Significance of plasma hepatocyte growth factor in diagnosis of benign and malignant solitary pulmonary nodules

Purpose: We aimed to figure out the difference of serum hepatocyte growth factor (S-HGF) level between benign and malignant solitary pulmonary nodules (SPNs) patients. Methods: The study comprised 42 serum samples from SPNs patients and 10 serum samples of healthy donors. The HGF level was measured by the commercially enzyme-linked immunosorbent assay (ELISA) kit. Results: By statistical analysis, the S-HGF levels of the malignant SPNs patients were significantly higher than that of control group (P < 0.05). Moreover, the levels of S-HGF in malignant group were also significantly higher than that in benign group (P < 0.05), while there was no significant difference between the benign and control group (P > 0.05). The levels of S-HGF were also shown no statistically significant difference (P > 0.05) in different pathologic types of lung cancer patients. In addition, the incidence of malignant SPNs increased when the S-HGF level ≥ 250 pg/ml. Conclusion: The detection of S-HGF level may be a new detection method used for the rapid diagnosis of benign and malignant SPNs.     

High prevalence of occult paragangliomas in asymptomatic carriers of SDHD and SDHB gene mutations

Hereditary paraganglioma is a benign tumor syndrome with an age-dependent penetrance. Carriers of germline mutations in the SDHB or SDHD genes may develop parasympathetic paragangliomas in the head and neck region or sympathetic catecholamine-secreting abdominal and thoracic paragangliomas (pheochromocytomas). In this study, we aimed to establish paraganglioma risk in 101 asymptomatic germline mutation carriers and evaluate the results of our surveillance regimen. Asymptomatic carriers of an SDHD or SDHB mutation were included once disease status was established by MRI diagnosis. Clinical surveillance revealed a head and neck paraganglioma in 28 of the 47 (59.6%) asymptomatic SDHD mutation carriers. Risk of tumor development was significantly lower in SDHB mutation carriers: 2/17 (11.8%, P=0.001). Sympathetic paragangliomas were encountered in two SDHD mutation carriers and in one SDHB mutation carrier. In conclusion, asymptomatic carriers of an SDHD mutation are at a high risk for occult parasympathetic paraganglioma. SDHB carrier risk is considerably lower, consistent with lower penetrance of SDHB mutations. For both syndromes, the risk of symptomless sympathetic paragangliomas is small.     

Clinical significance of joint detection of serum CEA,SCCA, and bFGF in the diagnosis of lung cancer

Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction.     

Down-regulation of microRNA152 is associated with the diagnosis and prognosis of patients with osteosarcoma

Potential values of microRNA152 (miR-152) as a serum diagnostic and prognostic biomarker have not been determined in human osteosarcoma. By detecting the expression of miR-152 among 80 osteosarcoma patients, 20 periostitis patients and 20 healthy individuals using qRT-PCR, we aimed to explore the clinical significance of miR-152 in osteosarcoma patients. The expression of miR-152 was significantly decreased in patients with osteosarcoma compared to patients with periostitis (P<0.01) and healthy controls (P<0.01). The relationship between clinicopathologic characteristics and miR-152 was analyzed by chi-square test. The outcome indicated that miR-152 might be linked with the development of osteosarcoma. Moreover, the receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of miR-152. The result demonstrated that miR-152 might be a promising diagnostic marker of osteosarcoma with an AUC of 0.956, combing with 92.5% specificity and 96.2% sensitivity. The relationship between miR-152 and overall survival of osteosarcoma patients was analyzed by Kaplan-Meier curve and log rank test. As a result, the survival time of patients with low miR-152 expression was significantly shorter than those with high miR-152 expression (P<0.001). Then Cox regression analysis was used to estimate the prognostic value of miR-152 in osteosarcoma. The outcomes showed that low miR-152 expression (P=0.004) might be a potential independent prognostic marker for osteosarcoma patients. These findings suggested that down-regulation of miR-152 could be considered as a predictor for diagnosis and prognosis of osteosarcoma patients.     

Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan

The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n = 28) were more resistant to reinfection (Fisher's exact test, P < 0.05) than newly recruited canal cleaners (n = 17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (χ² = 19.1, P < 0.0001), significantly larger portal vein diameter (P < 0.05) and enlarged spleen (χ² = 4.2, P < 0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P < 0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P < 0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P < 0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P < 0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P < 0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed.     

The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study

Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer.Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8.Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively)Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.     

miR-144 regulates transforming growth factor-β1 iduced hepatic stellate cell activation in human fibrotic liver

Objectives: Activation of hepatic stellate cells (HSCs) into collagen producing myofibroblasts is critical for pathogenesis of liver fibrosis. Transforming growth factor-β1 (TGF-β1) is one of the main profibrogenic mediators for HSC transdifferentiation. Recent studies have shown effect of microRNAs (miRNAs) on regulating TGF-β1-induced HSC activation during liver fibrosis. Here, we aimed to explore the roles of miR-144 and miR-200c in human liver fibrosis. Methods: Expression of TGF-β1 was detected in 42 fibrotic and 18 normal human liver tissues by quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry, and its correlation with α-smooth muscle actin (α-SMA) was calculated. miR-144 and miR-200c expression level in fibrotic liver tissues were also detected by qRT-PCR. The correlation of TGF-β1 expression with miR-200c and miR-144 in the fibrotic liver was analyzed. Results: The results showed that TGF-β1 expression was much higher in fibrotic liver than that in normal liver tissues (P<0.05). TGF-β1 protein high expressing liver fibrosis showed α-SMA positive cells in the liver parenchyma indicating activated HSCs. Expression of TGF-β1 in fibrotic liver was significantly correlated with α-SMA expression (R=0.633, P<0.001). Furthermore, miR-144 was less expressed in liver fibrosis (P<0.05) and was significantly correlated with expression of TGF-β1 in fibrotic liver tissues (R=-0.442, P<0.01). However, miR-200c did not show significant difference between normal and fibrotic liver (P=0.48) and correlation with TGF-β1 expression (R=0.106, P=0.51). Conclusion: All the results indicate that miR-144 can be a novel regulator of TGF-β1-induced HSC activation during liver fibrosis.     

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival

Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.     

Influence of protein kinase C (PKC) on the prognosis of diabetic nephropathy patients

Aims: To investigate the association between protein kinase C (PKC) and the prognosis of patients with diabetic nephropathy (DN). Methods: 92 patients with DN who had received treatments with angiotensin converting enzyme inhibitor (ACEI) or angiotensin-receptor blockade (ARB) were collected. The clinicopathologic characteristics were recorded and a 4-year follow-up with the final result of impaired renal functions (eGFR < 40 mL/min) was conducted. The expression of PKC was detected by immunohistochemical assay. Kaplan-Meier and Cox regression analysis were performed to estimate the effects of PKC on DN prognosis. Results: According to immunohistochemical analysis, there were 54 cases with positive expression of PKC (positive rate 58.7%). Meanwhile, during the follow-up, the urine protein, mean serum creatinine and eGFR in patients with positive PKC were all higher than those in negative expression group (P < 0.05). The expression of PKC was influenced by age (P < 0.001), course of disease (P < 0.001), blood pressure (P = 0.002), blood glucose (P < 0.001), HbA1c (P = 0.002), renal functions of patients before (P = 0.011) and after (P = 0.041) the biopsy. Besides, the Kaplan-Meier curve revealed that patients with positive PKC expression had shorter survival time than those with negative PKC expression (P < 0.001). Cox regression analysis indicated that HbA1c (P = 0.009), renal functions of patients after the biopsy (P = 0.002) and PKC (P = 0.028) were important factors in the prognosis of DN and they might be independent prognostic markers. Conclusion: The expression of PKC is relatively higher in DN patients than in healthy controls. And PKC may be a valuable prognostic marker for patients with DN.     

P15, MDM2, NF-κB,and Bcl-2 expression in primary bone tumor and correlation with tumor formation and metastasis

Primary bone tumor is one of the most common malignant tumors in skeletal system. It seriously affected bone movement and development with unclear pathogenesis. In this paper, rabbit VX-2 malignant bone tumor model was applied to explore apoptotic genes P15, MDM2, NF-κB and Bcl-2 correlation with primary bone tumor occurrence and metastasis. 0.3 ml rabbit VX-2 tumor cell suspension (1×10⁶/ml) was injected to the marrow cavity of the right tibia condyle to establish the rabbit malignant bone tumor model, while equal amount of the saline was injected to the left tibia as control. Real-time PCR was applied to determine P15, MDM2, NF-κB and Bcl-2 expression level. Immunohistochemistry was performed to detect the abovementioned genes expression in lung, stomach, kidney and bladder. Compared with control, P15 expression level in the inoculation site surrounding tissues decreased obviously following the inoculate time elongation (P<0.05), while Bcl-2, MDM2 and NF-κB expression significantly increased (P<0.05). Bcl-2 showed significant correlation with MDM2 and NF-κB (P<0.05). At the 2, 4, 6 weeks, Bcl-2, MDM2 and NF-κB in lung, Bcl-2 in kidney, and Bcl-2 and MDM2 in bladder positively expressed (P<0.05), whereas P15 gene exhibited no significant positive expression in these tissues (P>0.05). P15, MDM2, NF-κB, and Bcl-2 genes expression levels can effectively reflect malignant bone tumor growth of rabbit tibia. MDM2, NF-κB and Bcl-2 genes involved in primary bone tumors metastasis directly. It has important clinical significance for early diagnosis and treatment of primary bone tumor.     

Decreased SFRP2 expression is associated with intermediate and poor karyotypes in de novo acute myeloid leukemia

Dysregulation of secreted frizzled-related protein 2 (SFRP2) has been found in various cancers. However, it is little known about the pattern of SFRP2 expression in acute myeloid leukemia (AML). This study was aimed to analyze the expression status of SFRP2 gene in AML patients and explore its clinical significance using real-time quantitative PCR (RQ-PCR). The level of SFRP2 expression significantly decreased in AML compared to controls (P<0.001). Receiver operating characteristic curve (ROC) analysis revealed that an area under the ROC curve (AUC) of 0.871 (P<0.001) or 0.902 (P<0.001) in discriminating all patients or cytogenetically normal (CN) patients from controls, respectively. Low level of SFRP2 expression was found more frequently in cytogenetically intermediate and poor groups (72% and 62%, respectively) than in favorable group (42%) (P<0.05). However, there was no significant difference in the rate of complete remission (CR) and overall survival between the groups with low SFRP2 and high expression (P>0.05). SFRP2 expression significantly increased after CR compared to initial diagnosis (P<0.05). These findings suggest that decreased SFRP2 expression is associated with intermediate/poor karyotypes in AML patients and detection of SFRP2 expression may be helpful to the diagnosis and disease monitoring in CN-AML.     

Decreased serum microRNA-206 level predicts unfavorable prognosis in patients with melanoma

Background and purpose: MicroRNA-206 (miR-206) acts as a tumor suppressor in melanoma cell lines. However, its clinical significance remains unclear. The aim of this study was to detect the serum level of miR-206 in patients with melanoma and to determine the feasibility of using it as a noninvasive prognostic biomarker. Methods: Expression levels of miR-206 in serum samples from 60 patients with melanoma and 30 healthy controls were detected by real-time quantitative polymerase chain reaction (q-PCR). Results: Expression levels of miR-206 in serum samples from patients with melanoma were significantly lower than those in healthy controls (P < 0.001). In addition, low serum miR-206 level was more frequently observed in patients with two or more metastatic sites (P = 0.02). Its serum level was also significantly associated with the response to treatment (P = 0.01). Moreover, melanoma patients with low serum miR-206 levels had higher clinical stage than those with high serum miR-206 levels (P < 0.001). Furthermore, melanoma patients with low serum miR-206 level had a dramatically shorter 5-year overall and disease-free survival than those with high serum miR-206 level (both P = 0.001). Multivariate analysis also identified the serum miR-206 level as an independent marker for both 5-year overall and disease-free survivals (both P = 0.01) in patients with melanoma. Conclusions: Our results offer the convincing evidence that miR-206 may be implicated in aggressive progression of melanoma. More importantly, the serum level of miR-206 may be a noninvasive prognostic biomarker for the patients with melanoma.     

Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer

Introduction: MicroRNA-124 (miR-124) has been proven dysregulated in several human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to investigate the clinical significance of miR-124 expression in NSCLC. Methods: Expression levels of miR-124 in 92 pairs of NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: miR-124 expression level was significantly lower in NSCLC tissues compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124 expression group was significantly shorter than that of high miR-124 expression group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was also significantly shorter than that of high miR-124 expression group (P < 0.05). In a multivariate Cox model, we found that miR-124 expression was an independent prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05). Conclusions: Our results offer the convincing evidence that miR-124 may play key roles in the progression of lung cancer and that the down-regulated expression of miR-124 may be independently associated with shorter OS and DFS of patients, suggesting that miR-124 might be a potential marker for further risk stratification in the treatment of lung cancer.     

Changes in levels of IL-9, IL-17, IFN-γ, dendritic cell numbers and TLR expression in peripheral blood in asthmatic children with Mycoplasma pneumoniae infection

Mycoplasma pneumoniae (MP) infection in children with asthma resulted in a more severe allergic state compared with a non-MP infected group. The infection rate of children with asthma was higher than that of the other groups, suggesting that being asthmatic may be a predisposing factor for MP infection and that the infection itself is an important co-factor in the disease progression of asthma. The number of dendritic cells (DCs) and the expression of TLR2 and TLR4 were compared in 22 asthmatic patients with MP infection, 22 asthmatic patients without MP infection, and 17 normal children as controls. The percentages of DCs in the peripheral blood of the three groups showed significant differences between asthmatic children with MP infection and controls, and asthmatic children without MP and controls (P < 0.05), whereas no difference was found between asthmatic children with and without MP infection. The asthmatic children with MP infection group showed increased expression of TLR-2 and TLR-4 on DCs (P < 0.01). Asthmatic patients infected with MP showed that DCs and TLRs (TLR-2, TLR-4) might play an important role in asthma pathogenesis with MP infection. The cytokines produced by the T-cell subsets in asthmatic children with MP infection showed a significant increase in IL-9 (P < 0.01) and a decrease in IFN-γ (P < 0.05) levels post-MP infection, while the IL-17 level remained stable (P > 0.05), indicating a shift towards Th1/Th9 in the presence of MP infection.     

Decreased expression of microRNA-20a promotes tumor progression and predicts poor prognosis of cutaneous squamous cell carcinoma

Background: MicroRNA-20a (miRNA-20a or miR-20a) plays a key role in tumorigenesis and progression. But the prognostic value of miR-20a in cutaneous squamous cell carcinoma (CSCC) remains unclear. The aim of this study was to identify the association of miR-20a and the prognosis of CSCC patients. Methods: The miR-20a expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR) in 152 CSCC tissues and matched adjacent normal tissues. Kaplan-Meier and Cox regression analysis were utilized to determine the association of miR-20a with overall survival as well as the prognosis of CSCC patients. Results: The expression of miR-20a was lower in CSCC tissues compared with adjacent normal tissues (P=0.000). Moreover, the expression of miR-20a was closely correlated with TNM stage (P=0.013). Kaplan-Meier analysis showed that patients with low miR-20a expression had significantly poorer overall survival than those with high miR-20a expression (P<0.05). Multivariate analysis revealed that miR-20a expression (P=0.001, HR=3.262, 95% CI: 1.635-6.520) could influence the prognosis and might be an independent prognostic predictor in CSCC. Conclusions: Our results indicated that low miR-20a expression was associated with tumor stage of CSCC and suggested that miR-20a expression would be a novel biomarker for predicting clinical outcomes in CSCC patients. The inhibition of miR-20a might even become a new therapeutic method for the treatment of CSCC.     

Association of the rs7395662 SNP in the MADD-FOLH1 and Several Environmental Factors with Serum Lipid Levels in the Mulao and Han Populations

Background: The rs7395662 single nucleotide polymorphism (SNP) in the MADD-FOLH1 has been associated with serum lipid traits, but the results are inconsistent in different populations. The present study was undertaken to investigate the association of rs7395662 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.Method: A total of 721 subjects of Mulao and 727 subjects of Han Chinese were randomly selected from our previous stratified randomized samples. Genotyping of the SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing.Results: Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.01). The allelic and genotypic frequencies in Han were different between males and females (P < 0.05 for each), but there was no difference between Mulao and Han or between Mulao males and females. The levels of low-density lipoprotein cholesterol (LDL-C) and ApoB in Mulao females were different among the genotypes (P < 0.05), the G allele carriers had higher LDL-C and ApoB levels than the G allele non-carriers. The levels of total cholesterol (TC), triglyceride (TG), LDL-C and ApoB in Han males and TC, TG and high-density lipoprotein cholesterol (HDL-C) in Han females were different among the genotypes (P < 0.05-0.01), the subjects with GG genotype in Han males had higher TC, TG, and ApoB and lower LDL-C levels than the subjects with AA or AG genotype, and the G allele carriers in Han females had lower TC and HDL-C levels than the G allele non-carriers. The levels of LDL-C and ApoB in Mulao females were correlated with the genotypes (P < 0.05 for each). The levels of HDL-C and ApoAI in Han males and HDL-C in Han females were correlated with genotypes (P < 0.05-0.001). Serum lipid parameters were also correlated with several environmental factors in both ethnic groups (P < 0.05-0.01).Conclusion: The association of rs7395662 SNP and serum lipid levels is different between the Mulao and Han populations, and between males and females in both ethnic groups.