Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as prognostic biomarkers in limited-stage small-cell lung cancer: a meta-analysis.

Background: The role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in limited-stage small-cell lung cancer (LS-SCLC) remains controversial. Methods: Using pooled hazard ratios (HR) with 95% CIs, we assessed the correlation of pre-treatment NLR and PLR with overall survival (OS) and progression-free survival (PFS) in LS-SCLC. Publication bias was assessed by Begg's and Egger's tests. Results: Ten studies were enrolled in our meta-analysis. Pooled analyses showed that pre-treatment high NLR was significantly associated with poor OS (HR: 1.80) and PFS (HR: 1.69) in LS-SCLC patients. High pre-treatment PLR was also associated with shorter OS (HR: 1.52) and PFS (HR: 1.39) in LS-SCLC patients. Conclusion: Our meta-analysis suggests that high pre-treatment NLR or PLR may be negatively related to OS and PFS in LS-SCLC.

LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73.

BACKGROUND: The ubiquitin protein ligase E3C (UBE3C) has been reported to play an oncogenic role in breast cancer (BRCA). This work further investigates the effect of UBE3C on the radioresistance of BRCA cells. METHODS: Molecules linking to radioresistance in BRCA were identified by analyzing two GEO datasets, GSE31863 and GSE101920. UBE3C overexpression or knockdown was induced in parental or radioresistant BRCA cells, followed by irradiation treatment. The malignant properties of cells in vitro, and the growth and metastatic activity of cells in nude mice, were analyzed. Downstream target proteins, as well as upstream transcriptional regulators of UBE3C, were predicted by bioinformatics tools. Molecular interactions were confirmed by immunoprecipitation and immunofluorescence assays. Furthermore, artificial alterations of TP73 and FOSB were induced in the BRCA cells for functional rescue assays. RESULTS: According to bioinformatics analyses, UBE3C expression was linked to radioresistance in BRCA. UBE3C knockdown in radioresistant BRCA cells reduced while its overexpression in parental BRCA cells increased the radioresistance of cells in vitro and in vivo. UBE3C, which induced ubiquitination-dependent protein degradation of TP73, was transcriptionally activated by FOSB. The radioresistance of cancer cells was blocked by TP73 overexpression or FOSB knockdown. Additionally, LINC00963 was found to be responsible for the recruitment of FOSB to the UBE3C promoter for transcription activation. CONCLUSION: This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73.

Associations between serum clusterin levels and non-alcoholic fatty liver disease.

Objective: Clusterin is closely correlated with insulin resistance and its associated comorbidities. This study aimed to investigate the correlation between serum clusterin levels and non-alcoholic fatty liver disease (NAFLD) and further explore the mediating role of insulin resistance in this relationship. Methods: This study enrolled 195 inpatients (41 males and 154 females) aged 18-61 years. Twenty-four patients were followed up for 12 months after bariatric surgery. Serum clusterin levels were measured using a sandwich enzyme-linked immunosorbent assay. Fatty liver disease was diagnosed on the basis of liver ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of hepatic steatosis. The mediating role of homeostasis model assessment-insulin resistance (HOMA-IR) was assessed using mediation analysis. Results: Participants with NAFLD had significantly higher serum clusterin levels than those without NAFLD (444.61 (325.76-611.52) mg/L vs 294.10 (255.20-373.55) mg/L, P < 0.01). With increasing tertiles of serum clusterin levels, the prevalence of NAFLD displayed an upward trend (P < 0.01). Multivariate linear regression analysis showed that serum clusterin levels were a positive determinant of FLI (standardized ß = 0.271, P < 0.001) after adjusting for multiple metabolic risk factors. Serum clusterin levels significantly decreased after bariatric surgery (298.77 (262.56-358.10) mg/L vs 520.55 (354.94-750.21) mg/L, P < 0.01). In the mediation analysis, HOMA-IR played a mediating role in the correlation between serum clusterin levels and FLI; the estimated percentage of the total effect was 17.3%. Conclusion: Serum clusterin levels were associated with NAFLD. In addition, insulin resistance partially mediated the relationship between serum clusterin levels and FLI.

A retrospective analysis of prognostic factors and treatment choices in small cell lung cancer with liver metastasis.

Background: Small cell lung cancer (SCLC) is characterized by high aggressiveness and early dissemination, with the liver being the most common site of metastasis. Although it has been established that the prognosis for SCLC with liver metastasis is exceedingly poor, comprehensive data on clinical features, prognostic factors, treatment options, and outcomes of this patient population remain limited. This retrospective study aims to examine the clinicopathological features and current treatment landscape and to identify prognostic factors associated with SCLC with liver metastasis in real-world settings. Methods: We conducted a retrospective analysis of data on SCLC patients with liver metastasis at initial diagnosis between January 1, 2013, and January 1, 2022. Kaplan-Meier analysis and log-rank tests were employed to estimate the overall survival (OS) and progression-free survival (PFS). Cox regression models were utilized to identify independent prognostic factors. Results: A total of 349 patients were included in the study, with 97.7% of patients exhibiting pure SCLC and 42.4% of patients presenting with concomitant bone metastasis. Approximately one-fourth of the patients had metastases in ≥3 organs, and 18.9% of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. The median OS was 10.97 months (95% CI: 9.88-12.06) for those who received first-line therapy (n=286). Of these, 263 patients were treated with chemotherapy, showing a median OS of 11.37 months. Furthermore, 43.8% of patients received second-line treatment, and 81 patients proceeded to third-line treatment. ECOG PS ≥2 and mixed-SCLC were identified as independent adverse prognostic factors in SCLC with liver metastasis, whereas treatments including systemic treatment alone or in combination with local radiotherapy were associated with better prognoses. Conclusions: This retrospective study substantiated that ECOG PS ≥2 and mixed SCLC are independent predictors of poor prognosis for SCLC with liver metastasis. Additionally, different treatment strategies can improve the survival of this patient population, with chemotherapy currently being the main treatment option.

Development and validation of a dynamic survival nomogram for metastatic non-small cell lung cancer based on the SEER database and an external validation cohort.

Background: Limited efficacy and poor prognosis are common in patients with metastatic non-small cell lung cancer (NSCLC). An accurate and useful nomogram helps the clinician predict the prognosis of the patients. However, there has been no previous report on the nomogram specially for predicting the overall survival (OS) of metastatic NSCLC patients. Methods: A total of 18,343 patients diagnosed with metastatic NSCLC in the Surveillance, Epidemiology, and End Results (SEER) database were included and divided into the training cohort (n=12,840) and the internal validation cohort (n=5,503), and 242 patients in Renji Hospital were additionally enrolled as the external validation cohort. Demographical, clinical, and OS data were collected. A Cox proportional hazards regression model was used to develop a nomogram based on the training cohort. To validate the nomogram, we applied C-indexes, calibration curves, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and a Kaplan-Meier survival curve. Results: The multivariate Cox regression model found that there were a total of 16 independent risk factors for OS of the patients (all 16 factors showed P<0.001), which were integrated into the nomogram with a C-index of 0.702 [95% confidence interval (CI): 0.684-0.720]. The nomogram also exhibited good prognostic value in the internal validation cohort (C-index =0.699, 95% CI: 0.673-0.725) and external validation cohort (C-index =0.695, 95% CI: 0.653-0.737). The ROC and Kaplan-Meier survival curve analyses demonstrated a high discriminative ability. High-risk patients had significantly less favorable OS than low-risk patients in the SEER population and external validation cohort (both P<0.001). The DCA analysis showed that the nomogram provided better prognosis prediction than the tumor-node-metastasis (TNM) staging system. Conclusions: We constructed and validated a dynamic nomogram with 16 variables based on a large-scale population of SEER database to predict the prognosis of metastatic NSCLC patients. The nomogram is expected to provide higher predictive ability and accuracy than the TNM staging system.

The Impact of Lymphopenia and Dosimetric Parameters on Overall Survival of Esophageal Cancer Patients Treated with Definitive Radiotherapy.

PURPOSE: The objectives of the present study are to perform a survival analysis of patients with thoracic esophageal squamous cell carcinoma (ESCC) receiving definitive radiotherapy and to identify prognostic factors from among the hematological and dosimetric factors. METHODS: Cases of thoracic ESCC treated with radical RT between 2014 and 2017 were identified. The impact of clinicopathological factors on overall survival (OS) were analyzed using the Cox proportional hazards model. Absolute lymphocyte counts (ALC) and the neutrophil-to-lymphocyte ratio (NLR = ANC/ALC) were assessed before, during, and after radiotherapy (RT). Cox regression was used to correlate clinical factors with hematologic toxicities, dosimetric parameters and overall survival. Multiple logistic regression analysis was used to identify associations between lymphopenia and dosimetric parameters. With the overall survival status and real time events, the X-tile program was utilized to determine the optimal cut-off value of pretreatment NLR, and ALC nadir. RESULTS: Ninety-nine ESCC patients were enrolled in the present study. They had a median OS of 23 months. The median RT dose was 55.75Gy (46-66Gy), and the mean dose (Dmean) of the thoracic vertebrae (TVB) was 27.04±9.65Gy. Based on the multivariate analysis, the V20 of TVB, the pretreatment NLR, and the ALC nadir were associated with significantly worse OS. Concurrent CRT, which entailed increasing the mean TVB dose and V20 of TVB, was linked to a higher probability of lymphopenia risk (P<0.05). This was ascertained through the multiple logistic regression analysis. CONCLUSION: In ESCC patients who received definitive RT, V20 of TVB, pretreatment NLR, and ALC nadir during RT were independent prognostic factors and chemotherapy regimen, mean TVB dose, and V20 of TVB were associated with lymphopenia.

The incidence and prognosis of nasopharyngeal carcinoma patients with family history.

PURPOSE: Epidemiological data showed that nasopharyngeal carcinoma (NPC) was a regional malignancy. It suggested that genetic factor may play an important role in tumorigenesis of NPC. The aim was to investigate the incidence and the prognosis of NPC patients with family history. METHODS: The clinical data of patients with NPC treated in Fudan University Shanghai Cancer Center from January 2008 to December 2012 were reviewed, and the patients with family history were selected. The prognosis of patients with family history was follow-up. The 5-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed by Kaplan-Meier and log-rank test. Cox proportional hazard model was used for multivariate analysis. RESULTS: There were 3.64% (135/3706) NPC patients with family history of NPC. Eighty-three percent (112/135) patients had only one family member suffering from NPC previously, and 74.1% (100/135) patients who had family history only in first-degree family members. Excluding five patients lost to follow-up, 130 patients were eventually used to analyze the prognosis. The 5-year OS, LRFS, and DMFS rates of all patients with family history were 84.1%, 83.4%, and 83.8%, respectively. There were no significant differences of OS, LRFS and DMFS between one relative group and at least two relatives group. In addition, the degree of NPC had no association with OS, LRFS and DMFS, respectively. CONCLUSION: Our results showed that there was an incidence rate of 3.64% NPC patients with family history. These patients had a satisfied prognosis, and the prognosis of NPC patients with family history in different degree or numbers of relatives had no significant differences.