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Withey K, Brougham MFH, Paciarotti I, McKenzie JM, Wilson DC, Revuelta Iniesta R. Associations of Ferritin and Folate Status With Clinical Outcomes in Childhood Cancer Patients: A Prospective Cohort Study. Pediatr Blood Cancer 2025; 72:e31645. [PMID: 40055871 DOI: 10.1002/pbc.31645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 02/04/2025] [Accepted: 02/22/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND Given the limited research on folate and ferritin status in children with cancer undergoing treatment, we investigated the prevalence of abnormalities and their impact on clinical outcomes and treatment complications. METHODS This prospective cohort study enrolled children <18 years diagnosed with cancer between August 2010 and February 2014. Data collection occurred at diagnosis, 3, 6, 9, 12 and 18 months. Clinical outcomes were classified as event-free survival or events (relapse, death, the development of new metastasis, becoming palliative) and treatment complications. Micronutrient status was assessed through clinical and nutritional analyses. Binary logistic regression, multilevel model analysis explored relationships between micronutrient status and clinical outcomes. RESULTS Eighty-two patients (median [interquartile range] 3.9 (1.9-8.8) years, 56% males) were recruited. Excess ferritin (85%) and folate deficiency (25.5%) were prevalent micronutrient abnormalities throughout the study. Decreased ferritin levels reduced the odds of events by 83.9% (odd ratios = 0.161, 95% CI = 1.000-1.002, p = 0.032). Higher ferritin was associated with increased number of treatment-related complications (B = 7.3E-5, 95% CI = 1.5E-5-0.000, p = 0.013). Folate status showed significant association with body mass index category (χ2 = 9.564, p = 0.008), indicating that overweight and obese patients were more prone to deficiency, and methotrexate (F(2.9); p = 0.06; -2LL (1381)). Haematological malignancies (F(2.8); p = 0.05; -2LL (4244)) and medium and high treatment intensity (F(2.4); p = 0.09; -2LL 4262)) were associated with higher ferritin levels over 18 months. CONCLUSIONS Paediatric cancer patients undergoing treatment exhibit high ferritin and reduced folate levels. Elevated ferritin is linked to increased toxicity and negative clinical outcomes, highlighting the importance of regular assessment and monitoring of both folate and ferritin. Implementing routine monitoring for these biomarkers could help mitigate adverse effects associated with treatment. Large-scale population-based studies and clinical trials are now warranted.
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Affiliation(s)
- Kalum Withey
- Department of Public Health and Sports Sciences, Medical School, Children's Health and Exercise Research Centre, University of Exeter, St Luke's Campus, University of Exeter, Exeter, UK
| | - Mark F H Brougham
- Department of Paediatric Haematology and Oncology, Royal Hospital for Children and Young People, Edinburgh, UK
| | - Ilenia Paciarotti
- Department of Health Sciences, Queen Margaret University, Musselburgh, Scotland
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Jane M McKenzie
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - David C Wilson
- Child Life and Health, University of Edinburgh, Edinburgh, UK
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, UK
| | - Raquel Revuelta Iniesta
- Department of Public Health and Sports Sciences, Medical School, Children's Health and Exercise Research Centre, University of Exeter, St Luke's Campus, University of Exeter, Exeter, UK
- Child Life and Health, University of Edinburgh, Edinburgh, UK
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Sansone C, Pistelli L, Brunet C. The marine xanthophyll diatoxanthin as ferroptosis inducer in MDAMB231 breast cancer cells. Sci Rep 2025; 15:8146. [PMID: 40059233 PMCID: PMC11891320 DOI: 10.1038/s41598-025-91519-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 02/20/2025] [Indexed: 05/13/2025] Open
Abstract
Marine biotopes are considered as a huge reservoir of biodiversity and chemodiversity, the latter potentially providing new treats for health prevention. Among the emphasized marine biocenosis, microorganisms such as microalgae propose suitable solutions to address eco-sustainability or biorefinery topics. The health interests of the xanthophyll diatoxanthin (Dt), a photoprotective and antioxidant pigment synthetized by diatoms, have been recently documented. This study deeply explores the capacity of Dt to intercept cancer progression and addresses the Dt -induced cell death in breast cancer. It is crucial to know which signalling pathway explaining its function is induced by the molecule in the targeted cells. This study disentangled the intracellular effects of Dt in MDAMB231 breast cancer cells. The results highlighted the inhibition of glutathione synthesis through cysteine transport blockage, that in turn, induced an iron accumulation and increase in lipid peroxidation. Those features represent the principal hallmarks of intracellular ferroptosis pathway. Ferroptosis being considered as one of the cell death most promising in fighting cancer development (e.g. in breast cancer) this study reinforces the scientific/biomedical interests on Dt and the diatoms' resource and paves the way to explore its suitability in vivo.
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Affiliation(s)
- Clementina Sansone
- Stazione Zoologica Anton Dohrn, sede Molosiglio, via F. Acton, 80133, Naples, Italy.
| | - Luigi Pistelli
- Stazione Zoologica Anton Dohrn, sede Molosiglio, via F. Acton, 80133, Naples, Italy
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy
| | - Christophe Brunet
- Stazione Zoologica Anton Dohrn, sede Molosiglio, via F. Acton, 80133, Naples, Italy
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3
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Szymulewska-Konopko K, Reszeć-Giełażyn J, Małeczek M. Ferritin as an Effective Prognostic Factor and Potential Cancer Biomarker. Curr Issues Mol Biol 2025; 47:60. [PMID: 39852175 PMCID: PMC11763953 DOI: 10.3390/cimb47010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/05/2025] [Accepted: 01/13/2025] [Indexed: 01/26/2025] Open
Abstract
Ferritin is found in all cells of the body, serving as a reservoir of iron and protecting against damage to the molecules that make up cellular structures. It has emerged as a biomarker not only for iron-related disorders but also for inflammatory diseases and conditions in which inflammation plays a key role, including cancer, neurodegeneration, and infection. Oxidative stress, which can cause cellular damage, is induced by reactive oxygen species generated during the Fenton reaction, activating signaling pathways associated with tumor growth and proliferation. This review primarily emphasizes basic studies on the identification and function of ferritin, its essential role in iron metabolism, its involvement in inflammatory diseases, and its potential as an important prognostic factor and biomarker for cancer detection.
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Affiliation(s)
| | - Joanna Reszeć-Giełażyn
- Department of Medical Pathomorphology, Medical University of Bialystok, 15-089 Białystok, Poland; (K.S.-K.); (M.M.)
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Lin J, Li Y, Lin X, Che C. Decision-level data fusion based on laser-induced breakdown and Raman spectroscopy: A study of bimodal spectroscopy for diagnosis of lung cancer at different stages. Talanta 2024; 275:126194. [PMID: 38703481 DOI: 10.1016/j.talanta.2024.126194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 04/22/2024] [Accepted: 04/30/2024] [Indexed: 05/06/2024]
Abstract
Lung cancer staging is crucial for personalized treatment and improved prognosis. We propose a novel bimodal diagnostic approach that integrates LIBS and Raman technologies into a single platform, enabling comprehensive tissue elemental and molecular analysis. This strategy identifies critical staging elements and molecular marker signatures of lung tumors. LIBS detects concentration patterns of elemental lines including Mg (I), Mg (II), Ca (I), Ca (II), Fe (I), and Cu (II). Concurrently, Raman spectroscopy identifies changes in molecular content, such as phenylalanine (1033 cm-1), tyrosine (1174 cm-1), tryptophan (1207 cm-1), amide III (1267 cm-1), and proteins (1126 cm-1 and 1447 cm-1), among others. The bimodal information is fused using a decision-level Bayesian fusion model, significantly enhancing the performance of the convolutional neural network architecture in classification algorithms, with an accuracy of 99.17 %, sensitivity of 99.17 %, and specificity of 99.88 %. This study provides a powerful new tool for the accurate staging and diagnosis of lung tumors.
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Affiliation(s)
- Jingjun Lin
- Changchun University of Technology, Changchun, Jilin, 130012, China
| | - Yao Li
- Changchun University of Technology, Changchun, Jilin, 130012, China
| | - Xiaomei Lin
- Changchun University of Technology, Changchun, Jilin, 130012, China.
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5
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Chen Z, Liang Z, Chen K, Zhang S, Huang X, Wu G, Zhu X. Serum ferritin predicted prognosis in patients with nasopharyngeal carcinoma. Sci Rep 2024; 14:4311. [PMID: 38383702 PMCID: PMC10881573 DOI: 10.1038/s41598-024-54627-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 02/14/2024] [Indexed: 02/23/2024] Open
Abstract
Elevated serum ferritin (SF) levels have been associated with poor prognosis in various cancer types, but its impact on nasopharyngeal carcinoma (NPC) remains unclear. This retrospective study analyzed clinical data from 252 non-metastatic NPC patients admitted to Hainan General Hospital between January 2014 and May 2016. SF levels were measured using the chemiluminescence method. Patients were categorized into low, medium, and high-level SF groups based on tertile median SF levels. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models. The overall survival rates of the entire patient cohort at 1, 3, 5, and 8 years were 95.2%, 85.7%, 76.2%, and 68.9% respectively. The high-level SF group (SF > 164.00 ng/mL) had significantly worse overall survival (83.1 vs 96.3 months, P = 0.023) and progression-free survival (77.8 vs 93.3 months, P = 0.019) compared to the low-level SF group. Univariate and multivariate analyses confirmed that high SF levels, along with T3/T4 staging and N3 staging, were independent risk factors for poor prognosis. In conclusion, high SF levels are associated with shorter overall survival and progression-free survival in NPC patients.
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Affiliation(s)
- Zetan Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China
| | - Zhongguo Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China
| | - Kaihua Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China
| | - Shuai Zhang
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China
| | - Xiaopeng Huang
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China
| | - Gang Wu
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China
| | - Xiaodong Zhu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China.
- Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, 530199, Guangxi, China.
- Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, 530021, Guangxi, China.
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Skakun O, Seredyuk N, Fedorov S, Verbovska O. Ferritin-haemoglobin ratio as a predictor of severity and fatal outcome in patients with Covid-19. SCRIPTA MEDICA 2023; 54:237-244. [DOI: 10.5937/scriptamed54-45157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025] Open
Abstract
Background/Aim: Although ferritin and haemoglobin were well-studied for adverse outcome prediction in COVID-19 patients, a ferritin-haemoglobin ratio (FHR) was studied poorly. The study aimed to evaluate the prognostic ability of FHR at hospital admission in hypertensive and non-hypertensive patients with COVID-19. Methods: The study included 135 patients hospitalised for COVID-19-associated pneumonia. The 78.5 % of patients were hypertensive. Results: FHR at admission was higher in patients with critical condition (39.8 [17.1-83.0]) than in patients with moderate (22.0 [12.1-32.1], p = 0.01) and severe condition (34.6 [15.1-64.5], p = 0.01). FHR was higher in patients who required supplemental oxygen (40.4 [29.4-47.8]) than in patients without the need for supplemental oxygen (22.0 [18.0-25.5]) (p = 0.001). FHR at admission was higher in non-survivors (40.1 [24.6-95.9]) than in survivors (24.5 [21.6-28.4]) (p = 0.047). FHR showed weak discriminative ability for the prediction of severe/critical conditions in hypertensive patients (AUC = 0.636, p = 0.015) and all (hypertensive and non-hypertensive patients) patients (AUC = 0.658, p = 0.001), whereas FHR had an acceptable discriminative ability in non-hypertensive patients (AUC = 0.764, p = 0.015). There was an acceptable discriminative ability of FHR for in-hospital mortality prediction in hypertensive patients (AUC = 0.717, p = 0.029). Patients with FHR > 33.98 (Youden index, 0.39) had higher odds of severe/critical clinical condition (OR: 4.57; 95 % CI: 1.87-11.18; p = 0.001). FHR of > 37.64 (Youden index, 0.55) was associated with higher in-hospital mortality among hypertensive patients (OR: 12.06; 95 % CI: 2.44-59.71; p = 0.002). There was no difference in AUC for the discriminative ability of FHR regarding severe/ critical condition (p = 0.296) and mortality (p = 0.663) in hypertensive and non-hypertensive patients. Conclusion: FHR at admission of > 33.98 is a predictor of severe/critical COVID-19 in both hypertensive and non-hypertensive patients. FHR of > 37.64 is a predictor of in-hospital mortality in hypertensive patients. There was no significant difference in the discriminative ability of FHR between hypertensive and non-hypertensive patients.
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Gao Y, Ge JT. Prognostic role of pretreatment serum ferritin concentration in lung cancer patients: A meta-analysis. World J Clin Cases 2022; 10:12230-12239. [PMID: 36483825 PMCID: PMC9724546 DOI: 10.12998/wjcc.v10.i33.12230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/19/2022] [Accepted: 10/24/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The association between pretreatment serum ferritin concentration (SFC) and long-term survival in lung cancer remains unclear now. AIM To identify the prognostic value of pretreatment SFC in lung cancer patients based on current evidence. METHODS The PubMed, EMBASE and Web of Science databases were searched from inception to May 29, 2022 for relevant studies. The primary endpoint was overall survival (OS) and the hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were combined to assess the predictive role of pretreatment SFC for long-term survival of lung cancer patients. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS Twelve retrospective studies involving 1654 patients were analyzed. The results manifested that increased pretreatment SFC was associated with worse OS (HR = 1.09, 95%CI: 1.03-1.15, P = 0.004). Subgroup analysis stratified by the country (China vs non-China) showed similar results. However, subgroup analysis stratified by tumor type revealed inconsistent results (lung cancer: HR = 1.39, P = 0.008; small cell lung cancer: HR = 1.99, P = 0.175; non-small cell lung cancer: HR = 1.03, P = 0.281). CONCLUSION Pretreatment SFC might serve as a promising prognostic indicator in lung cancer patients and elevated pretreatment SFC predicts worse prognosis. However, more high-quality studies with big sample sizes are still needed to further verify its prognostic value in lung cancer.
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Affiliation(s)
- Yang Gao
- Department of Cardiology Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223001, Jiangsu Province, China
| | - Jin-Tong Ge
- Department of Cardiology Surgery, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223001, Jiangsu Province, China
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8
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Therapeutic potential of induced iron depletion using iron chelators in Covid-19. Saudi J Biol Sci 2022; 29:1947-1956. [PMID: 34924800 PMCID: PMC8666385 DOI: 10.1016/j.sjbs.2021.11.061] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 10/24/2021] [Accepted: 11/28/2021] [Indexed: 01/09/2023] Open
Abstract
Ferritin, which includes twenty-four light and heavy chains in varying proportions in different tissues, is primarily responsible for maintaining the body's iron metabolism. Its normal value is between 10 and 200 ngmL-1 in men and between 30 and 300 ngmL-1 in women. Iron is delivered to the tissue via them, and they act as immunomodulators, signaling molecules, and inflammatory markers. When ferritin level exceeds 1000 µgL-1, the patient is categorized as having hyperferritinemia. Iron chelators such as deferiprone, deferirox, and deferoxamine are currently FDA approved to treat iron overload. The inflammation cascade and poor prognosis of COVID-19 may be attributed to high ferritin levels. Critically ill patients can benefit from deferasirox, an iron chelator administered orally at 20-40 mgkg-1 once daily, as well as intravenous deferoxamine at 1000 mg initially followed by 500 mg every 4 to 12 h. It can be combined with monoclonal antibodies, antioxidants, corticosteroids, and lactoferrin to make iron chelation therapy effective for COVID-19 victims. In this article, we analyze the antiviral and antifibrotic activity of iron chelators, thereby promoting iron depletion therapy as a potentially innovative treatment strategy for COVID-19.
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Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test. COMMUNICATIONS MEDICINE 2022; 2:29. [PMID: 35603292 PMCID: PMC9053211 DOI: 10.1038/s43856-022-00088-6] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 02/11/2022] [Indexed: 12/24/2022] Open
Abstract
Background Detecting cancer at early stages significantly increases patient survival rates. Because lethal solid tumors often produce few symptoms before progressing to advanced, metastatic disease, diagnosis frequently occurs when surgical resection is no longer curative. One promising approach to detect early-stage, curable cancers uses biomarkers present in circulating extracellular vesicles (EVs). To explore the feasibility of this approach, we developed an EV-based blood biomarker classifier from EV protein profiles to detect stages I and II pancreatic, ovarian, and bladder cancer. Methods Utilizing an alternating current electrokinetics (ACE) platform to purify EVs from plasma, we use multi-marker EV-protein measurements to develop a machine learning algorithm that can discriminate cancer cases from controls. The ACE isolation method requires small sample volumes, and the streamlined process permits integration into high-throughput workflows. Results In this case-control pilot study, comparison of 139 pathologically confirmed stage I and II cancer cases representing pancreatic, ovarian, or bladder patients against 184 control subjects yields an area under the curve (AUC) of 0.95 (95% CI: 0.92 to 0.97), with sensitivity of 71.2% (95% CI: 63.2 to 78.1) at 99.5% (97.0 to 99.9) specificity. Sensitivity is similar at both early stages [stage I: 70.5% (60.2 to 79.0) and stage II: 72.5% (59.1 to 82.9)]. Detection of stage I cancer reaches 95.5% in pancreatic, 74.4% in ovarian (73.1% in Stage IA) and 43.8% in bladder cancer. Conclusions This work demonstrates that an EV-based, multi-cancer test has potential clinical value for early cancer detection and warrants future expanded studies involving prospective cohorts with multi-year follow-up. Finding cancer early can make treatment easier and improve odds of survival. However, many tumors go unnoticed until they have grown large enough to cause symptoms. While scans can detect tumors earlier, routine full-body imaging is impractical for population screening. New cancer detection methods being explored are based on observations that tumors release tiny particles called extracellular vesicles (EVs) into the bloodstream, containing proteins from the tumor. Here, we used a method to purify EVs from patients’ blood followed by a method to detect tumor proteins in the EVs. Our method quickly and accurately detected early-stage pancreatic, ovarian, or bladder cancer. With further testing, this method may provide a useful screening tool for clinicians to detect cancers at an earlier stage. Hinestrosa et al. describe the early-stage detection of cancer using biomarkers present in circulating extracellular vesicles purified via an alternating current electrokinetics platform. They show, in a case-control study, that 95.7% of pancreatic, 75.0% of ovarian and 43.8% of bladder stage I and II cancers can be detected.
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Ren P, Wang K, Ma J, Cao X, Zhao J, Zhao C, Guo Y, Ye H. Autoantibody Against Ferritin Light Chain is a Serum Biomarker for the Detection of Liver Cirrhosis but Not Liver Cancer. J Hepatocell Carcinoma 2022; 9:221-232. [PMID: 35378780 PMCID: PMC8976487 DOI: 10.2147/jhc.s352057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/18/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Ferritin is a protein that plays an important role in iron metabolism, it consists of two subunits: heavy chain (FTH) and light chain (FTL). Elevated expression of FTL is observed in multiple malignancies. Recent studies have found that the frequency of circulating autoantibody against FTL (anti-FTL) increased significantly in hepatocellular carcinoma (HCC). The aim of this study is to verify circulating anti-FTL as a biomarker for the early detection of HCC. Patients and Methods A total of 1565 participants were enrolled and assigned to two independent validation cohorts, including 393 HCC patients, 379 liver cirrhosis (LC) patients, 400 chronic hepatitis (CH) patients, and 393 healthy subjects. The concentration of serum anti-FTL was measured by indirect Enzyme-Linked Immunosorbent Assay (ELISA). Kruskal–Wallis test was used to compare anti-FTL concentrations between HCC group and three control groups. Percentile 95 of anti-FTL absorbance value of healthy group was selected as the cut-off value to calculate the positive rate in each group. The area under receiver operating characteristic curve (AUC) was used to quantitatively describe its diagnostic value. Results The median concentration of anti-FTL in HCC patients was higher than that in CH patients and healthy subjects, but there was no difference between HCC patients and LC patients. Further analysis showed that there was no difference between early stage LC, advanced stage LC, Child-Pugh A HCC, Child-Pugh B HCC and Child-Pugh C HCC. The positive rate of anti-FTL was 12.2% (48/393) in HCC, 13.5% (51/379) in LC, 6.3% (25/400) in CH and 5.1% (20/393) in healthy subjects, respectively. The AUC of anti-FTL to distinguish LC from CH or healthy subjects were 0.654 (95% CI: 0.615–0.692) and 0.642 (95% CI: 0.602–0.681), respectively. Conclusion Anti-FTL is not a biomarker for the early diagnosis of HCC due to specificity deficiency, but may be helpful for the early detection of LC.
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Affiliation(s)
- Pengfei Ren
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, People’s Republic of China
| | - Keyan Wang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China
| | - Jie Ma
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, People’s Republic of China
| | - Xiaoqin Cao
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
| | - Jiuzhou Zhao
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, People’s Republic of China
| | - Chengzhi Zhao
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, People’s Republic of China
| | - Yongjun Guo
- Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, People’s Republic of China
- Correspondence: Yongjun Guo, Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou, 450008, People’s Republic of China, Fax +86 371 65587506 Email
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, People’s Republic of China
- Hua Ye, College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, People’s Republic of China, Fax +86 371 67781248, Email
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Carlsen L, Schorl C, Huntington K, Hernandez-Borrero L, Jhaveri A, Zhang S, Zhou L, El-Deiry WS. Pan-drug and drug-specific mechanisms of 5-FU, irinotecan (CPT-11), oxaliplatin, and cisplatin identified by comparison of transcriptomic and cytokine responses of colorectal cancer cells. Oncotarget 2021; 12:2006-2021. [PMID: 34611476 PMCID: PMC8487728 DOI: 10.18632/oncotarget.28075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 08/28/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) caused over 900,000 deaths worldwide in 2020. A majority of late-stage CRC patients are treated with 5-fluorouracil (5-FU) combined with either irinotecan (CPT-11), oxaliplatin, or both. Despite their widespread use, the mechanisms of efficacy and toxicity of these drugs remain incompletely understood. While previous work has investigated cellular responses to these agents individually, we directly compare the transcriptomic and cytokine profiles of HCT116 wild-type and p53-/- colorectal cancer cells treated with these drugs and report pan-drug, drug-specific, drug class-specific, p53-independent, and p53-dependent signatures. We observed downregulation of histone genes by 5-FU (that significantly correlates with improved survival in CRC patients) and upregulation of FOS and ATF3 by oxaliplatin (which may contribute to peripheral neuropathy). BTG2 was identified as a top gene upregulated by all four drugs, suggesting its critical role in the cellular response to chemotherapy in CRC. Soluble TRAILR2 (death receptor 5; DR5) is a decoy receptor for TRAIL, an apoptosis-inducing cytokine. TRAILR2 was down-regulated by oxaliplatin and 5-FU, was not affected by CPT-11, and was increased by cisplatin. There was an increase in IL-8 by oxaliplatin and increase in ferritin by cisplatin which may contribute to cancer cell survival. Novel drug-specific mechanisms of efficacy or toxicity identified in these signatures may be targeted with combination therapies or development of new targeted therapies. Together, the findings here contribute to our understanding of the molecular bases of efficacy and toxicity of chemotherapeutic agents often used for treatment of GI cancer such as CRC.
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Affiliation(s)
- Lindsey Carlsen
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Pathobiology Graduate Program, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Christoph Schorl
- The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Molecular Biology, Cell Biology and Biochemistry, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Genomics Core Facility, Brown University, Providence, RI 02903, USA.,Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Kelsey Huntington
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Pathobiology Graduate Program, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Liz Hernandez-Borrero
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Pathobiology Graduate Program, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Aakash Jhaveri
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Shengliang Zhang
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Lanlan Zhou
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Wafik S El-Deiry
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA.,Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Pathobiology Graduate Program, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA.,Hematology-Oncology Division, Department of Medicine, Rhode Island Hospital and Brown University, Providence, RI 02903, USA.,Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
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12
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Tirinato L, Marafioti MG, Pagliari F, Jansen J, Aversa I, Hanley R, Nisticò C, Garcia-Calderón D, Genard G, Guerreiro JF, Costanzo FS, Seco J. Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance. eLife 2021; 10:72943. [PMID: 34499029 PMCID: PMC8497056 DOI: 10.7554/elife.72943] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022] Open
Abstract
Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma, and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of lipid droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect that might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.
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Affiliation(s)
- Luca Tirinato
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Experimental and Clinical Medicine Department, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Maria Grazia Marafioti
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Experimental and Clinical Medicine Department, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesca Pagliari
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany
| | - Jeannette Jansen
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Department of Physics and Astronomy, Heidelberg University, Im Neuenheimer Feld, Heidelberg, Germany
| | - Ilenia Aversa
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Experimental and Clinical Medicine Department, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Rachel Hanley
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany
| | - Clelia Nisticò
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Experimental and Clinical Medicine Department, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Daniel Garcia-Calderón
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Department of Physics and Astronomy, Heidelberg University, Im Neuenheimer Feld, Heidelberg, Germany
| | - Geraldine Genard
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany
| | - Joana Filipa Guerreiro
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | | | - Joao Seco
- Biomedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.,Department of Physics and Astronomy, Heidelberg University, Im Neuenheimer Feld, Heidelberg, Germany
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13
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Plays M, Müller S, Rodriguez R. Chemistry and biology of ferritin. Metallomics 2021; 13:6244244. [PMID: 33881539 PMCID: PMC8083198 DOI: 10.1093/mtomcs/mfab021] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 04/09/2021] [Indexed: 02/07/2023]
Abstract
Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.
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Affiliation(s)
- Marina Plays
- Chemical Biology of Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.,Centre national de la recherche scientifique UMR 3666, Paris, France.,Institut national de la santé et de la recherche médicale U1143, Paris, France.,PSL Université Paris, Paris, France
| | - Sebastian Müller
- Chemical Biology of Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.,Centre national de la recherche scientifique UMR 3666, Paris, France.,Institut national de la santé et de la recherche médicale U1143, Paris, France.,PSL Université Paris, Paris, France
| | - Raphaël Rodriguez
- Chemical Biology of Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.,Centre national de la recherche scientifique UMR 3666, Paris, France.,Institut national de la santé et de la recherche médicale U1143, Paris, France.,PSL Université Paris, Paris, France
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14
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Hu ZW, Chen L, Ma RQ, Wei FQ, Wen YH, Zeng XL, Sun W, Wen WP. Comprehensive analysis of ferritin subunits expression and positive correlations with tumor-associated macrophages and T regulatory cells infiltration in most solid tumors. Aging (Albany NY) 2021; 13:11491-11506. [PMID: 33864445 PMCID: PMC8109065 DOI: 10.18632/aging.202841] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 03/04/2021] [Indexed: 02/07/2023]
Abstract
Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.
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Affiliation(s)
- Zhang-Wei Hu
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Lin Chen
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Ren-Qiang Ma
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Fan-Qin Wei
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Yi-Hui Wen
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Xue-Lan Zeng
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Wei Sun
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China
| | - Wei-Ping Wen
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Otorhinolaryngology Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong, P.R. China.,Department of Otolaryngology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong, P.R. China
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15
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Steele T, Bonwick H, Nwosu AC, Chapman L. Investigation and management of iron deficiency anaemia in a specialist palliative care setting and the role of intravenous iron: a descriptive analysis of hospice data. AMRC OPEN RESEARCH 2021; 3:6. [PMID: 38708071 PMCID: PMC11064982 DOI: 10.12688/amrcopenres.12963.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 05/07/2024]
Abstract
Background Anaemia is common in hospice populations and associated with significant symptom burden. Guidelines recommend investigating for and treating iron deficiency (ID), but there is little evidence of this practice in palliative care populations. This report describes the results of investigations for and subsequent management of ID in a UK hospice. Methods This is a descriptive study of routine clinical data. Laboratory and clinical records were reviewed retrospectively for 12 months following the implementation, in August 2018, of routine investigation for ID amongst patients with clinically relevant anaemia in whom treatment would be considered. Absolute (AID) and functional iron deficiency (FID) were diagnosed using established definitions and treatments recorded. Results Iron status was evaluated in 112 cases, representing 25/110 (22.7%) of those with mild, 46/76 (60.5%) moderate and 41/54 (75.9%) severe anaemia. Twenty-eight (25%) were defined as having AID, 48 (42.8%) FID and 36 (32%) no ID. There was a significant difference between groups in symptoms triggering haemoglobin check and diagnosis, with a higher proportion of patients with classic symptoms of anaemia and gastrointestinal malignancy in those with AID. Intravenous iron was given on 12 occasions in the hospice with no major adverse events. Subjective symptom benefit in 7 cases and a statistically significant increase in overall mean haemoglobin were observed. Conclusions This report describes the outcome of investigations for iron deficiency in patients with clinically significant anaemia in a UK hospice. Results indicate iron deficiency is common and can be safely treated with intravenous iron replacement, within current guidelines, in a hospice setting. Further research should define the optimum use of this approach in palliative care patients.
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Affiliation(s)
- Thomas Steele
- Marie Curie Hospice, Liverpool, Merseyside, L25 8QA, UK
| | - Helen Bonwick
- Marie Curie Hospice, Liverpool, Merseyside, L25 8QA, UK
| | - Amara Callistus Nwosu
- Marie Curie Hospice, Liverpool, Merseyside, L25 8QA, UK
- International Observatory on End of Life Care, Lancaster University, Lancaster, Lancashire, LA1 4YG, UK
- Liverpool University Hospitals NHS Trust, Liverpool, Merseyside, L7 8XP, UK
| | - Laura Chapman
- Marie Curie Hospice, Liverpool, Merseyside, L25 8QA, UK
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16
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Kaviarasi R, Gandhi Raj R. Prediction System for the Lung Cancer Patients and Classification Accuracy Enhancement Using Ensemble Method. JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS 2021. [DOI: 10.1166/jmihi.2021.3530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Lung cancer is the biggest challenge in the research world. Blood samples for lung cancer patients are significant for the prediction method in the research environment. Accurate prediction is essential to increase the survival period and may help to take proper medication. The feature
selection is an essential part of this prediction system. In this method, the essential features are analyzed from lung cancer patient’s blood. Biomarkers can be identified from blood and other tests. Biomarkers are used in many scientific fields. The Serum CKAP4 levels were analyzed
from lung cancer patient’s blood at the TNM stages. White blood counts and Hemoglobin are viewed as an analysis of immunity, and CKAP4 is located at an immunity level that has been recognized in the body fluid of patients with lung cancer. The system is analyzed immunity from collected
real health information by a proposed Gaussian Kb Ensemble Weighting Classifier method. The novel attributes are composed of a cancer research center and cancer sanatoriums. The measurement of weighting value {low = 0, high = 1} of blood in Serum CKAP4, Hemoglobin, and the
WBC are classified by immunity range. High immunity people’s survival rate is high at TNM stage 1. If not, high immunity was survival rate is low at TNM stage 1. Lung cancer patient’s survivability classification was performed by various supervised machine learning models such
as Ada boost, neural networks, and SVM model. The Gaussian Kb Ensemble Weighting Classifier method helped to improve the classification accuracy by feature selection and the algorithm was implemented in the MATLAB environment. Kaplan–Meier curve method used to analyzes
results. The classified labels are compared with existing results. The area proved the Gaussian Kb Ensemble weighting classifier algorithm under the Curve through the ROC method.
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Affiliation(s)
- R. Kaviarasi
- Department of Computer Applications, University College of Engineering (BIT Campus), Anna University, Tiruchirappalli 620024, TamilNadu, India
| | - R. Gandhi Raj
- Department of Electricals and Electronics Engineering, University College of Engineering (BIT Campus), Anna University, Tiruchirappalli 620024, TamilNadu, India
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17
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Lu C, Zhao H, Luo C, Lei T, Zhang M. Knockdown of ferritin heavy chain (FTH) inhibits the migration of prostate cancer through reducing S100A4, S100A2, and S100P expression. Transl Cancer Res 2020; 9:5418-5429. [PMID: 35117907 PMCID: PMC8797967 DOI: 10.21037/tcr-19-2852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 07/08/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND Ferritin plays a key role in the development of prostate cancer (PCa). Our earlier studies showed that the knockdown of ferritin heavy chain (FTH) suppressed the migration and invasion of the prostate cancer cell line (PC3). However, the mechanisms behind FTH in the cell migration regulation of PCa have not been thoroughly investigated. METHODS Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics was used to analyze the protein expression in PC3 cells with FTH knockdown by small interfering RNAs and negative control cells. We subsequently ranked the differentially expressed proteins according to the change in expression. We further performed Gene Ontology (GO) analysis for the changing-expression protein. Finally, Western blot analysis was performed to determine the expression of the target protein. RESULTS Compared with the negative group, 420 proteins were downregulated, including proteins S100A4, S100P, and S100A2, while the expression of 442 protein was elevated in FTH-silencing PC3 cells (P<0.05, fold change >1.2). The mass spectrometry results showing decreased expression of protein S100A4, S100P, and S100A2 in the cells were further validated by Western blot (P<0.05). Levels of protein S100A4, S100A2, and S100P were reduced in FTH-silencing PC3 cells (P<0.05, fold change >1.6). CONCLUSIONS The downregulation of FTH expression reduced the level of protein S100A4, S100A2, and S100P, which all play a key role in the migration and invasion of tumor cells. Therefore, it is reasonable to assume that there are correlations between the expression of the S100A4, S100A2, and S100P genes with FTH. Based on this research, FTH may be a new biomarker for the diagnosis of PCa.
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Affiliation(s)
- Cuixiu Lu
- Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China
| | - Huijun Zhao
- Clinical Laboratory Medicine, Capital Medical University, Beijing, China
| | - Chenshuo Luo
- Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China
| | - Ting Lei
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Man Zhang
- Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China.,Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
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18
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Han J, Xu Y, Zhou Y, Yang A, Cui J, Chen P, Zhao H, Zhou X, Shen C, Yu J, Lu H. The effect of TKI therapy and chemotherapy treatment delivery sequence on total progression-free survival in patients with advanced EGFR-mutated NSCLC. Oncol Lett 2020; 20:391-400. [PMID: 32565965 DOI: 10.3892/ol.2020.11535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 01/21/2020] [Indexed: 12/25/2022] Open
Abstract
The present study aimed to evaluate the total progression-free survival (PFS) time of the 1st-line chemotherapy (CHT)/2nd-line tyrosine kinase inhibitor (TKI) and 1st-line TKI/2nd-line CHT therapeutic regimens. Data from patients with non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations, who had received both TKI and platinum CHT were retrieved from the Shandong Cancer Hospital (Jinan, China) database. A total of 89 patients were included, 50 of whom were treated with the 1st-line CHT/2nd-line TKI regimen and the remaining 39 patients underwent a 1st-line TKI/2nd-line CHT regimen. The differences in total PFS time between the two regimens were analyzed. The median total PFS time was 14.28 months with the 1st-line CHT/2nd-line TKI regimen and 17.77 months with the 1st-line TKI/2nd-line CHT regimen (adjusted hazard ratio, 0.96; 95% confidence interval (CI), 0.56-1.66; P=0.886). A significant difference in PFS time was revealed between the two strategies when comparing only the 1st-line or 2nd-line treatments (all P<0.001). The objective response rate (RR) was 52.0% for those treated with 1st-line CHT/2nd-line TKI and 38.5% for the reverse regimen. After adjusting for associated factors, the odds ratio for the RR was 2.77 (95% CI: 0.77-9.90; P=0.117). The current results revealed that there was no significant difference between the total PFS time of patients with NSCLC undergoing the 1st-line CHT/2nd-line TKI regimen compared with patients with NSCLC undergoing the 1st-line TKI/2nd-line CHT regimen.
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Affiliation(s)
- Jie Han
- Department of Radiation Oncology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Yan Xu
- Department of Oncology, Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, Shandong 276800, P.R. China
| | - Yumei Zhou
- Department of Oncology, The People's Hospital of Rizhao City, Jinan, Shandong 250117, P.R. China
| | - Aiju Yang
- Department of Nursing, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Jinan, Shandong 250117, P.R. China
| | - Jianfeng Cui
- Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
| | - Pengxiang Chen
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
| | - Hongyu Zhao
- Department of Radiation Oncology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Xingqin Zhou
- Department of Radiation Oncology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Chaoyan Shen
- Department of Radiation Oncology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Jinan, Shandong 250117, P.R. China
| | - Heng Lu
- Department of Pathology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
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19
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Chen MY, Juengpanich S, Hu JH, Topatana W, Cao JS, Tong CH, Lin J, Cai XJ. Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma. World J Gastroenterol 2020; 26:1042-1055. [PMID: 32205995 PMCID: PMC7081004 DOI: 10.3748/wjg.v26.i10.1042] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 12/20/2019] [Accepted: 02/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.
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Affiliation(s)
- Ming-Yu Chen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
- School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Engineering Research Center of Cognitive Healthcare of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
| | - Sarun Juengpanich
- School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Jia-Hao Hu
- School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Win Topatana
- School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Jia-Sheng Cao
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Chen-Hao Tong
- Department of General Surgery, Shaoxing People’s Hospital, Zhejiang University, Shaoxing 312000, Zhejiang Province, China
| | - Jian Lin
- Department of General Surgery, Longyou People’s Hospital, Quzhou 314400, Zhejiang Province, China
| | - Xiu-Jun Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
- School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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