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Nasopharyngeal carcinoma (NPC), a malignant tumor at the top and side of the nasopharyngeal cavity, highly occurs in the southern region of China. Cancer cell metastasis is one of the leading causes of death in NPC patients. Osteopontin (OPN), is a phosphorylated extracellular matrix protein with a variety of functions, was found to be overexpressed in many cancers. However, the expression and role of OPN in patients with NPC in Guangxi, China are unclear. Here, we observed that NPC patients had upregulated OPN at mRNA protein and levels. Immunochemistry (IHC) analysis of OPN expression in 68 NPC clinical specimens indicated that high expression of OPN had positive correlation with NPC lymph node metastasis (P = 0.012), distant metastasis (P = 0.001) and TNM staging (P = 0.018). Moreover, compared with relatively low OPN, NPC patients with higher expression of OPN showed a poorer overall survival rate (P = 0.001, log rank test). Multivariate analysis showed that OPN expression in NPC was an independent prognostic marker. The proliferation, apoptosis and migration ability of CEN-2Z cancer cells in NPC were determined by MTT, flow cytometry and wound-healing assays, respectively. Upregulation of OPN in CEN-2Z cancer cells promoted cancer cell proliferation and migration, and suppressed apoptosis. In sum, our result suggests OPN could be used as a valuable oncoprotein and show that overexpression of OPN in NPC may serve as a potential prognostic marker. [ABSTRACT FROM AUTHOR]

Background and purpose: The prognostic nutrition index (PNI) has been associated with the prognosis of various medical disorders. This study aimed to explore the correlation between PNI and the long-term outcomes of adult patients afflicted with moyamoya disease (MMD). Methods: This prospective study initially employed 138 adult patients diagnosed with MMD. After excluding 15 patients who did not meet the criteria, a total of 123 patients were included. Participants were divided into three groups based on the tertile of change in the PNI score. Statistical analysis compared clinical information and lab tests among the groups. The study was conducted between July 1 and December 31, 2019. Results: After adjusting for multiple variables, patients in the upper two tertiles (tertiles 2–3) exhibited a significantly lower risk of adverse long-term outcomes compared to those in the lowest tertile (tertile 1) (OR, 0.089; 95% CI, 0.009–0.895; P = 0.040). Furthermore, adding PNI tertile to traditional risk factors substantially improved predicting adverse long-term outcomes (net reclassification improvement: 98.03%, P = 0.000; integrated discrimination improvement: 4.65%, P = 0.030). However, there was no statistically significant difference between the first PNI tertile (tertile 1) and the upper two tertiles (tertiles 2–3) in the Kaplan–Meier curve of stroke incidence (log-rank test, P = 0.244). Conclusions: A higher PNI level was significantly associated with a reduced risk of unfavorable long-term outcomes. Nevertheless, the PNI score did not predict stroke recurrence during extended follow-up. This study provides insights into a potential predictor of adverse long-term outcomes after revascularization in MMD patients. Registration number: ChiCTR2000031412 [ABSTRACT FROM AUTHOR]

Background: Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations. Methods: Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort. Results: A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively). Conclusion: This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC. [ABSTRACT FROM AUTHOR]

Objectives: To explore the correlations of parameters derived from standard diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) with the Ki-67 proliferation status.Methods: Seventy-five patients with histologically proven sinonasal malignancies who underwent standard DWI, DKI and IVIM were retrospectively reviewed. The mean, minimum, maximum and whole standard DWI [apparent diffusion coefficient (ADC)], DKI [diffusion kurtosis (K) and diffusion coefficient (Dk)] and IVIM [pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f)] parameters were measured and correlated with the Ki-67 labelling index (LI). The Ki-67 LI was categorised as high (> 50%) or low (≤ 50%).Results: The K and f values were positively correlated with the Ki-67 LI (rho = 0.295~0.532), whereas the ADC, Dk and D values were negatively correlated with the Ki-67 LI (rho = -0.443~-0.277). The ADC, Dk and D values were lower, whereas the K value was higher in sinonasal malignancies with a high Ki-67 LI than in those in a low Ki-67 LI (all p < 0.05). A higher maximum K value (Kmax > 0.977) independently predicted a high Ki-67 status [odds ratio (OR) = 7.614; 95% confidence interval (CI) = 2.197-38.674; p = 0.017].Conclusion: ADC, Dk, K, D and f are correlated with Ki-67 LI. Kmax is the strongest independent factor for predicting Ki-67 status.Key Points: • DWI-derived parameters from different models are capable of providing different pathophysiological information. • DWI, DKI and IVIM parameters are associated with Ki-67 proliferation status. • K max derived from DKI is the strongest independent factor for the prediction of Ki-67 proliferation status. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are a class of small non-coding RNAs, approximately 21-25 nucleotides in length. Recently, some researchers have demonstrated that plasma miRNAs are sensitive and specific biomarkers of various cancers. Using quantitative real-time PCR, the expression levels of miR-454-3p were compared between pre-operative plasmas from 70 glioma patients and 70 healthy controls, and between these pre-operative and post-operative plasmas. Kaplan-Meier analysis was used to evaluate the association of miR-454-3p with prognosis of glioma patients. The expression levels of miR-454-3p in plasma in glioma patients were significantly higher than that from healthy controls. The expression levels of miR-454-3p were higher in high grade gliomas than in low grade gliomas. The AUC of the expression of miR-454-3p in plasma for glioma diagnosis was 0.9063. The expression levels of miR-454-3p in the post-operative plasmas were significantly downregulated when compared to the pre-operative plasmas. Moreover, the prognosis of glioma with high miR-454-3p expression was significantly worse compared with that of glioma with low miR-454-3p expression. Our results suggested that plasma miR-454-3p could be a novel potential diagnostic biomarker for glioma. [ABSTRACT FROM AUTHOR]

Purpose: Downregulation of miRNA expression has been identified as a novel feature of renal cell carcinoma (RCC). Recently, miR-129-2 is well known to be frequently reduced by DNA methylation and has anti-tumor effects in various tumors but so far not in RCC. The aim of this study was to investigate the clinical significance and the role of it in RCC. Methods: The expression levels of miR-129-3p and miR-129-5p, two mature products of miR-129-2, were determined by real-time quantitative reverse transcription PCR in 69 cases of paired different kidney tumors and normal tissues and clear cell RCC (ccRCC) cell lines. The roles of them in RCC cells were assessed by functional analyses. Protein expression was detected by Western blot. Results: miR-129-3p, but not miR-129-5p, was widely attenuated in human ccRCC, and chromophobe RCC. miR-129-3p could yield 73.5 % accuracy in discriminating ccRCCs from normal tissues. The relative miR-129-3p expression significantly differed between malignant and benign kidney tumors. Importantly, low miR-129-3p levels were associated with short disease-free and overall survival. Ectopic expression of miR-129-3p robustly impaired RCC cell migratory and invasive properties, but had no impact on cell viability and cell cycle distribution. Finally, miR-129-3p decreased multiple metastasis-related genes in RCC cells, including SOX4, phosphorylation of focal adhesion kinase and MMP-2/9 expression. Conclusions: miR-129-3p may act as a promising diagnostic biomarker for discriminating ccRCC from benign tumors and normal tissues and an independent prognostic biomarker in ccRCC. miR-129-3p may exert its anti-metastatic function through modulating multiple targets. [ABSTRACT FROM AUTHOR]

Purpose: Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers, but the expression patterns of the enzymes responsible for generating miRNAs remain largely unexplored. In this study, we investigated the expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, which were closely correlated with nasopharyngeal carcinoma (NPC) and patient survival. Methods: Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) using 24 NPC tissues, 7 normal nasopharyngeal epithelium samples (NPE) and NPC cell lines. In addition, protein levels were detected by immunohistochemistry (IHC) using an NPC tissue microarray (TMA), which include 251 NPC and 105 NPE cases. For some NPC patients can not be contacted, the survival data were available only for 146 patients. Kaplan-Meier analysis was performed, and the chi-square and log-rank tests were used to detect significance levels using SPSS 15.0 software. Results: The mean level of Dicer and Drosha mRNA were significantly down-regulated in NPC tissue specimens and cell lines when compared with controls. The low levels of Dicer and Drosha protein were frequently seen in NPC, and the low expression of Dicer and Drosha protein was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) of NPC patients. Conclusions: We observed that Drosha and Dicer expression was dysregulation in NPC compared with healthy control samples and was significantly correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise that the expression levels of Dicer and Drosha could be used as potential prognostic biomarkers for NPC. [ABSTRACT FROM AUTHOR]