Τετάρτη 15 Δεκεμβρίου 2021

Identification of heterogeneity and prognostic key genes associated with uveal melanoma using single-cell RNA-sequencing technology

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Uveal melanoma (UM) is the most common intraocular malignancy in adults. The prognosis is poor once metastasis has developed. The treatment of metastatic UM remains challenging nowadays due to lacking a deep understanding of the biological characteristics of this disease. Here, we revealed the cell subpopulations w ith distinct functional status and the existence of cells with high invasive potential within heterogeneous primary and metastatic UM. The single-cell sequencing data were retrieved from GSE139829 and GSE138433, through which we identified a new cell cluster related to metastatic UM as a unique type of immune cell. The cell–cell communication was conducted by 'Cellchat' to understand the cell crosstalk between these immune cells and their surrounding cells. The crucial signals contributing most to outgoing or incoming signaling of this cell group were identified to reveal the crucial pathway genes. Furthermore, we judged the prognostic value of these candidates on the basis of the data downloaded from The Cancer Genome Atlas. The results demonstrated that the increased IL10, SELPLG, EPHB and ITGB2 signaling pathways could be promising predicting factors for the patient prognosis in UM. Conclusively, we discover the potential key signals of UM for occurrence and metastasis, and also provide a theoretical basis for judging whether there is a high risk of metastasis or recurrence. * Songlin Sun and Rui Shi contributed equally to the writing of this article. Received 25 May 2021 Accepted 24 August 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Fengyuan Sun, PhD, MD, Tianjin Medical University Eye Hospital, Xiqing District, No.251 Fukang Road, Tianjin 300384, Tianjin, China, Tel: +086 022 86428810; e-mail: tianjiny2020@163.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Thyroid Cancer Incidence Trends

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Objective

To analyze thyroid cancer incidence trends among Filipinos relative to non-Filipino Asians and non-Hispanic Whites in the US.

Study Design

Population-based analysis of cancer incidence data.

Methods

Population-based analysis of cancer incidence data from Surveillance, Epidemiology, and End Results 9 detailed Asian/Pacific Islander subgroup incidence and population datasets. Adult patients aged 20 and older with thyroid cancer diagnosed in 2004 to 2014 were included. Annual percent change (APC) of the incidence rates were calculated using joinpoint regression analysis.

Results

The incidence rates were 19.57 (95% CI 19.03–20.12) per 100,000 for Filipinos, 10.45 (95% CI 10.22–10.68) per 100,000 for non-Filipino Asians, and 13.94 (95% CI 13.85–14.02) per 100,000 for non-Hispanic Whites. The highest increase was seen among non-Hispanic Whites (average APC 5.04, 95% CI 4.61–5.46). Incidence rates of tumors ≤ 2 cm remained stable among Filipinos but increased in non-Filipino Asians (average APC 5.38, 95% CI 2.51–8.34) and non-Hispanic Whites (average APC 5.81 95% CI 4.52–7.11).

Conclusion

Filipinos have high incidence of thyroid cancer compared with other racial/ethnic groups. However, non-Hispanic Whites have the highest increase in incidence rates, resulting in a significant narrowing of the gap in incidence rates between Filipinos and non-Hispanic Whites. This is most likely due to enhanced detection of small tumors in non-Hispanic Whites. Laryngoscope, 2021

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Concomitant Variants in NF1, LZTR1, and GNAZ Genes Probably Contribute to the Aggressiveness of Plexiform Neurofibroma and Warrant Treatment with MEK Inhibitor

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Abstract

Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. Here, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two Rasopathy-associated genes were identified using whole exome sequencing - a de-novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G Protein Coupled Receptor. Cells expressing mutant GNAZ exhibited increased ERK 1,2 activation compared to those expressing wild type GNAZ. Taken together, we suggest the variants in NF1, LZRT1, and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.

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