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Sharafi Monfared M, Nazmi S, Parhizkar F, Jafari D. Soluble B7 and TNF family in colorectal cancer: Serum level, prognostic and treatment value. Hum Immunol 2025; 86:111232. [PMID: 39793378 DOI: 10.1016/j.humimm.2025.111232] [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: 10/24/2024] [Revised: 12/25/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025]
Abstract
Soluble immune checkpoints (sIC) are crucial factors in the immune system. They regulate immune responses by transforming intercellular signals via binding to their membrane-bound receptor or ligand. Moreover, soluble ICs are vital in immune regulation, cancer development, and prognosis. They can be identified and measured in various tumor microenvironments. Recently, sICs have become increasingly important in clinically assessing malignancies like colorectal cancer (CRC) patients. This review explores the evolving role of the soluble B7 family and soluble tumor necrosis factor (TNF) superfamily members in predicting disease progression, treatment response, and overall patient outcomes in CRC. We comprehensively analyze the diagnostic and prognostic potential of soluble immune checkpoints in CRC. Understanding the role of these soluble immune checkpoints in CRC management and their potential as targets for precision medicine approaches can be critical for improving outcomes for patients with colorectal cancer.
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Affiliation(s)
- Mohanna Sharafi Monfared
- Student's Research Committee, Zanjan University of Medical Sciences, Zanjan, Iran; School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sina Nazmi
- Student's Research Committee, Zanjan University of Medical Sciences, Zanjan, Iran; School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Forough Parhizkar
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Davood Jafari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
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Ranjitham PS, Kuzhali S, Sumathy MP, Gnandeepam S. Evaluation of Platelet Parameters in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma in a Background of Oral Submucous Fibrosis. Indian J Dent Res 2023; 34:417-421. [PMID: 38739824 DOI: 10.4103/ijdr.ijdr_538_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 10/23/2023] [Indexed: 05/16/2024] Open
Abstract
CONTEXT The role of platelet parameters as markers of inflammation in various diseases is now in limelight. The interaction between cancer cells and platelets is a well-established phenomenon. Oral submucous fibrosis (OSMF) is a premalignant disorder with a malignant transformation rate of 2-8%. This study aimed to evaluate platelet parameters in OSMF and oral squamous cell carcinoma (OSCC) in the background of OSMF. This cross-sectional study was performed using secondary data retrieved between January 2019 and December 2019 in the Department of Oral Pathology and the Hematology Laboratory. METHODS AND MATERIALS The data retrieved included 44 histopathologically proven OSCC in a background of OSMF (group III) and 36 OSMF (group II). The haematological parameters of these selected cases were retrieved from the Sysmex XN-1000 automated hematology analyser database. A control group (group I) comprises 50 subjects with normal (negative/unflagged) haematological parameters. All data were statistically analysed using SPSS 20.0. The significance level of tests was set at 5%. RESULTS The mean platelet volume (MPV) (9.60 [±0.95] P < 0.001), platelet distribution width (PDW) (10.45 [±1.9], P < 0.001), platelet large cell ratio (PLCR) (21.70 [±7.98], P < 0.001), and the ratio of mean platelet volume to total platelet count (MPV/PLT) (0.03 [0.01], P < 0.001) were lower in group III when compared to the other two groups. CONCLUSIONS Platelet parameters may be used as indices in the OSCC in the background of OSMF. However, large-scale prospective studies are necessary to evaluate the utility of these parameters during the malignant transformation of OSMF, thereby encouraging prompt treatment to prevent morbidity and mortality.
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Affiliation(s)
- Packiaraj Selvajothi Ranjitham
- Department of Oral Pathology, Tamil Nadu Government Dental College and Hospital, Affiliated to Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
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Feka J, Jomrich G, Winkler D, Ilhan-Mutlu A, Kristo I, Paireder M, Rieder E, Bologheanu M, Asari R, Schoppmann SF. Platelets as a prognostic factor for patients with adenocarcinoma of the gastroesophageal junction. Langenbecks Arch Surg 2023; 408:351. [PMID: 37673810 PMCID: PMC10482770 DOI: 10.1007/s00423-023-03093-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 09/01/2023] [Indexed: 09/08/2023]
Abstract
OBJECTIVE The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with resectable adenocarcinomas of the gastroesophageal junction. BACKGROUND Platelet activation, quantified by PLT and elevated MPV, plays an essential part in the biological process of carcinogenesis and metastasis. An increased preoperative COP-MPV is associated with poor survival in various tumor entities. METHODS Data of 265 patients undergoing surgical resection for adenocarcinoma of the gastroesophageal junction were abstracted. COP-MPV score was defined for each patient. Utilizing univariate and multivariate Cox proportional hazard analyses, survival was determined. RESULTS In univariate analysis, elevated PLT (HR 3.58, 95% CI 2.61-4.80, p<0.001) and increased COP-MPV (HR 0.27, 95% CI 0.17-0.42, p<0.001 and HR 0.42, 95% CI 0.29-0.60, p<0.001) significantly correlated with shorter patients' overall and disease-free survival, for all 256 patients, as well as in the subgroups of neoadjuvantly treated (p<0.001) and primarily resected patients (p<0.001). COP-MPV remained a significant prognostic factor in multivariate analysis for OS. However, PLT alone showed significant diminished OS and DFS in all subgroups (p<0.001) in univariate and multivariate analysis. CONCLUSION PLT is a potent independent prognostic biomarker for survival in a large prospective cohort of patients with resectable adenocarcinoma of the gastroesophageal junction. Additionally, we confirm that the COP-MPV score is significantly associated with worse outcome in these patients, but has no benefit in comparison to PLT.
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Affiliation(s)
- Joy Feka
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Gerd Jomrich
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Daniel Winkler
- Department of Statistics and Operations Research, University of Vienna, Oskar Morgenstern Platz 1, 1090, Vienna, Austria
| | - Ayseguel Ilhan-Mutlu
- Department of Medicine 1, Comprehensive Cancer Center (CCC), Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Ivan Kristo
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Matthias Paireder
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Erwin Rieder
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Milena Bologheanu
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Reza Asari
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Sebastian F Schoppmann
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
- Upper-GI Unit, Department of Surgery, Division of General Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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Hu JL, Zhang WJ. The role and pharmacological properties of P2Y12 receptor in cancer and cancer pain. Biomed Pharmacother 2023; 157:113927. [PMID: 36462316 DOI: 10.1016/j.biopha.2022.113927] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/22/2022] [Accepted: 10/24/2022] [Indexed: 12/05/2022] Open
Abstract
The G protein-coupled P2Y12 receptor (P2Y12R) was cloned in platelets and found to play a key role in maintaining platelet function in hemostasis and thrombosis, and these effects could be mediated by the P2Y12R. However, it has recently been found that P2Y12R-mediated the progression of tumor through interactions between platelets and tumor and stromal cells, as well as through products secreted by platelets. During tumor progression, tumor cells or other cells in the tumor microenvironment (such as immune cells) can secrete large amounts of ATP into the extracellular matrix, and extracellular ATP can be hydrolyzed into ADP. ADP is a P2Y12R activator and plays an important regulatory role in the proliferation and metastasis of tumor cells. P2Y12R is involved in platelet-cancer cell crosstalk and become a potential target for anticancer therapy. Moreover, tumor progression can induce pain, which seriously affects the quality of life of patients. P2Y12R is expressed in microglia and mediates the activities of microglial and participates in the occurrence of cancer pain. Conversely, inhibiting P2Y12R activation and down-regulating its expression has the effect of inhibiting tumor progression and pain. Therefore, P2Y12R can be a common therapeutic target for both. In this article, we explored the potential link between P2Y12R and cancer, discussed the intrinsic link of P2Y12R in cancer pain and the pharmacological properties of P2Y12R antagonists in the treatment of both.
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Affiliation(s)
- Jia-Ling Hu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China
| | - Wen-Jun Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China.
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Chi XJ, Song YB, Liu DH, Wei LQ, An X, Feng ZZ, Lan XH, Lan D, Huang C. Significance of platelet adhesion-related genes in colon cancer based on non-negative matrix factorization-based clustering algorithm. Digit Health 2023; 9:20552076231203902. [PMID: 37766908 PMCID: PMC10521306 DOI: 10.1177/20552076231203902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Background Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848-0.910). Conclusion The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.
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Affiliation(s)
- Xiao-jv Chi
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, China
| | - Yi-bei Song
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, China
| | - Deng-he Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, China
| | - Li-qiang Wei
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, China
| | - Xin An
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zi-zhen Feng
- The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiao-hua Lan
- The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Dong Lan
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chao Huang
- School of Information and Management, Guangxi Medical University, Nanning, China
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Ma X, Ou K, Liu X, Yang L. Application progress of liquid biopsy in gastric cancer. Front Oncol 2022; 12:969866. [PMID: 36185234 PMCID: PMC9521037 DOI: 10.3389/fonc.2022.969866] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors globally. Guiding the individualized treatment of GC is the focus of research. Obtaining representative biological samples to study the biological characteristics of GC is the focus of diagnosis and treatment of GC. Liquid biopsy technology can use high-throughput sequencing technology to detect biological genetic information in blood. Compared with traditional tissue biopsy, liquid biopsy can determine the dynamic changes of tumor. As a noninvasive auxiliary diagnostic method, liquid biopsy can provide diagnostic and prognostic information concerning the progression of the disease. Liquid biopsy includes circulating tumor cells, circulating tumor DNA, circulating tumor RNA, tumor educated platelets, exosomes, and cytokines. This article describes the classification of liquid biopsy and its application value in the occurrence, development, and therapeutic efficacy of GC.
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Li W, Syed F, Yu R, Yang J, Xia Y, Relich RF, Russell PM, Zhang S, Khalili M, Huang L, Kacena MA, Zheng X, Yu Q. Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection. Front Immunol 2022; 13:833310. [PMID: 35281051 PMCID: PMC8904355 DOI: 10.3389/fimmu.2022.833310] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 01/28/2022] [Indexed: 01/08/2023] Open
Abstract
Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.
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Affiliation(s)
- Wei Li
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Fahim Syed
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Richard Yu
- Department of Internal Medicine, School of Medicine, University of Nevada, Reno, NV, United States
| | - Jing Yang
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Ying Xia
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
- School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China
| | - Ryan F. Relich
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Patrick M. Russell
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Shanxiang Zhang
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Mandana Khalili
- Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Laurence Huang
- Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Melissa A. Kacena
- Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Xiaoqun Zheng
- School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China
- Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qigui Yu
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
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Yuan B, Liu D, Zhu Z, Hao Y, He K, Deng S. Effect of Thoracic Paravertebral Nerve Block on Blood Coagulation in Patients After Thoracoscopic Lobectomy: A Prospective Randomized Controlled Clinical Trial. J Pain Res 2022; 15:633-641. [PMID: 35250307 PMCID: PMC8896523 DOI: 10.2147/jpr.s355227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 02/24/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Baohong Yuan
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Danyan Liu
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
- Correspondence: Danyan Liu, Tel/Fax +86 23 8901 1069, Email
| | - Zunyan Zhu
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Yonggang Hao
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Kaihua He
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Shiyun Deng
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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Li C, Zhang H, Li S, Zhang D, Li J, Dionigi G, Liang N, Sun H. Prognostic Impact of Inflammatory Markers PLR, LMR, PDW, MPV in Medullary Thyroid Carcinoma. Front Endocrinol (Lausanne) 2022; 13:861869. [PMID: 35350101 PMCID: PMC8957807 DOI: 10.3389/fendo.2022.861869] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 02/11/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), mean platelet volume (MPV), and platelet distribution width (PDW) have been used as prognostic biomarkers in various cancers. We aim to investigate the relationship between the above inflammatory indices, clinicopathological features, and postoperative calcitonin (Ctn) progression in medullary thyroid carcinoma (MTC). METHODS Sixty-eight patients diagnosed with MTC who underwent surgery at our institution between 2009 and 2020 were retrospectively evaluated. Areas under the receiver operating characteristic curves (ROC) and logistic regression were applied to explore the potential risk factors. RESULTS PDW was predictive of lymph node metastasis (LN) (AUC=0.645, P=0.044), PLR, PDW, and MPV were predictive of capsule invasion (AUC=0.771, P=0.045; AUC=0.857, P=0.008; and AUC =0.914, P=0.002, respectively), and MPV and LMR were predictive of postoperative Ctn progression (AUC=0.728, P=0.003; AUC=0.657, P=0.040). Multivariate analysis revealed that PDW ≤ 16.4 [(OR=7.8, 95% CI: 1.532-39.720, P=0.013)] and largest tumor size ≥1 cm (OR=4.833, 95% CI: 1.514-15.427, P=0.008) were potential independent risk factors for lateral LN metastasis. We also found that, MPV ≤ 8.2(OR=13.999, 95% CI: 2.842-68.965, P=0.001), LMR ≤ 4.7 (OR=4.790, 95% CI: 1.034-22.187, P=0.045), and N1 (OR=45.890, 95%CI:3.879-542.936, P=0.002) were potential independent risk factors for postoperative Ctn progression. In addition, compared with the single indicator, the appropriate combination of MPV and LMR could improve the specificity and sensitivity of predicting postoperative Ctn progression. CONCLUSIONS PLR, LMR, PDW, and MPV were associated with clinicopathological features and postoperative Ctn progression in MTC, suggesting that those inflammatory indices might be potential biomarkers of MTC.
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Affiliation(s)
- Canxiao Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Han Zhang
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Shijie Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Daqi Zhang
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Jingting Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Gianlorenzo Dionigi
- Division of General and Endocrine Surgery, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Nan Liang
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
- *Correspondence: Hui Sun, ; Nan Liang,
| | - Hui Sun
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
- *Correspondence: Hui Sun, ; Nan Liang,
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THE EFFECTS OF THYROID-STIMULATING HORMONE, FREE THYROXINE LEVELS, AND THYROID ANTIBODIES ON MEAN PLATELET VOLUME: ORIGINAL RESEARCH. JOURNAL OF CONTEMPORARY MEDICINE 2022. [DOI: 10.16899/jcm.932053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Li C, Li J, Li S, Zhao Y, Liu G, Du R, Dionigi G, Liang N, Sun H. Prognostic significance of inflammatory markers LMR, PLR, MPV, FIB in intermediate-and high-risk papillary thyroid carcinoma. Front Endocrinol (Lausanne) 2022; 13:984157. [PMID: 36060974 PMCID: PMC9434795 DOI: 10.3389/fendo.2022.984157] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 07/27/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and fibrinogen (FIB) have been identified as predictive biomarkers in several malignancies. The aim of this study was to explore the association between inflammatory index with clinicopathologic features as well as recurrence risk in intermediate-to high-risk papillary thyroid carcinoma (PTC). METHODS Retrospective evaluation of 212 patients diagnosed with intermediate-to high-risk PTC who underwent surgery at China-Japan Union Hospital between 2015 and 2016. Logistic regression and receiver operating curves (ROC) were used to explore possible risk factors. RESULTS LMR was predictive of capsular invasion (AUC=0.595, P=0.017), FIB was predictive of lymph node metastasis (LN) (AUC=0.714, P=0.002), MPV was predictive of largest LN size ≥1cm (AUC=0.639, P=0.002), PLR and MPV were predictive of recurrence (AUC=0.616, P=0.032; AUC=0.626, P=0.020). In addition, FIB ≤ 2.6 (OR=6.440, 95%CI:1.777-23.336, P=0.005) and capsular invasion (OR=3.773, 95%CI:1.171-12.159, P=0.026) were identified as independent risk factors for lymph node metastasis by multivariate analysis. In addition, LN metastasis (P=0.048), largest LN size ≥ 1 cm (P=0.032), MPV > 9.4 (P=0.046), and PLR ≤ 128.1 (P=0.032) were significantly related with recurrence. Further multivariate regression analysis revealed that PLR ≤ 128.1 was a potentially independent risk factor for recurrence. Specifically, the risk of recurrence was 2.951 times higher in patients with a PLR ≤ 128.1 compared with patients with a PLR > 128.1 (OR=2.951, 95% CI:1.238-7.037, P=0.015). CONCLUSION In intermediate-to high-risk PTC, LMR, PLR, MPV, and FIB could predict clinicopathologic features and recurrence, with lower PLR being the potential risk factors for recurrence.
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Affiliation(s)
- Canxiao Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Jingting Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Shijie Li
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Yishen Zhao
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Guandong Liu
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Rui Du
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
| | - Gianlorenzo Dionigi
- Division of Surgery, Istituto Auxologico Italiano IRCCS (Istituto di Ricovero e Cura a Carattere Scientifco), Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Nan Liang
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
- *Correspondence: Hui Sun, ; Nan Liang, liangnan2006@ jlu.edu.cn
| | - Hui Sun
- Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid Carcinoma, Changchun, China
- *Correspondence: Hui Sun, ; Nan Liang, liangnan2006@ jlu.edu.cn
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Halawi M. Prognostic Value of Evaluating Platelet Role, Count and Indices in Laboratory Diagnosis of Different Types of Solid Malignancies. Pak J Biol Sci 2022; 25:100-105. [PMID: 35233997 DOI: 10.3923/pjbs.2022.100.105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Platelets are associated with the processes that aid in tumour growth and progression. Platelet Count (PLT) and platelet indices like Mean Platelet Volume (MPV), Platelet Large Cell Ratio (P-LCR), Plateletcrit (PCT) and Platelet Distribution Width (PDW) are markers that are linked with platelet activities in cancer. This review involves the evaluation of PLT, MPV and PCT in different cancers. Platelets actions should be always monitored during several diseases, as their potential exceeds the classical function in preventing bleeding. Vast roles of platelets were discovered in several biological functions. Therefore, studying their indices can be effective in the diagnosis of several disorders including cancer.
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13
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Preoperative Thrombocytosis is Not Associated with Overall Survival in 309 Glioblastoma Patients. J Neurol Surg A Cent Eur Neurosurg 2021; 83:548-554. [PMID: 34897615 DOI: 10.1055/s-0041-1739501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM). METHODS A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis. The association of potential risk factors with overall survival was assessed using the Kaplan-Meier survival analysis and Cox regression. RESULTS The present study includes 309 patients first diagnosed with primary GBM. Our analyses validate well-known risk factors of a decreased overall survival such as higher patient age, a larger preoperative tumor volume, Karnofsky performance status, extent of resection, tumor localization, and adjuvant treatment. However, no correlation was observed between a preoperative thrombocytosis, the mean platelet volume, leucocyte count, activated partial thromboplastin time (apTT), fibrinogen level, and acetylsalicylic acid 100 co-medication. Patients with preoperative hemoglobin below 7.5 mmol/L had decreased overall survival. CONCLUSION The present study, enrolling the largest numbers of patients assessing this topic to date, did not find any association between a preoperative thrombocytosis and overall survival in 309 patients with GBM.
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Gao J, Wang Y, Lyu B, Chen J, Chen G. Component Identification of Phenolic Acids in Cell Suspension Cultures of Saussureainvolucrata and Its Mechanism of Anti-Hepatoma Revealed by TMT Quantitative Proteomics. Foods 2021; 10:foods10102466. [PMID: 34681515 PMCID: PMC8535732 DOI: 10.3390/foods10102466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 12/13/2022] Open
Abstract
Saussurea involucrata (S. involucrata) had been reported to have anti-hepatoma function. However, the mechanism is complex and unclear. To evaluate the anti-hepatoma mechanism of S. involucrata comprehensively and make a theoretical basis for the mechanical verification of later research, we carried out this work. In this study, the total phenolic acids from S. involucrata determined by a cell suspension culture (ESPI) was mainly composed of 4,5-dicaffeoylquinic acid, according to the LC-MS analysis. BALB/c nude female mice were injected with HepG2 cells to establish an animal model of liver tumor before being divided into a control group, a low-dose group, a middle-dose group, a high-dose group, and a DDP group. Subsequently, EPSI was used as the intervention drug for mice. Biochemical indicators and differences in protein expression determined by TMT quantitative proteomics were used to resolve the mechanism after the low- (100 mg/kg), middle- (200 mg/kg), and high-dose (400 mg/kg) interventions for 24 days. The results showed that EPSI can not only limit the growth of HepG2 cells in vitro, but also can inhibit liver tumors significantly with no toxicity at high doses in vivo. Proteomics analysis revealed that the upregulated differentially expressed proteins (DE proteins) in the high-dose group were over three times that in the control group. ESPI affected the pathways significantly associated with the protein metabolic process, metabolic process, catalytic activity, hydrolase activity, proteolysis, endopeptidase activity, serine-type endopeptidase activity, etc. The treatment group showed significant differences in the pathways associated with the renin-angiotensin system, hematopoietic cell lineage, etc. In conclusion, ESPI has a significant anti-hepatoma effect and the potential mechanism was revealed.
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Affiliation(s)
- Junpeng Gao
- College of Life Science, Jilin Agricultural University, Changchun 130118, China;
| | - Yi Wang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China; (Y.W.); (B.L.); (J.C.)
| | - Bo Lyu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China; (Y.W.); (B.L.); (J.C.)
- College of Food Science, Northeast Agricultural University, Harbin 150030, China
| | - Jian Chen
- College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China; (Y.W.); (B.L.); (J.C.)
| | - Guang Chen
- College of Life Science, Jilin Agricultural University, Changchun 130118, China;
- Correspondence:
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15
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Ng SSW, Zhang H, Wang L, Citrin D, Dawson LA. Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity. NPJ Precis Oncol 2020; 4:17. [PMID: 32695883 PMCID: PMC7360781 DOI: 10.1038/s41698-020-0124-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 05/15/2020] [Indexed: 02/08/2023] Open
Abstract
Plasma levels of soluble factors early during hepatocellular carcinoma (HCC) stereotactic body radiotherapy (SBRT) were evaluated in relation to radiation liver injury, tumor response, and risk of early death. No significant differences were found in baseline plasma levels of AFP, CXCL1, and HGF amongst HCC patients with different Child Pugh scores. Higher levels of sTNFRII (P < 0.001), and lower levels of sCD40L (P < 0.001) and CXCL1 (P = 0.01) following one to two fractions of SBRT were noted in patients who developed liver toxicity vs. those who did not. High circulating levels of AFP (HR 2.16, P = 0.04), sTNFRII (HR 2.27, P = 0.01), and sIL-6R (HR 1.99, P = 0.03) early during SBRT were associated with increased risk of death 3 months post treatment. Plasma levels of the studied factors early during SBRT were not associated with tumor response. A pro-inflammatory systemic environment is associated with development of liver toxicity and increased risk of early death following SBRT.
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Affiliation(s)
- Sylvia S. W. Ng
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON Canada
| | - Hong Zhang
- Radiation Oncology Branch, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD USA
| | - Lisa Wang
- Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON Canada
| | - Deborah Citrin
- Radiation Oncology Branch, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD USA
| | - Laura A. Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON Canada
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16
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Wang JJ, Wang YL, Ge XX, Xu MD, Chen K, Wu MY, Gong FR, Tao M, Wang WJ, Shou LM, Li W. Prognostic Values of Platelet-Associated Indicators in Resectable Lung Cancers. Technol Cancer Res Treat 2019; 18:1533033819837261. [PMID: 30871415 PMCID: PMC6421614 DOI: 10.1177/1533033819837261] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background: Lung cancer is the leading cause of cancer death. Platelet-related indictors, including platelet count, plateletcrit, mean platelet volume, and platelet distribution width, not only associate with morphology and functions of platelet but also correlate with tumor development and metastasis. In the present study, we investigated the values of platelet-related indictors in the prognosis evaluation of resectable lung cancers. Methods: In total, 101 patients with resectable lung cancer were recruited in this study. Patients were divided into 2 groups according to the median pretreatment values. To evaluate the individual value changes after treatment, we introduced the concept of post-/pretreatment ratio (≤1 indicated value was not increased after treatment, while >1 suggested increased value). Results: The high pretreatment platelet count level was correlated with larger tumor size. High pretreatment plateletcrit level was associated with more lymph nodes metastasis. Patients with high pretreatment plateletcrit level had worse overall survival, whereas pretreatment platelet count, mean platelet volume, and platelet distribution width levels were not correlated with outcomes. Surgery had no impact on the values of platelet count, plateletcrit, mean platelet volume, or platelet distribution width. Adjuvant chemotherapy significantly decreased the values of platelet count and plateletcrit, whereas it had no effect on the values of mean platelet volume or platelet distribution width. Whole course of treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of platelet count and platelet distribution width, whereas it had no effect on the values of plateletcrit or mean platelet volume. Post-/pretreatment platelet count, plateletcrit, mean platelet volume, and platelet distribution width ratios were not correlated with outcomes. Univariate analyses demonstrated that American Joint Committee on Cancer stage and pretreatment plateletcrit level were significant risk factors for prognosis. Cox regression analysis revealed that no factor independently associated with worse survival. Conclusion: Pretreatment plateletcrit level could be a potential prognostic factor in resectable lung cancers.
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Affiliation(s)
- Jing-Jing Wang
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.,2 Department of Gastroenterology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, China
| | - Yin-Ling Wang
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xin-Xin Ge
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Meng-Dan Xu
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Kai Chen
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Meng-Yao Wu
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fei-Ran Gong
- 3 Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Min Tao
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.,4 PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, China
| | - Wen-Jie Wang
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.,5 Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China
| | - Liu-Mei Shou
- 6 Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Wei Li
- 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.,4 PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, China.,7 Comprehensive Cancer Center, Suzhou Xiangcheng People's Hospital, Suzhou, China
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17
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Sakin A, Secmeler S, Arici S, Geredeli C, Yasar N, Demir C, Aksaray F, Cihan S. Prognostic Significance of Mean Platelet Volume on Local Advanced Non-Small Cell Lung Cancer Managed with Chemoradiotherapy. Sci Rep 2019; 9:3959. [PMID: 30850724 PMCID: PMC6408473 DOI: 10.1038/s41598-019-40589-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 02/19/2019] [Indexed: 11/10/2022] Open
Abstract
Mean platelet volume (MPV), the most commonly used measure of platelet size, and is altered in patients with malignancies. The aim of this study was to investigate the effect of MPV on overall survival (OS) of patients with locally advanced (Stage IIIA/B) inoperable non-small cell lung cancer (NSCLC). This retrospective study included patients who received concomitant chemoradiotherapy (CCRT) with cisplatin + etoposide regimen due to locally advanced stage IIIA/B NSCLC. The study included a total of 115 cases, consisting of 110 (95.7%) male and 5 (4.2%) female patients. The mean age of the patients was 61.3 ± 10.4 (22-82) years. ROC curve generated by MPV for OS yielded an AUC of 0.746 (95% CI 0.659-0.833), (p < 0.001). MPV was detected as >9 fL with a sensitivity of 74.4% and a specificity of 72.0%. In patients with stage IIIA, median OS was 45.0 months (95% CI 17.3-74.1) and 21 months (95% CI 10.6-31.3) in groups with MPV > 9.0 fL and ≤9.0 fL, respectively (p = 0.013). In patients with stage IIIB, median OS was 44.0 months (95% CI 13.8-60.6) and 16 months (95% CI 9.5-22.4) in groups with MPV > 9.0 fL and ≤9.0 fL, respectively (p = 0.036). ECOG performance score, total platelet count, and MPV were found as the most significant independent factors affecting survival (p < 0.001, p = 0.008, and, p = 0.034, respectively). In this study, we showed that decreased pre-treatment MPV was an independent risk factor for survival in NSCLC patients who were administered CCRT. As part of routine complete blood count panel, MPV may represent one of the easiest measuring tools as an independent prognostic marker for survival in locally advanced NSCLC.
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Affiliation(s)
- Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Medical School, 65030, Van, Turkey.
| | - Saban Secmeler
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Serdar Arici
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Caglayan Geredeli
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Nurgul Yasar
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Cumhur Demir
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Ferdi Aksaray
- Department of Radiation Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
| | - Sener Cihan
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, 34384, Istanbul, Turkey
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18
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Shi L, Li Y, Yu T, Wang Z, Zhou C, Xing W, Xu G, Tong B, Zheng Y, Zhou J, Huang P. Predictable Resistance and Overall Survival of Gemcitabine/Cisplatin by Platelet Activation Index in Non-Small Cell Lung Cancer. Med Sci Monit 2018; 24:8655-8668. [PMID: 30498189 PMCID: PMC6284361 DOI: 10.12659/msm.911125] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Background Gemcitabine/cisplatin (GP) resistance displays a negative role in treating advanced and metastatic non-small cell lung cancer (NSCLC). Several studies found that the association existed between platelets and cancer antigen 125 (CA125) with anticancer drugs. But the exact correlation between GP resistance and platelet activation index remains poorly understood. Material/Methods Pre-chemotherapy platelet activation index and CA125 were retrospectively evaluated in 169 advanced and metastatic NSCLC patients. All variables were screened by chi-square test and then evaluated by log-rank test. Survival curves were generated by Kaplan-Meier analysis. Univariate and multivariate survival analysis were performed by using Cox proportional hazards model. Results The overall rate of GP resistance for NSCLC patients was 72.19%. Mean platelet volume (MPV) and plateletcrit (PCT) are negative predictors of GP resistance adenocarcinoma [Odds ratio (OR): 5.81, 95% confidence interval (CI): 1.082–31.195, P=0.004] and squamous cell carcinoma (PCT: R: 3.517, 95% CI: 1.087–11.387, P=0.036), respectively. But both were an independent factor associated with overall survival (OS). Moreover, only CA125 was a dependent factor associated with OS for squamous cell carcinoma [OS: hazard ratio (HR): 1.741, 95% CI: 1.002–3.024, P=0.049; GP resistance: OR: 4.862, 95% CI: 1.437–16.448, P=0.011]. Conclusions Platelet activation index will be a potential marker for predicting GP resistance. Besides, CA125 ≥16.9 could be used as a potential marker for predicting GP resistance and OS, which was more sensitive than CA125 ≥35 for squamous cell carcinoma.
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Affiliation(s)
- Liang Shi
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
| | - Yiming Li
- Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, Institute of Drug Metabolism and Drug Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Tingting Yu
- Xihu District Hangzhou SanDu Town Community Health Service Center, Hangzhou, Zhejiang, China (mainland)
| | - Zeng Wang
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
| | - Chenxi Zhou
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
| | - Wenxiu Xing
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
| | - Gaoqi Xu
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
| | - BingLei Tong
- Cell-Land Biological Technology, Hangzhou, Zhejiang, China (mainland)
| | - Yingchao Zheng
- Pharmacy College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland)
| | - Jie Zhou
- Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, Institute of Drug Metabolism and Drug Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Ping Huang
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (mainland)
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Mean Platelet Volume, Red Cell Distribution Width, and Neutrophil-to-Lymphocyte Ratio Before and After Surgery in Patients With Carotid Body Tumors. J Craniofac Surg 2018; 28:e649-e653. [PMID: 28872499 DOI: 10.1097/scs.0000000000003786] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
OBJECTIVE Carotid body tumors (CBTs) are rare hypervascular benign tumors that originate from the paraganglia at the carotid bifurcation. The red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and mean platelet volume (MPV) may serve as markers in inflammatory, cardiovascular, and neoplastic diseases. However, their prognostic value in CBTs is unknown. The purpose of this study was to assess the leukocyte count, MPV, RDW, and NLR before and after surgery in patients with CBTs. METHODS This retrospective trial included data from 80 patients with CBTs and 65 age-matched healthy controls. The leukocyte, neutrophil, lymphocyte and platelet counts, RDW, and MPV were extracted and NLR was calculated from the complete blood count results of participants. RESULTS The leukocyte and neutrophil counts as well as RDW levels were significantly increased in patients with CBTs compared with healthy controls (P = 0.005, P = 0.003, and P = 0.026; respectively). Patients with CBTs had lower lymphocytes counts (P = 0.241) and higher NLRs (P = 0.054); however, the difference was statistically insignificant. Moreover, no statistically significant difference was detected between groups in terms of platelet counts and MPV levels. Furthermore, the leukocyte count, platelet numbers, MPV, RDW, and NLR levels in patients with CBTs were not statistically significant after surgery (all; P > 0.05). CONCLUSION This is the first study that documents the increased RDW levels and leukocyte count in patients with CBTs. The combined use of RDW and the leukocyte count along with other clinical assessments can be used as a biomarker for CBTs. Further clinical trials with larger cases series are required to determine the actual predictive roles of these systemic biomarkers.
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Abstract
Platelets are equipped with RNA processing machineries, such as pre-mRNA splicing, pre-miRNA processing, and mRNA translation. Since platelets are devoid of a nucleus, most RNA transcripts in platelets are derived from megakaryocytes during thrombocytogenesis. However, platelets can also ingest RNA molecules during circulation and/or interaction with other cell types. Since platelets were first described by Bizzozero in 1881, their well-established role in hemostasis and thrombosis has been intensively studied. However, in the past decades, the list of biological processes in which platelets play an important role keeps expanding. In this review, we discuss how platelet RNA biomarker signatures can be altered in the presence of cancer.
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Affiliation(s)
- Nik Sol
- Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. .,Brain Tumor Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
| | - Thomas Wurdinger
- Brain Tumor Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.,Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA
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21
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Zhang R, Guo H, Xu J, Li B, Liu YJ, Cheng C, Zhou C, Zhao Y, Liu Y. Activated platelets inhibit hepatocellular carcinoma cell differentiation and promote tumor progression via platelet-tumor cell binding. Oncotarget 2018; 7:60609-60622. [PMID: 27542264 PMCID: PMC5312405 DOI: 10.18632/oncotarget.11300] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Accepted: 07/26/2016] [Indexed: 12/12/2022] Open
Abstract
Lack of differentiation in hepatocellular carcinoma (HCC) is associated with increased circulating platelet size. We measured platelet activation and plasma adenosine diphosphate (ADP) levels in HCC patients based on differentiation status. Local platelet accumulation and platelet-hepatoma cell binding were measured using immunohistochemistry (IHC) or flow cytometry. Using a xenograft assay in NON/SCID mice, we tested the effects of the anti-platelet drug clopidogrel on platelet activation, platelet infiltration, platelet-tumor cell binding and tumor cell differentiation. HCC patients with poor differentiation status displayed elevated platelet activation and higher ADP levels. Platelets accumulated within poorly differentiated tissues and localized at hepatoma cell membranes. Platelet-tumor cell binding was existed in carcinoma tissues, largely mediated by P-selectin on platelets. NOD/SCID mice with xenograft tumors also exhibited increased platelet activation and platelet-tumor cell binding. Clopidogrel therapy triggered hepatoma cell differentiation by attenuating platelet activation and platelet-tumor cell binding. TCF4 knockdown promoted HepG-2 cell differentiation and inhibited tumor formation, and TCF4 could be the potential downstream target for clopidogrel therapy.
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Affiliation(s)
- Rongfeng Zhang
- Institute of Heart and Vascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Huishu Guo
- Department of Central Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jingchao Xu
- Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Bing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yue-Jian Liu
- Department of Central Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Cheng Cheng
- Translational Research on Neurological Diseases Center, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Chunyan Zhou
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yongfu Zhao
- Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yang Liu
- Institute of Heart and Vascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, China
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22
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Batmaz SB. Simple Markers for Systemic Inflammation in Pediatric Atopic Dermatitis Patients. Indian J Dermatol 2018; 63:305-310. [PMID: 30078874 PMCID: PMC6052751 DOI: 10.4103/ijd.ijd_427_17] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Atopic dermatitis is a dermatological disease characterized by chronic inflammation. In recent years, systemic inflammation is also mentioned along with local inflammation for its pathogenesis. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and mean platelet volume (MPV) are nonspecific indicators of systemic inflammation, and they were shown to be associated with the disease and its prognosis in allergic or nonallergic diseases. Aims and Objectives: The aim of this study was to evaluate the values of NLR, PLR, and MPV in atopic dermatitis patients and also to investigate the associations of them with the atopic dermatitis disease severity and duration. Materials and Methods: Two hundred and fifty-two atopic dermatitis patients and 75 control group individuals were included in the study. Mean/median values of NLR, PLR, and MPV were compared among patients and controls, severity groups classified according to SCORing Atopic Dermatitis (SCORAD) and intrinsic and extrinsic groups. Correlation of disease duration and SCORAD with NLR, PLR, and MPV values were examined. Disease duration and its association with NLR were evaluated by correlation and linear regression analysis. Results: Mean NLR and median PLR values of atopic dermatitis patients were higher than those of controls (0.97 ± 0.69 and 80.86 [59.86–108.23], respectively). NLR and PLR values were found to be positively correlated with disease duration and NLR was positively associated with disease duration after adjustment. NLR value was also higher in the extrinsic group than the intrinsic group. Conclusion: Presence of systemic inflammation in the pathogenesis of atopic dermatitis was considered to be associated with increased NLR and PLR values. These parameters were also associated with disease duration and might vary between subtypes of atopic dermatitis. NLR and PLR were cheaper and easily accessible alternatives to the systemic inflammation biomarkers that were expensive and not accessible for all laboratories, particularly in economically disadvantaged countries.
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Affiliation(s)
- Sehra Birgül Batmaz
- Department of Pediatric Allergy and Clinical Immunology, Tokat State Hospital, Tokat, Turkey
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Park JW, Kim CH, Ha YC, Kim MY, Park SM. Count of platelet and mean platelet volume score: serologic prognostic factor in patients with oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2017; 43:305-311. [PMID: 29142864 PMCID: PMC5685859 DOI: 10.5125/jkaoms.2017.43.5.305] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 05/08/2017] [Accepted: 05/26/2017] [Indexed: 11/07/2022] Open
Abstract
Objectives TNM staging, especially for lymph node metastasis, is the scoring system most widely used among prognostic factors for cancer survival. Several biomarkers have been studied as serologic markers, but their specificity is low and clinical applications are difficult. This study aimed to establish a scoring system for patients with oral squamous cell carcinoma (OSCC) using platelet (PLT) and mean platelet volume (MPV) levels measured postoperatively and to evaluate their significance as prognostic factors. Materials and Methods We studied 40 patients admitted to the Department of Oral and Maxillofacial Surgery of Dankook University Hospital who were diagnosed with primary OSCC histopathologically between May 2006 and May 2012. Clinical pathological information obtained from the medical records of each patient included age, sex, height, weight, tumor location, degree of differentiation, tumor diameter, lymph node metastasis, TNM stage, and other test values including white blood cell, MPV, PLT, C-reactive protein (CRP), and albumin obtained through a test conducted within 7 days before surgery. Count of platelet (COP)-MPV Score: Patients with both PLT and MPV values below the cut-off values were defined as score 0 (group A). Patients with at least one of the two higher than the cut-off value were defined as score 1 (group B). Results Univariate analyses showed N-metastasis, COP-MPV (A vs B), PLT, platelet-lymphocyte ratio, and CRP were statistically significant prognostic factors. A multivariate Cox proportional hazards model showed N-metastasis (hazard ratio [HR] 6.227, P=0.016) and COP-MPV (A vs B) (HR 18.992, P=0.013) were independent prognostic factors with a significant effect on survival. Conclusion COP-MPV score is a simple and cost-effective test method and is considered a more effective prognostic factor than other considered factors in predicting the prognosis of OSCC patients.
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Affiliation(s)
- Jae Woo Park
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea
| | - Chul-Hwan Kim
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea
| | - Yong Chan Ha
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea
| | - Moon Young Kim
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea
| | - Sung Min Park
- Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, Korea
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Fuentes HE, Paz LH, Wang Y, Oramas DM, Simons CR, Tafur AJ. Performance of Current Thromboembolism Risk Assessment Tools in Patients With Gastric Cancer and Validity After First Treatment. Clin Appl Thromb Hemost 2017; 24:790-796. [PMID: 28884610 DOI: 10.1177/1076029617726599] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Patients with gastric cancer (GC) are at higher risk of thromboembolism when compared to other solid tumors. We aim to determine the predictive performance of current venous thromboembolism (VTE) predictive tools and their variability and validity after first treatment. Single institution cohort of GC-treated patients (2010*15). We abstracted predictive tools, validated for VTE prediction in patient with cancer; including the Khorana Score (KRS), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR). The primary outcome was CAT prediction. We included 112 patients who were predominantly men (66%), 58 (51-64)-year-olds, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (9.5-42.6). The VTE occurrence was 12%. The median time from diagnosis to VTE occurrence was 59 days (36-258). In our cohort, performance status (PS; hazard ratio [HR], 8.02; 95% confidence interval [CI], 2.37-27.14; P < .01) was an independent predictor of VTE whereas KRS (univariate HR, 2.3; 95% CI, 0.7-7.4; P = .17), PLR (univariate HR, 0.8; 95% CI, 0.2-3.1; P = .8), and NLR (univariate HR, 0.8; 95% CI, 0.3-2.5; P = .8) at baseline were not associated with VTE risk. The posttreatment KRS was an independent predictor of VTE (HR, 3.69; 95% CI, 1.17-11.65; P = .25) along with PS (HR, 7.58; 95% CI, 2.27-25.33; P = .01). Posttreatment KRS appears as a valid tool to identify patients with GC at high risk of VTE after first cancer treatment.
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Affiliation(s)
- Harry E Fuentes
- 1 Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - L H Paz
- 1 Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - Y Wang
- 1 Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - D M Oramas
- 2 Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - C R Simons
- 1 Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - A J Tafur
- 3 Cardiology-Vascular Medicine, Northshore University Healthsystem, Evanston, IL, USA
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25
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Gao L, Zhang H, Zhang B, Zhang L, Wang C. Prognostic value of combination of preoperative platelet count and mean platelet volume in patients with resectable non-small cell lung cancer. Oncotarget 2017; 8:15632-15641. [PMID: 28152504 PMCID: PMC5362511 DOI: 10.18632/oncotarget.14921] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 12/13/2016] [Indexed: 11/25/2022] Open
Abstract
The aim of the present study was to investigate the prognostic value of the combination of preoperative platelet count (PLT) and mean platelet volume (MPV) in patients with primary operable non-small cell lung cancer (NSCLC). We retrospectively analysed data from 546 patients with NSCLC who underwent complete resection at our institution from 2006 to 2010. Patients’ clinical characteristics and laboratory test data at initial diagnosis were collected. Both preoperative PLT and MPV (COP-MPV) were calculated on the basis of the data obtained using the recommended cut-off values of 300 × 109 L−1 and 11.0 fL, respectively. Patients with both an elevated PLT (≥300× 109 L−1) and a decreased MPV (<11.0 fL) were assigned a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. Multivariate analysis of the 9 clinical laboratory variables selected by univariate analysis revealed that preoperative COP-MPV was a significantly independent prognostic factor for overall survival (OS) (hazard ratio, 1.775; 95% confidence interval, 1.500–2.101; P< 0.001) and disease-free survival (DFS) (hazard ratio, 1.719; 95% confidence interval, 1.454–2.033; P< 0.001). In subgroup analyses for tumour pathological stage (I/II/IIIA) patients, we found that the level of COP-MPV was significantly associated with OS and DFS in each subgroup (P< 0.001, P< 0.001, P<0.001 for OS and P<0.001, P< 0.001, P=0.001 for DFS, respectively). In conclusion, the preoperative COP-MPV is a promising predictor of postoperative survival in patients with NSCLC and could classify these patients into three independent groups before surgery.
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Affiliation(s)
- Liuwei Gao
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin, China
| | - Hua Zhang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin, China
| | - Bin Zhang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin, China
| | - Lianmin Zhang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin, China
| | - Changli Wang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, Tianjin, China
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26
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Repetto O, De Re V. Coagulation and fibrinolysis in gastric cancer. Ann N Y Acad Sci 2017; 1404:27-48. [PMID: 28833193 DOI: 10.1111/nyas.13454] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 07/12/2017] [Accepted: 07/25/2017] [Indexed: 12/12/2022]
Abstract
Coagulation is a highly conserved process occurring after an injury to a blood vessel and resulting in hemostasis. In the thrombus microenvironment, finely orchestrated events restore vessel integrity through platelet activation, adhesion, and aggregation (primary hemostasis), followed by the coagulation cascades, thrombin generation, and fibrin clot deposition (secondary hemostasis). Several studies on cancer have provided insight into dramatic changes to coagulation-related events (i.e., fibrin clot deposition, fibrinolysis) during tumor pathogenesis, progression, and metastasis, in addition to a tumor-driven systemic activation of hemostasis and thrombosis (Trousseau's syndrome). Diverse molecular and cellular effectors participate in the cross talk between hemostasis and tumors. Here, we focus on some aspects of the interconnection between cancer biology and hemostatic components, with particular attention to some key coagulation-related proteins (e.g., tissue factor, thrombin, fibrinogen, and D-dimers) in the particular case of gastric cancer (GC). Recent advances in deciphering the complex molecular link between GC and the coagulation system are described, showing their important roles in better management of patients affected by GC.
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Affiliation(s)
- Ombretta Repetto
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano National Cancer Institute, Aviano (PN), Italy
| | - Valli De Re
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano National Cancer Institute, Aviano (PN), Italy
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27
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Best MG, Vancura A, Wurdinger T. Platelet RNA as a circulating biomarker trove for cancer diagnostics. J Thromb Haemost 2017; 15:1295-1306. [PMID: 28671345 DOI: 10.1111/jth.13720] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Platelets are multifunctional cell fragments, circulating in blood in high abundance. Platelets assist in thrombus formation, sensing of pathogens entering the blood stream, signaling to immune cells, releasing vascular remodeling factors, and, negatively, enhancing cancer metastasis. Platelets are 'educated' by their environment, including in patients with cancer. Cancer cells appear to initiate intraplatelet signaling, resulting in splicing of platelet pre-mRNAs, and enhance secretion of cytokines. Platelets can induce leukocyte and endothelial cell modeling factors, for example, through adenine nucleotides (ATP), thereby facilitating extravasation of cancer cells. Besides releasing factors, platelets can also sequester RNAs and proteins released by cancer cells. Thus, platelets actively respond to queues from local and systemic conditions, thereby altering their transcriptome and molecular content. Platelets contain a rich repertoire of RNA species, including mRNAs, small non-coding RNAs and circular RNAs; although studies regarding the functionality of the various platelet RNA species require more attention. Recent advances in high-throughput characterization of platelet mRNAs revealed 10 to > 1000 altered mRNAs in platelets in the presence of disease. Hence, platelet RNA appears to be dynamically affected by pathological conditions, thus possibly providing opportunities to use platelet RNA as diagnostic, prognostic, predictive, or monitoring biomarkers. In this review, we cover the literature regarding the platelet RNA families, processing of platelet RNAs, and the potential application of platelet RNA as disease biomarkers.
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Affiliation(s)
- M G Best
- Department of Neurosurgery, VU University Medical Center, Amsterdam, the Netherlands
- Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
- Brain Tumor Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
| | - A Vancura
- Department of Neurosurgery, VU University Medical Center, Amsterdam, the Netherlands
- Brain Tumor Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
| | - T Wurdinger
- Department of Neurosurgery, VU University Medical Center, Amsterdam, the Netherlands
- Brain Tumor Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
- Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA
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28
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Lack of association between platelet indices and disease stage in osteosarcoma at diagnosis. PLoS One 2017; 12:e0174668. [PMID: 28384168 PMCID: PMC5383043 DOI: 10.1371/journal.pone.0174668] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Accepted: 03/13/2017] [Indexed: 12/21/2022] Open
Abstract
Purpose The purpose of this study was to investigate the relationship between platelet indices [mean platelet volume (MPV), platelet count (PLT), platelet distribution width (PDW) and plateletcrit (PCT)] at diagnosis in osteosarcoma. Methods The information of 233 patients with osteosarcoma at diagnosis between 2007 and 2015 was retrospectively reviewed. Clinical parameters such as gender, age, size and site of tumor, and tumor necrosis rate after neoadjuvant chemotherapy were analyzed. Results No significant difference was noted in the mean values of MPV, PLT, PDW and PCT among stage I, II and III patients. In localized patients, the median disease-free survival (DFS) values were 42 and 22 months in the PLT<300×109/L and ≥300×109/L groups, respectively, but the difference was not statistically significant (P = 0.2611). No difference in the DFS among the three different levels of MPV was observed. Conclusion No significantly different platelet indices were noted among the different stages. Although a shorter median DFS was found in localized patients with PLT≥300×109/L, there was still a lack of strong evidence to demonstrate the association between platelet indices and osteosarcoma.
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Omar M, Tanriverdi O, Cokmert S, Oktay E, Yersal O, Pilancı KN, Menekse S, Kocar M, Sen CA, Ordu C, Goksel G, Meydan N, Barutca S. Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer. CLINICAL RESPIRATORY JOURNAL 2017; 12:922-929. [PMID: 28026133 DOI: 10.1111/crj.12605] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 11/28/2016] [Accepted: 12/20/2016] [Indexed: 01/21/2023]
Abstract
OBJECTIVES In this study, they investigated whether mean thrombocyte volume (MPV) and MPV/platelet count ratio have a prognostic significance in advanced NSCLC or not. METHODS A total of 496 NSCLC patients at stage IIIB/IV and did not meet exclusion criteria were included in the study. The demographic features (age, gender, smoking habit), clinical characteristics (performance status, weight loss, disease stage, first-line treatment regimen), laboratory tests (levels of hemoglobin, lactate dehydrogenase and calcium as well as MPV, MPV/platelet count ratio and counts of white blood cell, platelet), and histological features (histologic type, tumor grade) were recorded. RESULTS The MPV levels of all patients were determined as 10.2 {plus minus} 3.4 (range, 6.4-14.1 fL). With ROC curve analysis, the MPV/PC ratio was associated with a sensitivity of 67.8% and a specificity of 84.8% at a cutoff value of 0.47424 for presence of brain metastasis at the time of diagnosis. Univariate analysis showed that OS was significantly shorter in the group with an increased MPV level than in the other group (median OS time 6.8 months vs. 11.5 months, log-rank, P = .032). Multivariate analysis confirmed that an increased MPV level was an independent poor prognostic factor for OS (HR: 1.704, 95% CI: 1.274-3.415, P = .014). CONCLUSIONS Unlike results of previous studies, the study showed that increased MPV was an important prognostic factor in patients with NSCLC. Hence, an increased MPV level may be used as a prognostic biomarker to estimate for poor overall survival in patients with NSCLC.
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Affiliation(s)
- Muhyettin Omar
- Department of Internal Medicine and Medical Oncology, Sitki Kocman University Faculty of Medicine, Mugla, Turkey
| | - Ozgur Tanriverdi
- Department of Internal Medicine and Medical Oncology, Sitki Kocman University Faculty of Medicine, Mugla, Turkey
| | - Suna Cokmert
- Department of Medical Oncology, Kent Hospital, Izmir, Turkey
| | - Esin Oktay
- Department of Medical Oncology, Adnan Menderes University Faculty of Medicine, Aydin, Turkey
| | - Ozlem Yersal
- Department of Medical Oncology, Education and Research Hocpital, Samsun, Turkey
| | - Kezban Nur Pilancı
- Department of Medical Oncolgy, Bilim University Faculty of Medicine, Istanbul, Turkey
| | - Serkan Menekse
- Department of Medical Oncology, Celal Bayar University Faculty of Medicine, Manisa, Turkey
| | - Muharrem Kocar
- Department of Medical Oncology, Education and Research Hospital, Sanliurfa, Turkey
| | - Cenk Ahmet Sen
- Department of Radiation Oncology, Izmir University Medical Park Hospital, Izmir, Turkey
| | - Cetin Ordu
- Department of Medical Oncolgy, Bilim University Faculty of Medicine, Istanbul, Turkey
| | - Gamze Goksel
- Department of Medical Oncology, Celal Bayar University Faculty of Medicine, Manisa, Turkey
| | - Nezih Meydan
- Department of Medical Oncology, Adnan Menderes University Faculty of Medicine, Aydin, Turkey
| | - Sabri Barutca
- Department of Medical Oncology, Adnan Menderes University Faculty of Medicine, Aydin, Turkey
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Hirahara N, Matsubara T, Kawahara D, Mizota Y, Ishibashi S, Tajima Y. Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma. Int J Clin Oncol 2016; 21:909-919. [PMID: 27154178 PMCID: PMC5055579 DOI: 10.1007/s10147-016-0986-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 04/25/2016] [Indexed: 01/20/2023]
Abstract
BACKGROUND It is now widely recognized that outcomes in cancer patients are not determined by their tumor characteristics alone. In this study, we retrospectively analyzed the clinical data of esophageal cancer patients to evaluate the impact of red blood cell distribution width (RDW), platelet distribution width (PDW), and mean platelet volume (MPV) on cancer-specific survival (CSS). STUDY DESIGN We retrospectively reviewed a database of 144 consecutive patients who underwent curative esophagectomy for esophageal squamous cell carcinoma at our institute between 2006 and 2014. RESULT In multivariate analysis, pathological stage (pStage) (p = 0.0002) and a high RDW (p = 0.0300) were found to be independently associated with poor survival. Patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.004). Among non-elderly patients, multivariate analysis demonstrated that pStage (p = 0.0120), and a high RDW (p = 0.0092) were independent risk factors for a worse prognosis. In addition, non-elderly patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.0003). On the other hand, univariate analysis demonstrated that pStage (p = 0.0008) was the only significant risk factor for a poor prognosis in elderly patients. CONCLUSIONS We confirmed that a high RDW was significantly associated with the CSS of esophageal cancer patients after curative esophagectomy. Furthermore, in non-elderly patients, a high RDW was a significant and independent predictor of poor survival.
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Affiliation(s)
- Noriyuki Hirahara
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
| | - Takeshi Matsubara
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Daisuke Kawahara
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Yoko Mizota
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Shuichi Ishibashi
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Yoshitsugu Tajima
- Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
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31
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Au AE, Josefsson EC. Regulation of platelet membrane protein shedding in health and disease. Platelets 2016; 28:342-353. [PMID: 27494300 DOI: 10.1080/09537104.2016.1203401] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Extracellular proteolysis of platelet plasma membrane proteins is an event that ensues platelet activation. Shedding of surface receptors such as glycoprotein (GP) Ibα, GPV and GPVI as well as externalized proteins P-selectin and CD40L releases soluble ectodomain fragments that are subsequently detectable in plasma. This results in the irreversible functional downregulation of platelet receptor-mediated adhesive interactions and the generation of biologically active fragments. In this review, we describe molecular insights into the regulation of platelet receptor and ligand shedding in health and disease. The scope of this review is specially focused on GPIbα, GPV, GPVI, P-selectin and CD40L where we: (1) describe the basic physiological regulation of expression and shedding of these proteins in hemostasis illustrate alterations in receptor expression during (2) apoptosis and (3) ex vivo storage relevant for blood banking purposes; (4) discuss considerations to be made when analyzing and interpreting shedding of platelet membrane proteins and finally; (5) collate clinical evidence that quantify these platelet proteins during disease.
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Affiliation(s)
- Amanda E Au
- a The Walter and Eliza Hall Institute of Medical Research, Cancer & Haematology Division , 1G Royal Parade, Melbourne , Australia.,b Department of Medical Biology , The University of Melbourne , Melbourne , Australia
| | - Emma C Josefsson
- a The Walter and Eliza Hall Institute of Medical Research, Cancer & Haematology Division , 1G Royal Parade, Melbourne , Australia.,b Department of Medical Biology , The University of Melbourne , Melbourne , Australia
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32
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Fuentes E, Palomo I, Rojas A. Cross-talk between platelet and tumor microenvironment: Role of multiligand/RAGE axis in platelet activation. Blood Rev 2016; 30:213-221. [PMID: 26723842 DOI: 10.1016/j.blre.2015.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 10/02/2015] [Accepted: 11/30/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Eduardo Fuentes
- Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule R09I2001, Talca, Chile.
| | - Iván Palomo
- Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule R09I2001, Talca, Chile
| | - Armando Rojas
- Biomedical Research Laboratories, Medicine Faculty, Catholic University of Maule, Talca, Chile.
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Combination of platelet count and mean platelet volume (COP-MPV) predicts postoperative prognosis in both resectable early and advanced stage esophageal squamous cell cancer patients. Tumour Biol 2016; 37:9323-31. [PMID: 26779631 PMCID: PMC4990601 DOI: 10.1007/s13277-015-4774-3] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 12/29/2015] [Indexed: 12/18/2022] Open
Abstract
The aim of this study is to search the most powerful prognostic factor from routine blood test for esophageal squamous cell cancer (ESCC) patients. Multiple laboratory tests were evaluated including those reflecting red blood cell parameters (hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)), platelet morphological parameters (mean platelet volume (MPV) and platelet count (PLT)), blood coagulation status (D-dimer), and tumor biomarker (CA19-9). Known inflammatory indices (NLR and PLR) were also calculated. A total of 468 patients who were diagnosed with ESCC between December 2005 and December 2008 were retrospectively analyzed in this study. By utilizing univariate and multivariate Cox proportional hazard analyses, we found that PLT and MPV were significantly associated with overall survival (OS) and disease-free survival (DFS) of ESCC patients, with optimal cutoff values of 212 and 10.6, respectively. Moreover, the combination of the preoperative PLT and MPV (COP-MPV) was calculated as follows: patients with both PLT (≥212 × 10(9) L(-1)) and MPV (≥10.6 fL) elevation were assigned a score of 2, and patients with one or neither were assigned a score of 1 and 0. The COP-MPV was an independent prognostic factor for OS (hazard ratio (HR) 0.378, 95 % confidence interval (CI) 0.241 to 0.593, P < 0.001, 0/2) and DFS (HR 0.341, 95 % CI 0.218 to 0.534, P < 0.001, 0/2) in multivariate analyses. In subgroup analyses for early (stages I and II) and locally (stage III) advanced stage patients, COP-MPV was found significantly associated with OS and DFS in each group (P = 0.025 and P = 0.018 for OS and P = 0.029 and P = 0.002 for DFS). In conclusion, we considered that COP-MPV is a promising predictor for postoperative survival in ESCC patients.
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Li JY, Li Y, Jiang Z, Wang RT, Wang XS. Elevated mean platelet volume is associated with presence of colon cancer. Asian Pac J Cancer Prev 2015; 15:10501-4. [PMID: 25556499 DOI: 10.7314/apjcp.2014.15.23.10501] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Colon cancer is the second most common cancer in developed countries. Activated platelets play a key role in inflammation and atherothrombosis, with mean platelet volume (MPV) is an early marker of platelet activation. The aim of the study was to clarify the relevance of MPV in patients with colon cancer. MATERIALS AND METHODS We measured MPV levels in 128 patients with colon cancer before and after surgery, and 128 controls matched for age, gender, body mass index (BMI) and smoking status. The odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer were calculated using multivariate logistic regression analyses across MPV quartiles. RESULTS Patients with colon cancer had higher MPV compared with controls. Surgical tumor resection resulted in a significant decrease in MPV levels (11.4 fL vs 10.7 fL; p<0.001). A positive correlation between MPV and tumor-nodule-metastases (TNM) stage was found. Furthermore, after adjusting for other risk factors, the ORs (95%CIs) for colon cancer according to MPV quartiles were 1.000, 2.238 (1.014-4.943), 3.410 (1.528-7.613), and 5.379 (2.372-12.198), respectively. CONCLUSIONS The findings show that patients with colon cancer have higher MPV levels compared with controls, and these are reduced after surgery. In addition, MPV was found to be independently associated with the presence of colon cancer. Further studies are warranted to assess the utility of MPV as a novel diagnostic screening tool for colon cancer.
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Affiliation(s)
- Jia-Ying Li
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China E-mail : ,
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Bayhan Z, Zeren S, Ozbay I, Kahraman C, Yaylak F, Tiryaki C, Ekici M. Mean Platelet Volume as a Biomarker for Thyroid Carcinoma. Int Surg 2015; 101:50-53. [PMID: 26160507 DOI: 10.9738/intsurg-d-15-00123.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
AbstractObjective: This study aimed to determine the relationship between MPV and thyroid malignancy by comparing patients who underwent surgery for benign or malignant thyroid diseases. BACKGROUND Mean platelet volume (MPV) is a useful early indicator of platelet activation. Platelets differ in terms of functional activity and size. Large platelets are relatively new, more reactive and produce more thrombogenic factors. Therefore, in conditions that involve increased platelet activation, an increase in the proportion of young platelets and MPV is expected. PATIENTS AND METHODS This study involved 146 patients who underwent total thyroidectomy because of benign (99 patients) or malignant (47 patients) diseases of the thyroid. Data on age, sex, MPV, white blood cell (WBC) count, hemoglobin level and platelet count were collected retrospectively. RESULTS MPV was significantly higher in patients with malignant thyroid diseases than in those with benign thyroid diseases. Age, sex, hemoglobin level, WBC count and platelet count did not significantly differ between the two groups. CONCLUSION MPV was significantly higher in patients with thyroid malignancies than in patients with benign thyroid diseases. We propose that MPV might be an important predictive factor for thyroid malignancies. Further prospective studies with a larger number of patients in high-volume endocrine surgery centers are required to confirm our findings.
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Affiliation(s)
- Zulfu Bayhan
- b Dumlupinar University, Faculty of Medicine, Kutahya, 43100, Turkey
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Abstract
We have recently performed the first comprehensive study of the potential immunosuppressive role of soluble CD40L (sCD40L). In addition, we demonstrated that serum sCD40L can potentially be used as an indicator of response to anticancer therapy, and/or to better identify those patients who would have best chances to benefit from tumor-targeting vaccines or other therapeutic modalities.
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Affiliation(s)
- Jeffrey Schlom
- Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA
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Gunduz S, Mutlu H, Uysal M, Coskun HS, Bozcuk H. Elucidating the correlation between treatment with tyrosine kinase inhibitors and mean platelet volume in patients with metastatic renal cell cancer. Oncol Lett 2014; 8:2249-2252. [PMID: 25289104 PMCID: PMC4186555 DOI: 10.3892/ol.2014.2495] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 08/07/2014] [Indexed: 12/21/2022] Open
Abstract
Patients with cancer are at increased risk of thrombosis. Additionally, an increased mean platelet volume (MPV) has been demonstrated to be associated with thromboembolism. Tyrosine kinase inhibitors (TKIs) may modulate the activation of systemic coagulation in cancer patients, rendering them more susceptible to thromboembolism. The aim of the current study was to investigate the association between antiangiogenic TKIs and MPV. A total of 45 patients with metastatic renal cell carcinoma (RCC), who were treated with TKIs and were patients at the Akdeniz University Hospital and Afyon Kocatepe University Ahmet Necdet Sezer Research and Practice Hospital, were retrospectively reviewed. The results prior to treatment and after three months for the MPV values and platelet levels were evaluated. The MPV values increased following the treatment with TKIs; however, no statistically significant difference was observed between the baseline and three month values (P=0.286). Conversely, a significant decrease was observed in the platelet levels following treatment (P=0.005). Treatment with TKIs in patients with metastatic RCC caused a modest increase in MPV, which is an indicator of thrombocytic reactivity; however, further studies are required to validate these results.
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Affiliation(s)
- Seyda Gunduz
- Department of Medical Oncology, Akdeniz University Hospital, Antalya 07070, Turkey
| | - Hasan Mutlu
- Department of Medical Oncology, Akdeniz University Hospital, Antalya 07070, Turkey
| | - Mukremin Uysal
- Department of Medical Oncology, Afyon Kocatepe University Ahmet Necdet Sezer Research and Practice Hospital, Afyon 3000, Turkey
| | - Hasan Senol Coskun
- Department of Medical Oncology, Akdeniz University Hospital, Antalya 07070, Turkey
| | - Hakan Bozcuk
- Department of Medical Oncology, Akdeniz University Hospital, Antalya 07070, Turkey
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Chung HW, Lim JB. Clinical significance of elevated serum soluble CD40 ligand levels as a diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma. J Transl Med 2014; 12:102. [PMID: 24745825 PMCID: PMC4021610 DOI: 10.1186/1479-5876-12-102] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 04/08/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND CD40-CD40 ligand (CD40L) interaction is considered to contribute to the promotion of prothrombotic responses and production of angiogenesis-associated factor in addition to adaptive immune responses. Recently, the role of soluble CD40L (sCD40L) has gained interest in cancer, although its exact functions remain unknown. This study evaluated the clinical significance of sCD40L in patients with pancreatic ductal adenocarcinoma (PDAC) and validated its utility as a PDAC diagnostic and prognostic biomarker. METHODS Serum sCD40L levels were measured by chemiluminescent immunoassay and compared among normal, chronic pancreatitis (CP, high-risk), and PDAC group in both training (n=25 per group) and independent validation (n=30, 30, and 55, respectively) datasets through one-way ANOVA test with the post-hoc Bonferroni method. To evaluate the diagnostic potential of serum sCD40L for PDAC, receiver operating characteristic (ROC) curves were generated and logistic regression analysis was conducted. To investigate the sCD40L-assoicated cytokines/chemokines in PDAC, cytokines/chemokines levels were analyzed by a MILLIPLEX MAP Human Cytokine/Chemokine Kit. To assess the prognostic potentials of sCD40L, Kaplan-Meier survival curve and Cox proportional-hazards regression analysis were applied. RESULTS Serum sCD40L levels were significantly higher in PDAC group compared with non-cancer groups in both training (p<0.05) and validation (p<0.05) datasets. Clinically, serum sCD40L closely correlated with unresectability (γs=0.342, p=0.011) and distant metastasis (γs=0.294, p=0.030) of PDAC. ROC curve and logistic regression analysis demonstrated the remarkable predictive potentials of serum sCD40L for PDAC (80.0% sensitivity and 85.5% specificity at cut-off point, 0.45; logistic regression), superior to those of CA19-9 and CEA. According to cytokines/chemokines assay, serum sCD40L levels were closely correlated with serum levels of pro-angiogenic cytokines (EGF, VEGF, IL-8) and immunosuppressive cytokines (IL-6, IL-10, IL-1RA). Kaplan-Meier survival analysis demonstrated patients with high-serum sCD40L (>35,000 ng/ml) had a poorer prognosis than those with low-serum sCD40L (log-rank, p=0.015). Multivariate Cox regression analysis yielded a hazard ratio of 2.509 (95% CI, 1.038-6.067, p=0.041) for mortality in the high-serum sCD40L group. CONCLUSIONS Serum sCD40L is correlated with immunosuppression and angiogenesis in PDAC carcinogenesis/progression, and is a promising diagnostic and prognostic biomarker for PDAC superior to CA19-9 and CEA.
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Affiliation(s)
| | - Jong-Baeck Lim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Inagaki N, Kibata K, Tamaki T, Shimizu T, Nomura S. Prognostic impact of the mean platelet volume/platelet count ratio in terms of survival in advanced non-small cell lung cancer. Lung Cancer 2013; 83:97-101. [PMID: 24189108 DOI: 10.1016/j.lungcan.2013.08.020] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 08/25/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Mean platelet volume (MPV) is a platelet volume index. Classically, MPV was recognized as a hallmark of platelet activation. Recent studies have revealed that the MPV and MPV/platelet count (PC) ratio can predict long-term mortality in patients with ischemic cardio-vascular disease. In addition, these indices were correlated with the pathophysiological characteristics of patients with various disorders, including malignant tumors. PATIENTS AND METHODS We retrospectively analyzed various hematological indices of patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the contribution of platelet volume indices to survival in these patients. RESULTS A total of 268 patients were enrolled in the study. The median age of the patients was 68 years (range: 31-87 years). We compared various hematological indices between the NSCLC group and an age- and sex-matched comparator group. MPV was significantly decreased in the NSCLC group compared to the comparator group. In contrast, the PC was significantly increased in the NSCLC group. Consequently, the MPV/PC ratio was also decreased in the NSCLC group (0.397 vs. 0.501). In receiver operating characteristics (ROC) curve analysis, the MPV/PC ratio was associated with a sensitivity of 62.3% and a specificity of 74.6% at a cutoff value of 0.408730 (area under the curve [AUC], 0.72492)]. Univariate analysis revealed that overall survival (OS) was significantly shorter in the group with a low MPV/PC ratio than in the other group (median survival time [MST]: 10.3 months vs. 14.5 months, log-rank, P=0.0245). Multivariate analysis confirmed that a low MPV/PC ratio was an independent unfavorable predictive factor for OS (hazard ratio [HR]: 1.668, 95% confidence interval [CI]: 1.235-2.271, P=0.0008). CONCLUSION These data clearly demonstrate that the MPV/PC ratio was closely associated with survival in patients with advanced NSCLC.
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Affiliation(s)
- Noriko Inagaki
- First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-City, Osaka 570-8507, Japan
| | - Kayoko Kibata
- First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-City, Osaka 570-8507, Japan
| | - Takeshi Tamaki
- First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-City, Osaka 570-8507, Japan
| | - Toshiki Shimizu
- First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-City, Osaka 570-8507, Japan.
| | - Shosaku Nomura
- First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-City, Osaka 570-8507, Japan
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Ishige K, Osada N, Kosuge Y, Ito Y. [Involvement of endoplasmic reticulum stress in neurodegeneration after transient global ischemia-reperfusion]. Nihon Yakurigaku Zasshi 2013; 142:9-12. [PMID: 23842221 DOI: 10.1254/fpj.142.9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
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Kılınçalp S, Ekiz F, Başar O, Ayte MR, Coban S, Yılmaz B, Altınbaş A, Başar N, Aktaş B, Tuna Y, Erbiş H, Uçar E, Erarslan E, Yüksel O. Mean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer. Platelets 2013; 25:592-4. [PMID: 23537073 DOI: 10.3109/09537104.2013.783689] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. The early diagnosis of gastric cancer is fundamental in decreasing the mortality rates. It has been shown that MPV level is a sign of inflammation in hepatocellular carcinoma and pancreatic adenocarcinoma. The aim of this study is to examine whether MPV would be a useful inflammatory marker for differentiating gastric cancer patients from healthy controls. Thirty-one gastric cancer patients and 31 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. MPV level was significantly higher in pre-operative gastric cancer patients compared to healthy subjects (8.31 fL vs. 7.85; p: 0.007). ROC analysis suggested 8.25 fL as the cut-off value for MPV (AUC: 0.717, sensitivity: 61%, specificity: 81%). Surgical tumor resection resulted in a significant decrease in MPV level (8.31 fL vs. 7.55 fL; p: 0.001). No significant difference was found in MPV level between the post-operative group and control subjects. We did not find statistically significant difference between MPV and TNM stages. In conclusion, changes in MPV values may be used as an easily available biomarker for monitoring the healthy patients for GC risk and may prompt physicians to make an early diagnosis of GC.
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Affiliation(s)
- Serta Kılınçalp
- Department of Gastroenterology , Ankara Dışkapı Yıldırım Beyazıt Education and Research Hospital , Ankara , Turkey
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Matowicka-Karna J, Kamocki Z, Polińska B, Osada J, Kemona H. Platelets and inflammatory markers in patients with gastric cancer. Clin Dev Immunol 2013; 2013:401623. [PMID: 23554823 PMCID: PMC3608177 DOI: 10.1155/2013/401623] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2012] [Revised: 02/05/2013] [Accepted: 02/17/2013] [Indexed: 12/23/2022]
Abstract
The aim of the study was to assess the contribution of platelets and inflammatory markers in gastric cancer. We studied 50 patients. Taking into consideration the advancement of gastric cancer, patients were divided into 3 groups. Group (E)--13 patients with early gastric cancer, group (A)--18 patients with regionally advanced cancer, and group (M)--19 patients with metastatic cancer. The determinations were performed twice prior to surgery and after surgery. In patients with gastric cancer, there is an increase in IL-6 and IL-23 compared with the healthy group. The highest values of IL-6 were obtained in early cancer (more than 8-fold increase), which seems to confirm the presence of acute inflammation. The lowest value of both of these cytokines was obtained in patients with metastatic cancer. In all patients, regardless of tumor stage, there was an increase in the concentration of CRP. An increase of PLT, higher proportion of the percentage of large platelets (LPLT), and increased mean platelet volume (MPV) were observed in the process of disease development. A positive correlation between MPV and LPLT and the accompanying decrease in the concentration of proinflammatory cytokines indicates the presence of an existing relationship between the platelet morphological parameters and the inflammation process in the development of gastric cancer.
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Affiliation(s)
- Joanna Matowicka-Karna
- Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, J. Waszyngton 15a, 15-269 Bialystok, Poland.
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Matowicka-Karna J, Kamocki Z, Kemona H. Assessment of platelet activation and phagocytic activity in gastric cancer patients. World J Gastrointest Pathophysiol 2013; 4:12-7. [PMID: 23596550 PMCID: PMC3627834 DOI: 10.4291/wjgp.v4.i1.12] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Revised: 10/01/2012] [Accepted: 12/06/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the activation of platelets and their phagocytic activity in the course of gastric cancer.
METHODS: Forty-three gastric cancer patients were recruited to the study. The patients were divided into 3 groups depending on tumor stage. Group E included 6 patients with early gastric cancer; group A 18 patients with locally advanced cancer; and group M-19 with metastatic cancer. The investigations were performed twice, prior to surgery and 12-14 d afterwards.
RESULTS: The platelet count and the level of soluble platelet selectin (sP-selectin) were found to increase with the disease progression. The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients. Irrespective of tumor stage, a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects. Despite increased platelet count and stimulation of thrombocytopoiesis, the phagocytic functions of blood platelets were markedly impaired. Tumor development seems to impair metabolic processes.
CONCLUSION: A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.
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Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood 2012; 120:3030-8. [PMID: 22932804 DOI: 10.1182/blood-2012-05-427799] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Tumor cells can induce certain cytokines and soluble receptors that have a suppressive effect on the immune system. In this study, we showed that an extracellular portion of a membrane-bound ligand of CD40 (soluble CD40 ligand; sCD40L) was significantly elevated in the serum of cancer patients compared with healthy donors. In addition, PBMCs from cancer patients had a relatively larger population of myeloid-derived suppressor cells (MDSCs), defined as CD33(+)HLA-DR(-) cells, and these cells expressed higher levels of CD40. T-cell proliferation and IFN-γ production decreased when stimulated T cells were cocultured with an increased amount of autologous MDSCs. The addition of recombinant monomeric sCD40L enriched MDSCs and had an additive inhibitory effect on T-cell proliferation. PBMCs cultured in vitro with sCD40L also showed an expansion of regulatory T cells (CD4(+)CD25(high)Foxp3(+)), as well as induction of cytokines, such as IL-10 and IL-6. Moreover, sCD40L-induced enrichment of programmed death-1-expressing T cells was greater in cancer patients than in healthy donors. Preexisting sCD40L also inhibited IL-12 production from monocytes on activation. These data suggest that the higher levels of sCD40L seen in cancer patients may have an immunosuppressive effect.
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Varol E. Effect of mean platelet volume on thrombus formation in patients with cancer. Clin Appl Thromb Hemost 2012; 19:105. [PMID: 22826446 DOI: 10.1177/1076029612453764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Karaman K, Bostanci EB, Aksoy E, Kurt M, Celep B, Ulas M, Dalgic T, Surmelioglu A, Hayran M, Akoglu M. The predictive value of mean platelet volume in differential diagnosis of non-functional pancreatic neuroendocrine tumors from pancreatic adenocarcinomas. Eur J Intern Med 2011; 22:e95-8. [PMID: 22075321 DOI: 10.1016/j.ejim.2011.04.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Revised: 03/18/2011] [Accepted: 04/17/2011] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The aim of the present study is to evaluate in a retrospective manner the diagnostic value of mean platelet volume (MPV) in pancreatic adenocarcinomas and pancreatic neuroendocrine tumors (PNETs). PATIENTS AND METHODS A total of 92 patients, who were admitted for pancreatic adenocarcinoma (n=76) and PNET (n=16) between March 2007 and December 2009, were analyzed retrospectively for demographics and clinical information. RESULTS Thirty-nine patients (51.3%) had a resectable, whereas 37 patients (48.7%) had an unresectable pancreatic adenocarcinoma. Nine patients (56.3%) had a non-functional PNET, 6 patients (37.5%) had an insulinoma, and the remaining one patient had a gastrinoma. The mean age was 59.3±10.5 for pancreatic adenocarcinomas and 45.1±10.6 for PNETs. The mean age at diagnosis was significantly higher in patients with pancreatic adenocarcinomas than the patients with PNET (p<0.001). Preoperative mean hemoglobin levels were significantly lower in patients with pancreatic adenocarcinoma than those with PNET (12.4±1.8g/dl vs 13.7±2.2g/dl), (p<0.013). The preoperative median MPV levels were significantly lower in patients with PNET 7.8fL (7.2-9.4) than in patients with pancreatic adenocarcinomas 8.6fL (6.6-13.5), (p<0.014). In subgroup analysis, a significant difference in MPV levels was mainly caused by the difference between pancreatic adenocarcinomas and non-functional PNETs (p=0.017). The cut-off value of MPV level for detection of PNETs was calculated as≤7.8fL using ROC analysis [Sensitivity: 66.7%, specificity: 75.9%, AUC: 0.734 (0.587-0.880) p=0.022]. In logistic regression analysis, independent predictive factors for determining PNETs in the differential diagnosis of pancreatic adenocarcinomas were calculated as age (OR=0.068, 95% CI: 0.012-0.398), Ca 19-9 (OR=0.039, 95% CI: 0.006-0.263), MPV (OR=0.595, 95% CI: 0.243-1.458), and hemoglobin (OR=1.317, 95% CI: 0.831-2.086). CONCLUSION Age, Ca 19-9, MPV, and hemoglobin levels have diagnostic value for distinguishing PNETs from pancreatic adenocarcinomas.
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Affiliation(s)
- Kerem Karaman
- Department of Gastroenterological Surgery, Turkiye Yuksek Ihtisas Teaching and Research Hospital, Ankara, Turkey
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