Risk factors for development of melanoma brain metastasis and disease progression

AbstractObjectivesIn December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19.MethodsIn this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy.ResultsThe data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954–10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097–0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111–0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746–0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients.ConclusionsWe designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

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O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

British Journal of Surgery ◽

10.1093/bjs/znab117.028 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

S Keelan ◽

S Charmsaz ◽

S Purcell ◽

D Varešlija ◽

S Cocchiglia ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastasis ◽

Disease Progression ◽

Therapeutic Target ◽

Disease Free Survival ◽

Metastatic Breast ◽

Potential Therapeutic Target ◽

Rna Methylation ◽

Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain. Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

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Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

BioMed Research International ◽

10.1155/2017/8076384 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Wei Wang ◽

Chao Bian ◽

Di Xia ◽

Jin-Xi He ◽

Ping Hai ◽

...

Keyword(s):

Risk Factors ◽

Brain Metastasis ◽

Lung Adenocarcinoma ◽

Carcinoembryonic Antigen ◽

Roc Curve ◽

Univariate Analysis ◽

Significant Risk ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Increased Risk

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

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P146 Disease progression in del (5q) MDS patients treated with lenalidomide: analysis of risk factors and long-term outcome in 44 patients

Leukemia Research ◽

10.1016/s0145-2126(07)70216-3 ◽

2007 ◽

Vol 31 ◽

pp. S120-S121

Author(s):

A.A.N. Giagounidis ◽

S. Haase ◽

V. Lohrbacher ◽

M. Heinsch ◽

B. Schuran ◽

...

Keyword(s):

Risk Factors ◽

Disease Progression ◽

Term Outcome ◽

Long Term Outcome

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Low incidence of melanoma brain metastasis in the hippocampus

Radiotherapy and Oncology ◽

10.1016/j.radonc.2014.01.012 ◽

2014 ◽

Vol 111 (1) ◽

pp. 59-62 ◽

Cited By ~ 25

Author(s):

Angela M. Hong ◽

Chao Suo ◽

Michael Valenzuela ◽

Lauren E. Haydu ◽

Kari D. Jacobsen ◽

...

Keyword(s):

Brain Metastasis ◽

Melanoma Brain Metastasis ◽

Low Incidence

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Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells

Cancers ◽

10.3390/cancers13051049 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1049

Author(s):

Thuy T. Tran ◽

Chetan K. Rane ◽

Christopher R. Zito ◽

Sarah A. Weiss ◽

Shlomit Jessel ◽

...

Keyword(s):

Tumor Microenvironment ◽

Brain Metastasis ◽

Immune Cell ◽

Tissue Microarrays ◽

Pleckstrin Homology Domain ◽

Neoplastic Progression ◽

Melanoma Brain Metastasis ◽

Pdcd4 Expression ◽

Programmed Cell Death 4 ◽

And Function

Little is known about the subcellular localization and function of programmed cell death 4 (PDCD4) in melanoma. Our past studies suggest PDCD4 interacts with Pleckstrin Homology Domain Containing A5 (PLEKHA5) to influence melanoma brain metastasis outcomes, as high intracranial PDCD4 expression leads to improved survival. We aimed to define the subcellular distribution of PDCD4 in melanoma and in the tumor microenvironment during neoplastic progression and its impact on clinical outcomes. We analyzed multiple tissue microarrays with well-annotated clinicopathological variables using quantitative immunofluorescence and evaluated single-cell RNA-sequencing on a brain metastasis sample to characterize PDCD4+ immune cell subsets. We demonstrate differences in PDCD4 expression during neoplastic progression, with high tumor and stromal PDCD4 levels associated with improved survival in primary melanomas and in intracranial metastases, but not in extracranial metastatic disease. While the expression of PDCD4 is well-documented on CD8+ T cells and natural killer cells, we show that it is also found on B cells and mast cells. PDCD4 expression in the tumor microenvironment is associated with increased immune cell infiltration. Further studies are needed to define the interaction of PDCD4 and PLEKHA5 and to evaluate the utility of this pathway as a therapeutic target in melanoma brain metastasis.

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Gait Risk Factors for Disease Progression Differ Between Non-traumatic and Post-traumatic Knee Osteoarthritis

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2021.07.014 ◽

2021 ◽

Author(s):

Shawn M. Robbins ◽

Jean-Pierre Pelletier ◽

François Abram ◽

Mathieu Boily ◽

John Antoniou ◽

...

Keyword(s):

Risk Factors ◽

Knee Osteoarthritis ◽

Disease Progression ◽

Post Traumatic

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