Associations of sirtuins with clinicopathological parameters and prognosis in non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1-7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. METHODS: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. RESULTS: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adeno-carcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. CONCLUSION: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC.

Identification of Long Non-Coding RNAs for Predicting Prognosis Among Patients with Thymoma.

BACKGROUND: Thymoma is the most common primary anterior mediastinal neoplasm with a high recurrence rate. Long noncoding RNAs (lncRNAs) have recently been indicated to be used as diagnostic and prognostic indicators for different cancers. The aim of this study was to identify new tumor-specific prognostic lncRNA markers that can improve the treatment and follow-up of patients with thymomas. METHODS: One hundred seventeen thymoma patients with clinical information and level 3 RNAseqv2 data were downloaded from The Cancer Genome Atlas. Prognostic lncRNAs were identified using Kaplan-Meier survival analyses and univariate Cox proportional hazards regression analyses. A predictive risk scoring model was subsequently created using independently significant lncRNAs from a multivariate Cox regression analysis. RESULTS: Masaoka stage and 13 lncRNAs were significantly associated with RFS among 117 thymoma patients, while 59 lncRNAs were significantly associated with OS (all p < 0.05). Multivariate analyses revealed that OS was only independently associated with one lncRNA (JPX) and that RFS was only independently associated with three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1). A risk score model constructed by the three lncRNA expressions showed that the high-risk group was more likely to experience recurrence. CONCLUSIONS: The expression profile for three lncRNAs (AFAP1-AS1, LINC00324, and VLDLR-AS1) could be used to independently predict RFS among thymoma patients, which may be as prognostic biomarkers for thymoma.

Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell.

Lung cancer is recognized as the most prevalent type of cancer with high death rate. Ginsenoside Rg3 isolated from Traditional Chinese Medicine Panax Ginseng has significant anticancer effects on many tumors. In this study, the effects of ginsenoside Rg3 on cells viability, apoptosis and PI3K/Akt signaling pathway in lung cancer cells were investigated in vitro and in vivo. In vitro, the viability of lung cancer cell lines A549，H23 was examined by CCK-8 kits; The proportion of cell apoptosis was measured by flow cytometry. The expression of p-PI3K/PI3K and p-Akt/Akt was evaluated with Western blot. In vivo, A549，H23 cells were subcutaneously injected into the nude mice. Histopathological analysis was stained with HE, and TUNEL assay was used to detect cell apoptosis. The results showed that Rg3 obviously inhibited cell viability, induced apoptosis and inhibited PI3K/Akt signalling pathway on A549, H23 cells in vitro and in vivo. Rg3 effectively inhibited the volume and weight of tumor in xenografts model, which may be related with inhibiting PI3K/Akt signaling pathways.

Vitamin D status among infants, children, and adolescents in southeastern China.

OBJECTIVE: Vitamin D deficiency and insufficiency are global public health problems, which must first be identified before they can be appropriately addressed, and yet information is strikingly lacking in most parts of the Asia and Pacific region. The study aimed to document and account for the actual situation in Wenzhou on the southeastern coast of China. SUBJECTS AND METHODS: Serum 25-hydroxyvitamin D levels among a total of 5845 infants, preschool children, school children, and adolescents aged 1-18 years were examined between March 2014 and February 2015. RESULTS: Their mean levels were (110.2±26.8), (77.5±25.7), (55.6±15.4), and (47.2±13.9) nmol/L, respectively. Older age groups were involved in increasing risk of vitamin D deficiency and insufficiency. There were significant seasonal differences in its median level and prevalence of deficiency and insufficiency among school children and adolescents, but there was no significant sex difference in mean level and prevalence in any age group. CONCLUSIONS: Vitamin D deficiency and insufficiency were prevalent among infants, preschool children, school children, and adolescents in Wenzhou. A vitamin D-rich diet and outdoor activities for 1-2 h per day under the natural conditions favorable to its endogeous synthesis do not suffice. The vitamin D status in Wenzhounese infants excelling over that in the US was the result of its supplementation thanks to the Chinese Medical Association recommendations, which should be consequently extended to more age groups. Life style shaped by socio-economic environments affects vitamin D status. Knowledge on the importance of vitamin D for healthy growth should be popularized.

Relationship between HOMA-IR and serum vitamin D in Chinese children and adolescents.

BACKGROUND: The objective of this study was to examine the cross-sectional relationship between homeostasis model assessment for insulin resistance (HOMA-IR) and serum 25-hydroxyvitamin D (25-OHD) level in Chinese children and adolescents. METHODS: Anthropometric indices, lipid metabolic profile, and serum levels of glucose, insulin and 25-OHD were determined among 278 healthy prepubertal and pubertal, normal and overweight/obese children and adolescents aged 8-18 years between March 2014 and February 2015. RESULTS: HOMA-IR was significantly different across vitamin D statuses (p<0.001), even after adjusting for body mass index (BMI) (p=0.035) and waist-to-height ratio (p=0.044); the difference was not significant between the vitamin D deficient and insufficient groups (p=0.120). HOMA-IR negatively correlated with serum 25-OHD level for all subjects (R2=0.148, p<0.001). Furthermore, they negatively correlated in the normal (R2=0.160, p<0.001) and overweight/obese (R2=0.086, p<0.001) groups, respectively. The regression lines of the two groups were parallel (p=0.669) but had a significantly different intercept (p<0.001). An association between HOMA-IR and BMI and serum 25-OHD level (R2=0.654, p<0.001) was demonstrated based on the stepwise multiple linear regression analysis of age, sex, pubertal maturation, BMI, waist-to-height ratio, triglyceride, cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), 25-OHD and HOMA-IR. CONCLUSIONS: Our findings supported that lower vitamin D status is strongly associated with worse HOMA-IR.

[Relationship between hepatitis B virus DNA and hepatitis B virus large envelope protein].

OBJECTIVE: To investigate the relationship between HBV DNA and hepatitis B virus large envelope protein (HBV-LP) in patients with chronic hepatitis B. METHODS: Serum HBV DNA was detected by RT-PCR and the HBV-LP was detected by enzyme linked immunosorbent assay in 320 serum samples collected from patients with chronic hepatitis B. RESULTS: There were no significant difference between positive rate of HBV-LP and that of HBV DNA in different HBeAg patterns (P>0.05). Serum HBV-LP levels were closely correlated with HBV DNA copies (r=0.949). CONCLUSION: Serum HBV-LP is a reliable serological marker that can reflect the replication of HBV.

[Changes of serum leptin and vascular endothelial growth factor in children with congenital heart disease].

OBJECTIVE: To study the changes of serum leptin (LEP) and vascular endothelial growth factor (VEGF) in children with congenital heart disease(CHD) and their roles in CHD. METHODS: Forty-eight children with acyanotic CHD (ACHD group), 20 age-matched children with cyanotic CHD (CCHD group) and 20 healthy children (control group) were enrolled. The ACHD group was subdivided into two groups with (n=20) or without concurrent heart failure (n=28). Serum LEP, VEGF, total protein and albumin levels and body mass index (BMI) were measured. RESULTS: Serum total protein and albumin levels were not apparently different in all CHD children from healthy controls, but there was a significant difference in the BMI between them (p<0.01). Serum LEP and VEGF levels and the ratio of LEP/BMI in all CHD children were significantly higher than those in healthy controls (p<0.01). Compared with the ACHD group without heart failure, the serum LEP and VEGF levels and the ratio of LEP/BMI in the CCHD and the ACHD with heart failure groups increased significantly (p<0.01). In the ACHD group, serum LEP level was positively correlated with BMI (p<0.01). In the CCHD group, there were positive correlations between serum LEP level and serum VEGF level (p<0.01) and between hemoglobin concentration and serum VEGF level (p<0.01). Arterial oxygen saturation was negatively correlated with serum VEGF (p<0.01) and LEP levels (p<0.01) in the CCHD group. CONCLUSIONS: Both VEGF and LEP play roles in the pathophisiological process of CHD. VEGF and LEP are associated with the development of heart failure in children with ACHD.

Serum thymidine kinase 1 reflects the progression of pre-malignant and malignant tumors during therapy.

This study evaluated the clinical utility of serum thymidine kinase 1 (STK1) in following the progression of pre-malignancies and malignancies and in monitoring the response of common carcinomas to therapy within a routine clinical setting. The STK1 concentration levels of patients with malignancies (n=224), pre-malignancies (n=10), non-tumor/non-proliferating diseases (systemic lupus erythematosus, SLE) (n=53), benign tumors (n=20) and healthy volunteers (n=761) were determined by enhanced chemoluminescence dot blot assay. Prior to treatment, STK1 levels in the pre-malignant group alone (3.1±2.3) or in the pre-malignant and malignant groups together (2.3±1.9) were significantly higher than in the benign (1.4±0.8), SLE (1.1±0.8) or healthy volunteer (0.6±0.4) groups (p<0.01). According to ROC analysis, the STK1 assay provided a high degree of discrimination between STK1-positive pre-malignant (0.978) or pre-malignant + malignant (0.941) patients and STK1-negative healthy individuals. After varying treatments (surgery, chemotherapy, X-ray), STK1 levels increased by 40-50% during the first month, then decreased back to normal values or even lower. Following treatment, STK1 levels were significantly increased in squamous cell carcinoma (SCC) as compared to adenocarcinoma (AC) patients. In other types of malignancies, STK1 levels decreased from as early as the first month. The STK1 levels of relapsed treated patients were significantly higher (50-60%) than those of mid/long-term treated patients. In conclusion, the STK1 assay discriminated between patients with malignancies and healthy individuals very well, and is therefore potentially useful for a broad range of clinical applications. For example, it could be used for the evaluation of early tumor progression or of tumor progression during therapy in routine clinical settings, as well as for the screening of healthy individuals.