[Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma].

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

[Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) in differential diagnosis of benign and malignant cutaneous melanocytic lesions. Methods: Fifty-nine cases of melanoma (50 cases of skin primary melanoma, and 9 cases of metastatic melanoma) and 48 cases of melanocytic nevus (40 cases of common nevus and 8 cases of dysplastic nevus) were subject to PRAME immunohistochemistry staining.The difference of PRAME expression between melanoma and melanocytic nevus was analyzed. Results: Among the 50 patients with primary cutaneous melanoma, there were 23 males and 27 females ranging in age from 33 to 87 years (average age 62.4 years, median age 64.5 years). Among the 9 metastatic melanoma there were 7 males and 2 females ranging in age from 40 to 82 years (average age 64 years, median age 65 years). Twenty-six cases (26/50, 52.0%) of cutaneous primary melanoma and 4 cases (4/9) of metastatic melanoma showed diffuse positive PRAME staining. 40 cases (40/40, 100%) of common nevus and 8 (8/8) cases of dysplastic nevus were PRAME negative. Compared with melanocytic nevus group, the melanoma group included more cases with diffuse positive PRAME staining (P<0.05). The sensitivity and specificity of using PRAME to differentiate primary cutaneous melanoma from melanocytic nevus in the cohort is 52.0% and 100%. Conclusions: There is a significant difference in the expression of PRAME between melanoma and melanocytic nevus.Thus, PRAME can be used as an auxiliary diagnostic tool for differentiating benign from malignant cutaneous lesions.

[Suggestions on the nomenclature of liver cancer].

Currently, the systematized nomenclature of medicine (SNOMED) of liver cancer is confusing, and it is mixed with the SNOMED of cholangiocarcinoma. We hereby presented our own points, hoping to provide a reference for standardizing the nomenclatures and classifications of liver cancer in future clinical studies. The preface of Chinese Guidelines of Primary Liver Cancer Diagnosis and Treatment (2019 Edition) indicated that primary liver cancer mainly includes three different pathological types, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and mixed-type carcinoma of both HCC and ICC. These three types of carcinoma show great differences in terms of pathogenesis, biological behavior, histological morphology, treatment methods, and prognosis, among which, HCC accounts for 85% to 90%. Therefore, this study is a detailed analysis of the above-mentioned related SNOMED and proposes suggestions for corrections.

Hepatocellular carcinoma progression is protected by miRNA-34c-5p by regulating FAM83A.

OBJECTIVE: To elucidate the role of microRNA-34c-5p (miRNA-34c-5p) in the progression of hepatocellular carcinoma (HCC) and the indicated mechanism. PATIENTS AND METHODS: Relative levels of miRNA-34c-5p and FAM83A in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Their influences on clinical features in HCC patients were analyzed. Kaplan-Meier method was introduced for assessing the relationship between miRNA-34c-5p and overall survival in HCC. After overexpression of miRNA-34c-5p in HepG2 and HB611 cells, we detected proliferative, migratory and invasive abilities by cell counting kit-8 (CCK-8) and transwell assay. The interaction between miRNA-34c-5p and FAM83A was explored by Dual-Luciferase reporter assay. Finally, their co-regulation on HCC cell phenotypes was examined. RESULTS: MiRNA-34c-5p was downregulated in HCC tissues, especially stage III+IV cases. Its level was correlated to tumor size, tumor number and TNM staging in HCC. Overexpression of miRNA-34c-5p inhibited proliferative, migratory and invasive abilities in HepG2 and HB611 cells. In addition, miRNA-34c-5p targeted on FAM83A and negatively regulated its level. Overexpression of FAM83A could reverse the inhibitory effects of miRNA-34c-5p on malignant phenotypes of HCC cells. CONCLUSIONS: By negatively regulating FAM83A level, miRNA-34c-5p alleviates the progression of HCC.

Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment.

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2×10^{-4}≲|Δm_{41}^{2}|≲0.3 eV^{2} mass range. The resulting limits on sin^{2}2θ_{14} are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δm_{41}^{2}|≲0.2 eV^{2} region.

Using multiple cytokines to predict hepatocellular carcinoma recurrence in two patient cohorts.

BACKGROUND: Cytokines are tightly linked to the carcinogenesis, development and prognosis of hepatocellular carcinoma (HCC). We determined the prognostic value of 39 circulating cytokines in HCC patients after radical resection and then developed a novel cytokine-based prognostic classifier (CBPC) for the prediction of patient prognosis. METHODS: A total of 179 patients were divided into two cohorts based on the date of radical resection. Thirty-nine cytokines were simultaneously analysed in patient serum samples using multiplex bead-based Luminex technology. Support vector machine-based methods and Cox proportional hazard models were used to develop a CBPC from the training cohort, which was then validated in the validation cohort. RESULTS: Among seven cytokines significantly correlating with the disease-free survival (DFS) in the training cohort, six of them were validated to be significant prognostic factors to predict DFS and overall survival (OS) in the validation cohort, namely fibroblast growth factor 2 (FGF-2), growth-regulated oncogene (GRO), interleukin 8 (IL-8), interferon gamma-induced protein 10 (IP-10), vascular endothelial growth factor (VEGF), and interferon alpha-2 (IFN-α2). By integrating six cytokines and three clinical characteristics, we developed a CBPC to predict the recurrence and 3-year OS of HCC patients (sensitivity, 0.648; specificity, 0.918). In the validation cohort, the CBPC were confirmed to have significant predictive power for predicting tumour recurrence and OS (sensitivity, 0.585; specificity, 0.857). Interestingly, IFN-α2 was the only cytokine being independent prognostic factor in both patient cohorts. CONCLUSION: Our study verifies the presence of specific cytokine-phenotype associations with patient prognosis in HCC. The CBPC developed include multiple circulating cytokines and may serve as a novel screening approach for identifying HCC patients with a high risk of post-resection recurrence and shorter OS. These individuals may also be suitable for cytokine-targeted therapies.

Risk assessment and distribution of soil Pb in Guangdong, China.

In this study, the spatial distributions of soil lead (Pb) concentration in three horizontal soils in Guangdong, China, were surveyed and analyzed using geostatistics and geography information systems (GIS). Findings indicated that the Pb geometric mean concentration of 23.3 mg/kg in surface soils was found to be higher than those in global soils, which ranged from 2.3-235 mg/kg. In addition, the Pb geometric mean concentrations from A- to C-horizon were found to be 23.3, 27.2, and 28.6 mg/kg, respectively. The classification of a soil Pb environmental risk in an area was likewise presented based on the different levels of environmental quality of Pb and was done by GIS technology. Accordingly, there is a higher local concentration of Pb in the surrounding areas of Guangzhou where there is higher population density and in the north of Guangdong, which is a historic mining area. The results obtained by the environmental risk assessment reveal that about 46% of total surveyed area was above the background value, that is, 2.7% of the total area was at risk of pollution.