181c high longer, miR-1245a low longer. performed relationships between immune infiltration including B cells, CD8+ T CD4+ macrophages, neutrophils DCs.DβH, are potential candidates implicated can be further explored their application diagnostic, prognostic, therapeutic biomarkers LUAD.

Язык: Английский

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