Development and validation of a risk prediction score for patients with nasopharyngeal carcinoma.

BACKGROUND: We aimed to develop and validate a predictive model for the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC). METHODS: Overall, 519 patients were retrospectively reviewed in this study. In addition, a random forest model was used to identify significant prognostic factors for OS among NPC patients. Then, calibration plot and concordance index (C-index) were utilized to evaluate the predictive accuracy of the nomogram model. RESULTS: We used a random forest model to select the three most important features, dNLR, HGB and EBV DNA, which were significantly associated with the OS of NPC patients. Furthermore, the C-index of our model for OS were 0.733 (95% CI 0.673 ~ 0.793) and 0.772 (95% CI 0.691 ~ 0.853) in the two cohorts, which was significantly higher than that of the TNM stage, treatment, and EBV DNA. Based on the model risk score, patients were divided into two groups, associated with low-risk and high-risk. Kaplan-Meier curves demonstrated that the two subgroups were significantly associated with OS in the primary cohort, as well as in the validation cohort. The nomogram for OS was established using the risk score, TNM stage and EBV DNA in the two cohorts. The nomogram achieved a higher C-index of 0.783 (95% CI 0.730 ~ 0.836) than that of the risk score model 0.733 (95% CI 0.673 ~ 0.793) in the primary cohort (P = 0.005). CONCLUSIONS: The established risk score model and nomogram resulted in more accurate prognostic prediction for individual patient with NPC.

Establishment and Validation of Nomogram Model Integrated With Inflammation-Based Factors for the Prognosis of Advanced Non-Small Cell Lung Cancer.

OBJECTS: Inflammation is one of the hallmarks of cancer. Tumor-associated inflammatory response plays a crucial role in enhancing tumorigenesis. This study aimed to establish an effective predictive nomogram based on inflammation factors in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively evaluated 887 patients with advanced NSCLC between November 2004 and December 2015 and randomly divided them into primary (n = 520) and validation cohorts (n = 367). Cox regression analysis was used to identify prognostic factors for building the nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index), calibration plot, and decision curve analysis and were compared to the TNM staging system. RESULTS: The nomogram was established using independent risk factors (P < 0.05): age, TNM stage, C reaction protein-to-albumin ratio (CAR), and neutrophils (NEU). The C-index of the model for predicting OS had a superior discrimination power compared to that of the TNM staging system both in the primary [0.711 (95% CI: 0.675-0.747) vs 0.531 (95% CI: 0.488-0.574), P < 0.01] and validation cohorts [0.703, 95% CI: 0.671 -0.735 vs 0.582, 95% CI: 0.545-0.619, P < 0.01]. Decision curves also demonstrated that the nomogram had higher overall net benefits than that of the TNM staging system. Subgroup analyses revealed that the nomogram was a favorable prognostic parameter in advanced NSCLC (P < 0.05). The results were internally validated using the validation cohorts. CONCLUSIONS: The proposed nomogram with inflammatory factors resulted in an accurate prognostic prediction in patients with advanced NSCLC.

Combination of Plasma MIF and VCA-IgA Improves the Diagnostic Specificity for Patients With Nasopharyngeal Carcinoma.

INTRODUCTION: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques. RESULTS: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen-negative and Epstein-Barr virus viral capsid antigen-positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen. CONCLUSION: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.

Target induced framework nucleic acid nanomachine with doxorubicin-spherical nucleic acid tags for electrochemical determination of human telomerase activity.

A stable and enzyme-free method is described for highly sensitive determination of telomerase activity. It is based on the use of a framework nucleic acid (FNA) nanomachine and doxorubicin-spherical nucleic acid (DSNA) tags. Upon incubation with telomerase, the primer-tetrahedron becomes elongated to form the handed swing arm. The extended swing arm autonomously moves along the predefined track consisting of entropy-tetrahedron by consecutive strand displacement under the aid of fuel-tetrahedron. As a result, many (entropy-tetrahedron)-(fuel-tetrahedron) complexes are assembled for combining the DSNA tags. This results in an amplified electrochemical signal, typically measured at around -0.63 V (Ag/AgCl). The use of an enzyme-free FNA nanomachine and of DSNA tags warrants outstandingly high stability and sensitivity. The method shows a broad dynamic correlation of telomerase activity in cell extracts. The analytical range extends from 10 to 1.0 × 104 HeLa cells mL-1 with a lower detection limit of 2 cells mL-1. The differences in telomerase activity between different cancer cells can be easily evaluated. The method was further verified by quantifying telomerase activity of cancer cells in accumulated normal cells. Therefore, the sensing method has great potential for clinical application. Graphical abstractSchematic representation of the electrochemical biosensor based on target induced framework nucleic acid nanomachine with doxorubicin-spherical nucleic acids (DSNA) tags, which can be used to the determination of telomerase activity in accumulated normal cells. dNTP: Deoxynucleotide triphosphates; FT: Fuel-tetrahedron.

Correction: MiR-451 as a new tumor marker for gastric cancer.

[This corrects the article DOI: 10.18632/oncotarget.17239.].

MicroRNA-466 with tumor markers for cervical cancer screening.

Cervical cancer is the second most common cancer in women in the world. In this study, we explore tumor markers and microRNA-466 combination for cervical cancer screening. Tumor markers were measured by the methods of electro-chemiluminescent immunoassay and enzyme immunoassay. The microRNA-466 was performed by quantitative real-time polymerase chain reaction. Among normal group, hyperplasia group and cancer group, the CEA expression levels were 2.26 ng/ml, 3.85 ng/ml and 16.08 ng/ml, respectively. While the CA125 expression levels were 13.61 u/ml, 27.32 u/ml and 44.93 u/ml, respectively. The SCCA expression levels were 13.61 ng/ml, 27.32 ng/ml and 44.93 ng/ml, respectively. The expression levels of tumor markers were all gradually increased with the development of cervical lesions. The expression levels of microRNA-466 in cervical cancers (0.62) were greater than that in normal (0.076) and hyperplasia (0.24). The expression of microRNA-466 was correlated with lymphnode metastasis (P=0.000). There is a lower overall survival rate of patient with large tumor or lymphnode metastasis. Thus, the combination of tumor markers and microRNA-466 can be useful for early detection of cervical cancer and indicators for advanced stage and prognosis of the disease.

MiR-451 as a new tumor marker for gastric cancer.

Gastric cancer is the second most common malignancy in China. However, the prognosis for gastric cancer patients remains poor. The purpose of this study was to investigate whether miR-451 was a potential prognostic biomarker for gastric cancer. Fresh tissues were immediately frozen in liquid nitrogen until use. The plasma was extracted and quantitative real-time polymerase chain reaction was performed to detect miR-451 expression. The Student's t test analysis and multivariate Cox regression analysis were performed to analyze expression of miR-451. The analysis results showed that the expression level of miR-451 was decreased expression in gastric cancer tissue. The down-regulation of miR-451 tended to be positively correlated with tumor stage, lymphatic metastasis and shorter overall survival of patients. MiR-451 may be a potential biomarker and a potential therapeutic target for the diagnoses and prognosis of gastric cancer.

Diagnostic value of long noncoding RNAs for hepatocellular carcinoma: A PRISMA-compliant meta-analysis.

BACKGROUND: Increasing evidences have shown that long noncoding RNAs (lncRNAs) are involved in cancer diagnosis and prognosis. However, the overall diagnostic accuracy of lncRNAs for hepatocellular carcinoma (HCC) remains unclear. Herein, we perform a meta-analysis to assess diagnostic value of lncRNAs for HCC. METHODS: The online PubMed, Cochrane, Web of Science, and Embase database were searched for eligible studies published until October 5, 2016. Study quality was evaluated with the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS). All statistical analyses were conducted with Stata 12.0 and Meta-Disc 1.4. RESULTS: We included 19 studies from 10 articles with 1454 patients with HCC and 1300 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for lncRNAs in the diagnosis of HCC were 0.83 (95% confidence interval [CI]: 0.76-0.88), 0.80 (95% CI: 0.73-0.86), 4.2 (95% CI: 3.00-5.80), 0.21 (95% CI: 0.15-0.31), 20 (95% CI: 11-34), and 0.88 (95% CI: 0.85-0.91), respectively. Additionally, the diagnostic value of lncRNAs varied based on sex ratio of cases and characteristics of methods (specimen type and reference gen). CONCLUSION: This meta-analysis suggests lncRNAs show a moderate diagnostic accuracy for HCC. However, prospective studies are required to confirm its diagnostic value.

A New MicroRNA Expression Signature for Cervical Cancer.

BACKGROUND: Cervical cancer is the second most common cancer among women worldwide. The potential of microRNAs as novel biomarkers in cervical cancer is growing. OBJECTIVES: In this study, we investigated the functions and targets of miR-466 in cervical cancer tissues. METHODS: Fresh cervical tissues were obtained from 157 patients with cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy controls, and the tissues were immediately frozen in liquid nitrogen until use. The RNA was extracted and quantitative real-time polymerase chain reaction (PCR) was performed. RESULTS: A total of 157 participants were summarized, including 56 patients with cervical cancer, 60 patients with CIN, and 49 healthy controls. The expression levels of miR-466 in cervical cancers (0.68) were higher than that in healthy controls (0.082) (P < 0.01). The average fold changes of miR-466 in the patients with CIN group and people group were 0.28 and 0.082, respectively (P < 0.01). It was a statistically significant difference in patients with lymph node involvement (P = 0.022). However, the expression of miR-466 was not correlated with International Federation of Gynecology and Obstetrics stages, tumor size, or vascular invasion (P = 0.506, P = 0.667, and P = 0.108, respectively). CONCLUSIONS: Our results indicate that the aberrant expression of miR-466 is closely associated with the occurrence and development of cervical cancer.

Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.