Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.

Background: Uveal melanoma (UM) is an aggressive primary intraocular tumor in adults, with high metastatic capacity and high morbidity. However, the mechanisms of UM metastasis have not been clearly elucidated.Methods: The PTK2 expression and activation were performed in the Cancer Genome Atlas (TCGA) database and 25 patients of UM. The role of PTK2 in promoting metastasis was explored in vitro and in vivo. Subsequently, we revealed the correlation between PTK2 expression and epithelial-to-mesenchymal transition (EMT). Finally, we explored the reason for the high expression of PTK2 in UM.Results: Our study found that protein tyrosine kinase 2 (PTK2) was overexpressed in UM specimens, and as a novel independent risk factor, its overexpression predicted the poor survival of UM patients. For the molecular mechanism, PTK2 promoted EMT phenotype, thus leading to tumor metastasis in UM cells. Subsequently, we have demonstrated that PTK2 was a functional gene of chromosome 8q gain accounting for UM metastasis, providing a novel molecular mechanism for the aberrantly expression and activation of PTK2 in UM.Conclusion: Our data reveal the important role and mechanism of PTK2 in the metastatic process of UM, which may clue to a new predictive biomarker for UM metastasis and a new therapeutic target for UM treatment.

Background and purpose: Coronavirus disease 2019 (COVID-19) was spreading all over the world. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) primarily invades and infects the lungs of humans leading to COVID-19. Mild to severe clinical symptoms such as fever, cough, and shortness of breath were existed in those patients. One of the most common changes in these patients was abnormal blood routine. However, uncertainty remains regarding the dynamic characteristics of platelet in COVID-19 patients due to limited data. Therefore, we aimed to analyze the association between dynamic characteristics of blood platelet and disease severity, and to identify new monitoring indicators to treat the COVID-19 patients. Methods: In this cohort study, 398 COVID-19 patients treated in the Shenzhen Third People’s hospital from December 16, 2019 to March 26, 2020 were collected and participated. All data of participants including the clinical characteristics, imaging and laboratory information were collected. All patients included in our study were classified as four groups (mild, common, severe, and critical types) regarding clinical symptoms and relevant severe failures based on the Diagnosis Criteria. Platelet count was examined at the baseline and every 3–5 days during hospitalization. Results: The platelet count varied with clinical classifications. The platelet count in mild type was normal without significant fluctuation. While the blood platelet count of most common and severe patients had obvious fluctuations, showing as a dynamic change that first rose and then fell to the level at admission, which was consistent with the trend of lung inflammation. Bone marrow smears further showed that bone marrow hyperplasia was normal in mild, common and severe type patients, and megakaryocytes and their platelet-producing functions were not abnormal. Conclusions: Our results suggested that the dynamic changes of platelet count might be a predictor of lung inflammation alteration for COVID-19 patients. The changes in platelet count might be a responsive pattern secondary to lung inflammation. The function of bone marrow may be slightly affected by SARS-CoV-2 infection.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. More than half of UM cases develop distant metastasis to the liver, lung, bone, and other organs, which frequently results in patient death. However, the mechanisms underlying UM metastasis remain largely unknown. Here, we report that protein tyrosine kinase 2 (PTK2), a nonreceptor protein tyrosine kinase also known as focal adhesion kinase (FAK), was overexpressed in most examined UM specimens. Furthermore, we identified PTK2 expression as a novel independent risk factor that predicts poor prognosis of UM patients. Mechanistic studies revealed that PTK2 promotes the EMT phenotype, leading to metastasis of UM cells. We showed that PTK2, located on chromosome 8q, is a functional gene of chromosome 8q gain to UM metastasis, which may represent the molecular mechanism for the aberrant expression and activation of PTK2 in UM. Our data reveal a novel role and mechanism of PTK2 in the metastatic process of UM, suggesting PTK2 may be a potential prognostic biomarker for UM metastasis and a promising therapeutic target for UM treatment.