A novel clinical model for predicting malignancy of solitary pulmonary nodules: a multicenter study in chinese population.

BACKGROUND: This study aimed to establish and validate a novel clinical model to differentiate between benign and malignant solitary pulmonary nodules (SPNs). METHODS: Records from 295 patients with SPNs in Sun Yat-sen University Cancer Center were retrospectively reviewed. The novel prediction model was established using LASSO logistic regression analysis by integrating clinical features, radiologic characteristics and laboratory test data, the calibration of model was analyzed using the Hosmer-Lemeshow test (HL test). Subsequently, the model was compared with PKUPH, Shanghai and Mayo models using receiver-operating characteristics curve (ROC), decision curve analysis (DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI) with the same data. Other 101 SPNs patients in Henan Tumor Hospital were used for external validation cohort. RESULTS: A total of 11 variables were screened out and then aggregated to generate new prediction model. The model showed good calibration with the HL test (P = 0.964). The AUC for our model was 0.768, which was higher than other three reported models. DCA also showed our model was superior to the other three reported models. In our model, sensitivity = 78.84%, specificity = 61.32%. Compared with the PKUPH, Shanghai and Mayo models, the NRI of our model increased by 0.177, 0.127, and 0.396 respectively, and the IDI changed - 0.019, -0.076, and 0.112, respectively. Furthermore, the model was significant positive correlation with PKUPH, Shanghai and Mayo models. CONCLUSIONS: The novel model in our study had a high clinical value in diagnose of MSPNs.

A multi-parametric prognostic model based on clinical features and serological markers predicts overall survival in non-small cell lung cancer patients with chronic hepatitis B viral infection.

BACKGROUND: To establish and validate a multi-parametric prognostic model based on clinical features and serological markers to estimate the overall survival (OS) in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. METHODS: The prognostic model was established by using Lasso regression analysis in the training cohort. The incremental predictive value of the model compared to traditional TNM staging and clinical treatment for individualized survival was evaluated by the concordance index (C-index), time-dependent ROC (tdROC) curve, and decision curve analysis (DCA). A prognostic model risk score based nomogram for OS was built by combining TNM staging and clinical treatment. Patients were divided into high-risk and low-risk subgroups according to the model risk score. The difference in survival between subgroups was analyzed using Kaplan-Meier survival analysis, and correlations between the prognostic model, TNM staging, and clinical treatment were analysed. RESULTS: The C-index of the model for OS is 0.769 in the training cohorts and 0.676 in the validation cohorts, respectively, which is higher than that of TNM staging and clinical treatment. The tdROC curve and DCA show the model have good predictive accuracy and discriminatory power compare to the TNM staging and clinical treatment. The prognostic model risk score based nomogram show some net clinical benefit. According to the model risk score, patients are divided into low-risk and high-risk subgroups. The difference in OS rates is significant in the subgroups. Furthermore, the model show a positive correlation with TNM staging and clinical treatment. CONCLUSIONS: The prognostic model showed good performance compared to traditional TNM staging and clinical treatment for estimating the OS in NSCLC (HBV+) patients.

Downregulation of miR-182-5p inhibits the proliferation and invasion of triple-negative breast cancer cells through regulating TLR4/NF-κB pathway activity by targeting FBXW7.

BACKGROUND: To investigate the role of miR-182-5p in the proliferation and invasion of triple-negative breast cancer (TNBC) cells, as well as the underlying mechanism. METHODS: qRT-PCR was used to detect the level of miR-182-5p in tissues and cells. CCK-8 assay, flow cytometry, and Transwell assay were performed to detect cell proliferation, apoptosis rate, and invasion, respectively. Pearson correlation analysis was used to determine the correlation between miR-182-5p and its predicted target gene FBXW7, and the target of miR-182-5p was identified by dual-luciferase reporter gene assay. ELISA assay was used to examine the levels of cytokines in the culture supernatant of tumor cells. Western blot analysis was used to detect the expressions of FBXW7, TLR4, and NF-κB) pathways in tumor cells. RESULTS: In MDA-MB-231 and BT-549 cells, downregulation of miR-182-5p significantly inhibited cell proliferation and invasion and promoted tumor cell apoptosis. Pearson correlation analysis showed that miR-182-5p had a negative correlation with FBXW7. Dual-luciferase reporter gene assay showed that miR-182-5p could directly target FBXW7. Further studies showed that FBXW7 overexpression significantly inhibited cell proliferation and invasion and increased the apoptosis rate. Downregulation of miR-182-5p significantly reduced the levels of TNF-α, IL-1 ß, IL-6, and IL-18 in the culture supernatant, and decreased the activity of TLR4/NF-κB pathway in tumor cells, while downregulation of FBXW7 significantly inhibited the effect of miR-182-5p on tumor cells. CONCLUSIONS: Downregulation of miR-182-5p inhibits TLR4/NF-κB pathway activity by increasing FBXW7 expression, thereby suppressing the proliferation and invasion of TNBC cells.

The prognostic value of integration of pretreatment serum amyloid A (SAA)-EBV DNA (S-D) grade in patients with nasopharyngeal carcinoma.

BACKGROUND: Serum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA-EBV DNA (S-D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S-D grade was calculated based on the cut-off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S-D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S-D grade with TNM staging system using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S-D grade was divided into S-D grade 1, S-D grade 2, and S-D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices. CONCLUSIONS: We found that the S-D grade could be used as a new tool to predict the OS in NPC patients.

Prognostic nomogram integrated baseline serum lipids for patients with non-esophageal squamous cell carcinoma.

BACKGROUND: Serum lipids have been documented as prognostic biomarkers in several types of cancer, however the prognostic value of serum lipids in non-esophageal squamous cell carcinoma (non-ESCC) is not clear. The purpose of this study was to investigate the prognostic roles of serum lipids in non-ESCC and to establish a novel effective nomogram for overall survival (OS) and disease-free survival (DFS) in patients with non-ESCC. METHODS: We retrospectively analyzed the prognostic values of pretreatment serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteinA-I (ApoAI), and apolipoprotein B (ApoB) and three lipid derivatives: atherogenic index [AI: (TC-HDL-C)/HDL-C], THR (TG/HDL-C) and LHR (LDL-C/HDL-C) in non-ESCC patients. Prognostic factors predictive of OS and DFS were determined by univariate and cox hazards analysis, and prognostic nomograms were established. The predictive power of independent prognostic factors was compared adopting time-dependent ROC. Comparisons between the nomograms and traditional TNM staging systems were evaluated using the C-index and decision curve analysis. RESULTS: A total of 180 non-ESCC patients were recruited in this prospective study between January 2006 and December 2016. Four (cancer type, TNM stage, TC, and TG) and five (cancer type, TNM stage, TC, TG, and LDL-C) independent prognostic factors were chosen to generate the nomogram for OS and DFS, respectively. Our results showed that the area under curves (AUCs) of cancer type and TG were higher than TNM stage for OS. For DFS, however, AUCs of cancer type, TG and LDL-C were higher than the TNM stage. The C-index of the nomogram for predicting the OS was 0.69, which was significantly higher than that of TNM stage (0.58, P=0.005). In addition, for DFS, the C-index of the nomogram was significantly higher than that of the TNM stage (0.70 vs. 0.60, P=0.001). Furthermore, decision curve analysis showed that the predictive accuracy of the prognostic nomogram for OS and DFS were both higher than the TNM stage. CONCLUSIONS: Our study demonstrated that pretreatment of serum lipids based on the prognostic nomogram could be applied to predict the OS and DFS in non-ESCC patients.

Lack of association between the distribution of ABO blood groups and nasopharyngeal carcinoma in a population of Southern China.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The ABO blood group antigens are chemical constituents on the surface of red blood cells and various epithelial cells. Several studies have described the association of ABO blood types with multiple types of human cancer. In this study, we aimed to investigate the relationship between the incidence of NPC and ABO blood groups. MATERIALS AND METHODS: We retrospectively analyzed the files of 1136 pathologically confirmed patients with NPC and 1024 cancer-free healthy controls, including the information of serologically determined blood group. The distribution of blood groups between patients with NPC and the control group was determined. The Chi-square test was applied to assess the distribution of age, gender, smoking, family history, and ABO blood groups between the NPC and the controls. Pearson's correlation was performed to evaluate the correlation between ABO blood groups and clinical stages. RESULTS: There was no significant difference in age, smoking, family history, and ABO blood group between patients with NPC and the control group (P > 0.05). ABO blood groups were also not associated with NPC stages (P = 0.506). However, the proportion of males with NPC was higher than that of control group (P < 0.01). CONCLUSION: The blood group types were not associated with increased risk of NPC and NPC stages in a population of Southern China.

Prognostic nomogram for patients with Nasopharyngeal Carcinoma incorporating hematological biomarkers and clinical characteristics.

Predictive models for survival prediction in individual cancer patients following the tumor, node, and metastasis (TNM) staging system are limited. The survival rates of patients who share TNM stage diseases are diversified. Therefore, we established a nomogram in which hematological biomarkers and clinical characteristics for predicting the overall survival (OS) of nasopharyngeal carcinoma (NPC) patients were incorporated. The clinicopathological and follow-up data of 690 NPC patients who were histologically diagnosed histologically at the Sun Yat-sen University Cancer Center between July 2007 and December 2011 were retrospectively reviewed. Data was randomly divided into primary (n = 460) and validation groups (n = 230). Cox regression analysis was used to identify prognostic factors for building the nomogram in primary cohorts. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index) and decision curve, and were compared with the TNM staging system, Epstein-Barr virus DNA copy numbers (EBV DNA), or TMN stage plus EBV DNA. The results were internally validated by assessment of discrimination and calibration using the validation cohorts at the same institution. Independent factors selected into the nomogram for OS included age [hazard ratio (HR): 1.765; 95% confidence interval (CI): 1.008-3.090)], TNM stage (HR: 1.899; 95% CI: 1.023-3.525), EBV DNA (HR: 1.322; 95% CI: 1.087-1.607), lactate dehydrogenase level (LDH) (HR: 1.784; 95% CI: 1.032-3.086), high sensitivity C-reactive protein (hs-CRP) (HR: 1.840; 95% CI: 1.039-3.258), high-density lipoprotein cholesterol (HDL-C) (HR: 0.503; 95% CI: 0.282-0.896), hemoglobin (HGB) (HR: 0.539; 95% CI: 0.309-0.939) and lymphocyte to lymphocyte ratio (LMR) (HR:0.531; 95% CI: 0.293-0.962). The C-index in the primary cohort and validation cohort were 0.800 and 0.831, respectively, and were statistically higher when compared to C-index values for TNM stage (0.672 and 0. 716), EBV DNA (0.668 and 0.688), and TNM stage+ EBV DNA (0. 732 and 0. 760), P < 0.001 for all. Moreover, the decision curve analyses demonstrated that the nomogram model had a higher overall net benefit compared to the TNM staging system, EBV DNA and TNM stage+ EBV DNA. Next, patients were divided into three distinct risk groups for OS based on total points (TPs) of the nomogram: a low-risk group (TPs ≤ 19.0), an intermediate risk group (19.0 < TPs ≤ 25.5) and a high risk group (TPs > 25.5), respectively. The nomogram predicting prognosis generated for NPC patients had a higher predictive power compared to the TNM staging system, EBV DNA, and TNM stage+ EBV DNA.

Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

BACKGROUND: This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. METHODS: The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. RESULTS: Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P < 0.01], and the decision curve analyses showed that the nomogram model had a higher overall net benefit than did the TNM stage. Based on the total prognostic scores (TPS) of the nomogram, we further subdivided the study cohort into three groups: low risk (TPS ≤ 13.5), intermediate risk (13.5 < TPS ≤ 20.0) and high risk (TPS > 20.0). CONCLUSION: The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

[Value of percentage of highly fluorescent lymphocytic cells for rapidly assessing septicemia in tumor patients].

OBJECTIVE: To evaluate the value of percentage of highly fluorescent lymphocytic cells (HFLC%) for rapidly assessing septicemia in tumor patients. METHODS: Blood samples were collected from 130 patients with tumors (60 septicemia patients and 70 non-septicemia patients) and 80 healthy controls. HFLC% was analyzed with Sysmex XE-5000, the level of C-reactive protein (CRP) measured with a commercially available turbidimetric immunoassay kit and the level of procalcitonin (PCT) determined with a semiquantitative chromatographic immunoassay kit. The diagnostic values of HFLC% and CRP in septicemia were evaluated with ROC analysis. RESULTS: The values of HFLC% and CRP were significantly higher in the septicemia group than those in the non-septicemia and healthy groups (0.30% (0.10%-0.70%) vs 0.10% (0-0.20%), 0.10% (0-0.20%) ; 80.3 (28.5-129.5) vs 3.3 (1.4-41.4) , 1.4 (0.6-2.5) mg/L, all P < 0.01) . The ROC-AUCs for HFLC% and CRP for a diagnosis of septicemia were 0.72 (sensitivity 71.7%, specificity 58.7%) and 0.92 (sensitivity 96.7%, specificity 82.0%). Both of them could judge septicemia better. Additionally, HFLC% was correlated with the levels of PCT and CRP (r = 0.637, 0.241, both P < 0.01). CONCLUSIONS: HFLC% may be used as a rapid and simple auxiliary indicator in the diagnosis of septicemia in patients with tumors. And it is conducive to make an early diagnosis of septicemia and avoid unnecessary use of antibiotics.

Utility of neut-X, neut-Y and neut-Z parameters for rapidly assessing sepsis in tumor patients.

BACKGROUND: The Sysmex XE-5000 hematology analyzer evaluates toxic granulation and the nuclear maturity of toxic granulation neutrophils via the parameters neut-X and neut-Y. This study investigated whether neut-X and neut-Y could facilitate the auxiliary diagnosis of sepsis. METHODS: Blood samples were collected from 113 patients with tumors and 130 healthy individuals to detect neut-X, neut-Y, and C-reactive protein (CRP) values. Then, we created a new parameter, neut-Z, the vector sum of neut-X and neut-Y. Furthermore, we assessed procalcitonin (PCT) concentrations in patients with sepsis and compared the values with those for neut-X, neut-Y, and neut-Z. RESULTS: Neut-X, neut-Y, neut-Z, and CRP values were significantly higher in the sepsis group than in the non-sepsis and healthy groups. The ROC-AUCs for neut-X, neut-Y, neut-Z, and CRP for a diagnosis of sepsis were 0.87 (sensitivity 82%, specificity 79%), 0.87 (78 and 94%, respectively), 0.91 (82 and 88%, respectively), and 0.95 (96 and 89%, respectively), respectively. Additionally, neut-X, neut-Y, and neut-Z were correlated with CRP and PCT levels. CONCLUSIONS: Neut-X and neut-Y can be used as rapid and simple auxiliary indicators in the diagnosis of sepsis in patients with tumors, and neut-Z appears to display better performance than its 2 components.

[Assessment of detection assays of Epstein-Barr viral Rta-IgG, VCA-IgA, EA-IgA and Epstein-Barr viral DNA at different clinical stages in the diagnosis of nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the values of combined detection method of EB viral Rta-IgG, VCA-IgA, EA-IgA and EB viral DNA in the diagnosis of nasopharyngeal carcinoma (NPC). METHODS: Serum and plasma samples from 131 untreated NPC patients, 52 non-NPC patients with NPC-like symptoms and 148 healthy donors from January to December 2012 were collected. Immunoenzymatic staining was used to detect VCA-IgA and EA-IgA in sera. ELISA was performed to detect Rta-IgG antibody in sera and real-time fluorescent quantitative PCR for measuring EBV DNA in plasma. The clinical characteristics of 3 groups were compared. ROC curve and correlation analyses were performed to assess the detection assays for the diagnosis of NPC. RESULTS: The positive rates of EBV Rta-IgG, VCA-IgA, EA-IgA and EBV DNA in untreated NPC patient group were higher than those in other two groups. The differences were statistically significant (all P < 0.01). The differences of Rta-IgG antibody positive rates, EBV-DNA levels and EBV-DNA positive rates at different clinical stages were statistically significant (all P < 0.05). The positive rates of VCA-IgA and EA-IgA were not related with clinical stages (P > 0.05). Areas under ROC curve for Rta-IgG and EBV-DNA were 0.901 and 0.827 respectively. All four diagnostic assays demonstrated excellent efficiency. The sensitivity and specificity of individual assays were as follows: Rta-IgG: 77.9%, 92.5%; VCA-IgA 93.1%, 91.5%; EA-IgA: 74.8%, 99.5%; EBV-DNA 64.9%, 97.0%. The sensitivity and specificity of combined assays were 97.7% and 83.5% respectively. CONCLUSION: Combined detection method of EB viral Rta-IgG, VCA-IgA, EA-IgA and EB viral DNA are efficient for the diagnosis of NPC.