Identification of CCL20 as a Prognostic Predictor for Severe Fever With Thrombocytopenia Syndrome Based on Plasma Proteomics.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. METHODS: Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 nonsurvivors of SFTS. Validation was performed in a cohort of 154 patients with SFTS via enzyme-linked immunosorbent assay. We utilized the Drug-Gene Interaction Database to identify protein-drug interactions. RESULTS: Nonsurvivors exhibited 110 differentially expressed proteins as compared with survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen differentially expressed proteins-including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha, and pleiotrophin-were associated with multiple-organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohorts, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 Food and Drug Administration-approved drugs targeting 37 death-related plasma proteins. CONCLUSIONS: Distinct plasma proteomic profiles characterize SFTS cases with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.

Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients with Advanced Non-Small Cell Lung Cancer Treated with a Combination Therapy of Anti-PD-1/-PD-L1 Antibodies and Platinum-Based Chemotherapy: A Multicenter Retrospective Study.

INTRODUCTION: Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. METHODS: We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. RESULTS: The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06-2.86; p = 0.031). CONCLUSION: The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

Predictive Factors Associated with Long-Term Response to Combination Immunotherapy in Patients with Untreated Advanced Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. METHODS: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. RESULTS: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. CONCLUSION: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.

Log odds of positive lymph nodes as a novel prognostic predictor for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to summarize the predictive and prognostic ability of the log odds of positive lymph nodes (LODDS) staging system and compare it with pathological N (pN) classification and the ratio-based lymph node system (rN) for the overall survival (OS) of gastric cancer (GC). METHODS: Through a systematic review till March 7, 2022, we identified population-based studies that reported the prognostic effects of LODDS in patients with GC. We compare the predictive effectiveness of the LODDS staging system with that of the rN and pN classification systems for the OS of GC. RESULTS: Twelve studies comprising 20,312 patients were included in this systematic review and meta-analysis. The results showed that LODDS1, LODDS2, LODDS3, and LODDS4 in GC patients were correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.62, 95% CI (1.42, 1.85); LODDS2 vs. LODDS0: HR = 2.47, 95% CI (2.02, 3.03); LODDS3 vs. LODDS0: HR = 3.15, 95% CI (2.50, 3.97); LODDS4 vs. LODDS0: HR = 4.55, 95% CI (3.29, 6.29)). Additionally, significant differences in survival were observed among patients with different LODDS classifications (all P-values were < 0.001) with the same rN and pN classifications. Meanwhile, for patients with different pN or rN classifications with the same LODDS classification, prognosis was highly similar. CONCLUSION: The findings show that LODDS is correlated with the prognosis of GC patients and is superior to the pN and rN classifications for prognostic assessment.

The prognostic impact of inflammation in patients with decompensated acute heart failure, as assessed using the pan-immune inflammation value (PIV).

There is increasing evidence that composite scores based on blood counts, which are reflectors of uncontrolled inflammation in the development and progression of heart failure, can be used as prognostic biomarkers in heart failure patients. The prognostic effects of pan-immune inflammation (PIV) as an independent predictor of in-hospital mortality in patients with acute heart failure (AHF) were evaluated based on this evidence. The data of 640 consecutive patients hospitalized for New York Heart Association (NYHA) class 2-3-4 AHF with reduced ejection fraction were analyzed and 565 patients were included after exclusion. The primary outcome was in hospital all-cause death. Secondary outcomes were defined as the following in-hospital events: Acute kidney injury (AKI), malignant arrhythmias, acute renal failure (ARF) and stroke. The PIV was computed using hemogram parameters such as lymphocytes, neutrophils, monocytes and platelets. Patients were categorized as low or high PIV group according to the median value, which was 382.8. A total of 81 (14.3%) in-hospital deaths, 31 (5.4%) AKI, 34 (6%) malignant arrhythmias, 60 (10.6%) ARF and 11 (2%) strokes were reported. Patients with high PIV had a higher in-hospital mortality rate than patients with low PIV (OR: 1.51, 95% CI, 1.26-1.80, p < 0.001). Incorporating PIV into the full model significantly improved model performance (odds ratio X2, p < 0.001) compared to the baseline model constructed with other inflammatory markers. PIV is a potent predictor of prognosis with better performance than other well-known inflammatory markers for patients with AHF.

Red blood cell distribution width/platelet ratio on admission as a predictor for in-hospital mortality in patients with acute myocardial infarction: a retrospective analysis from MIMIC-IV Database.

BACKGROUND: Red blood cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory indicator. It integrates the risk prediction of RDW and platelet, which is associated with adverse outcomes. However, the predictive power of RPR in mortality for patients with acute myocardial infarction (AMI) remains uncertain. Thus, we aimed to explore the association between RPR and 180-day in-hospital mortality in patients with AMI. METHODS: Data on patients with AMI were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients were divided into two groups according to the optimal RPR cut-off value. The survival curve between high and low RPR groups was plotted via the Kaplan-Meier (KM) method. Univariate and multivariate Cox regression analyses were performed to determine the association between RPR on admission and 180-day in-hospital mortality. RESULTS: A total of 1266 patients were enrolled, of which 83 (6.8%) died within 180 days during the hospitalization. Compared with the survivor group, the non-survivor group had higher RPR on admission (0.11 ± 0.07 vs. 0.08 ± 0.06, P < 0.001). The KM curve indicated that the survival probability of low RPR group was higher than that of high RPR group. Multivariate Cox regression analysis demonstrated that higher RPR on admission was an independent and effective predictor of 180-day mortality in patients with AMI (hazard ratio [HR]: 2.677, 95% confidence interval [CI]: 1.159-6.188, P = 0.021). CONCLUSION: Higher RPR was associated with higher in-hospital 180-day mortality in patients with AMI.

Prognostic predictors and echocardiographic time course after device replacement in patients treated chronically with cardiac resynchronization therapy devices.

The prognostic predictors of death or heart failure hospitalization and the echocardiographic response after initial cardiac resynchronization therapy (CRT) device replacement (CRT-r) remain unclear. We evaluated the predictors and the echocardiographic time course in patients after CRT-r. Consecutive 60 patients underwent CRT-r because of battery depletion. Patients were divided into two groups depending on the chronic echocardiographic response to CRT (left ventricular end-systolic volume [LVESV] reduction of ≥ 15%) at the time of CRT-r: CRT responders (group A; 35 patients) and CRT nonresponders (group B; 25 patients). The primary endpoint was a composite of death from any cause or heart failure hospitalization. Changes in LVESV and left ventricular ejection fraction (LVEF) after CRT-r were also analyzed. During the mean follow-up of 46 ± 33 months after CRT-r, the primary endpoint occurred more frequently in group B (group A versus group B; 8/35 [23%] patients versus 19/25 [76%] patients, p < 0.001). No significant changes in LVESV and LVEF were observed at the mean of 46 ± 29 months after CRT-r in both groups. A multivariate analysis identified echocardiographic nonresponse to CRT, chronic kidney disease, atrial fibrillation, and New York Heart Association functional class III or IV at the time of CRT-r as independent predictors of the primary endpoint in all patients. Residual echocardiographic nonresponse, comorbidities, and heart failure symptoms at the time of CRT-r predict the subsequent very long-term prognosis after CRT-r. No further echocardiographic response to CRT was found after CRT-r.

Characteristics, prognostic factors, and chronological trends of out-of-hospital cardiac arrests with shockable rhythms in Taiwan - A 7-year observational study.

BACKGROUND: The study aimed to explore the characteristics, predictors, and chronological trends of outcomes for adult out-of-hospital cardiac arrests (OHCAs) with shockable rhythms. METHODS: A 7-year, community-wide observational study using an Utstein-style registry was conducted. Patients who were not transported, those who experienced trauma and those who lacked electronic electrocardiography data were excluded; those with initial shockable rhythms of ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) were included. Outcomes were survival of discharge (SOD) and favorable neurological status (CPC 1-2). The outcome predictors, chronological trends, and their relationship with system interventions were analyzed. RESULTS: Of the 1544 shockable OHCAs (incidence 12.6%) included, 97.6% had VF and 2.4% had pVT. VF showed better outcomes than pVT. Predictors for both outcomes (SOD; CPC 1-2) were chronological change (adjusted odds ratio [aOR]: 1.133; 1.176), younger age (aOR: 0.973; 0.967), shorter response time (aOR: 0.998; 0.999), shorter scene time (aOR: 0.999; 0.999), witnessed collapse (aOR: 1.668; 1.670), and bystander cardiopulmonary resuscitation (BCPR) (aOR: 1.448; 1.576). Predictors for only SOD were public location (aOR: 1.450) and successful prehospital defibrillation (aOR: 3.374). The use of the supraglottic airway was associated with adverse outcomes. Chronologically with system interventions, BCPR rate, the proportion of shockable OHCA, and improved neurological outcomes increased over time. CONCLUSION: The incidence of shockable OHCA remained low in Asian community. VF showed better outcomes than pVT. Over time, the incidence of shockable rhythm, BCPR rate and patient outcomes did improve with health system interventions. The number of prehospital defibrillations did not predict outcomes.

Prediction of Prognosis in Patients with Trauma by Using Machine Learning.

Background and Objectives: We developed a machine learning algorithm to analyze trauma-related data and predict the mortality and chronic care needs of patients with trauma. Materials and Methods: We recruited admitted patients with trauma during 2015 and 2016 and collected their clinical data. Then, we subjected this database to different machine learning techniques and chose the one with the highest accuracy by using cross-validation. The primary endpoint was mortality, and the secondary endpoint was requirement for chronic care. Results: Data of 5871 patients were collected. We then used the eXtreme Gradient Boosting (xGBT) machine learning model to create two algorithms: a complete model and a short-term model. The complete model exhibited an 86% recall for recovery, 30% for chronic care, 67% for mortality, and 80% for complications; the short-term model fitted for ED displayed an 89% recall for recovery, 25% for chronic care, and 41% for mortality. Conclusions: We developed a machine learning algorithm that displayed good recall for the healthy recovery group but unsatisfactory results for those requiring chronic care or having a risk of mortality. The prediction power of this algorithm may be improved by implementing features such as age group classification, severity selection, and score calibration of trauma-related variables.

An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation.

BACKGROUND: Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making. METHODS: Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. Model with the best performance was validated in an independent dataset involving 195 adult LT cases from October 2019 to March 2021. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms. RESULTS: 430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66 to 0.79) and sensitivity (0.74, CI 0.66 to 0.8) in the internal validation set, and a comparable AUC (0.75, CI 0.67 to 0.81) in the external validation set. High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model. CONCLUSIONS: Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.

Impact of an MT-RNR1 Gene Polymorphism on Hepatocellular Carcinoma Progression and Clinical Characteristics.

Mitochondrial DNA (mtDNA) mutations are highly associated with cancer progression. The poor prognosis of hepatocellular carcinoma (HCC) is largely due to high rates of tumor metastasis. This emphasizes the urgency of identifying these patients in advance and developing new therapeutic targets for successful intervention. However, the issue of whether mtDNA influences tumor metastasis in hepatoma remains unclear. In the current study, multiple mutations in mtDNA were identified by sequencing HCC samples. Among these mutations, mitochondrially encoded 12S rRNA (MT-RNR1) G709A was identified as a novel potential candidate. The MT-RNR1 G709A polymorphism was an independent risk factor for overall survival and distant metastasis-free survival. Subgroup analysis showed that in patients with cirrhosis, HBV-related HCC, α-fetoprotein ≥ 400 ng/mL, aspartate transaminase ≥ 31 IU/L, tumor number > 1, tumor size ≥ 5 cm, and histology grade 3-4, MT-RNR1 G709A was associated with both shorter overall survival and distant metastasis-free survival. Mechanistically, MT-RNR1 G709A was clearly associated with hexokinase 2 (HK2) expression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel associations among MT-RNR1 G709A and HK2 are an important risk factor in HCC patients.

Psoas cross-sectional area as a predictor of mortality and a diagnostic tool for sarcopenia in hip fracture patients.

This study aimed to determine: (1) the association between psoas cross-sectional area (PCA) and mortality in hip fracture patients, and (2) the usefulness of PCA as a diagnostic tool for sarcopenia. A total of 373 female and 121 male hip fracture patients aged 50 years or more who had surgical repair of their hip fracture between 2011 and 2017 were analyzed. PCA was measured at L4-L5 disc level using CT. PCA of gender-specific 20th percentile determined from this study cohort was used as a cutoff value. The effect of decreased PCA on mortality was analyzed. The association between PCA and appendicular lean mass (ALM) or/and grip strength was analyzed. In survival time of both genders, a significant difference was found between patients with the lowest quintile and upper 4 quintiles (p < 0.001 for females, p = 0.040 for males). The lowest quintile of PCA was associated with mortality, with hazard ratio (HR) of 2.33 (95% CI 1.44-3.47, p < 0.001) in females and 2.01 (95% CI 1.01-3.98, p = 0.046) in males. After adjustment of age, American Society of Anesthesiologists classification, body mass index, dementia, and a grip strength, the lowest quintile of PCA was significantly associated with mortality only in females, with HR of 1.76 (95% CI 1.05-2.70, p = 0.017). A moderate association between PCA and ALM was found in both genders (r = 0.358 for females, r = 0.455 for males). In conclusion, measurement of PCA has potential as a prognostic predictor and diagnostic tool for sarcopenia.

CT-Detected Extramural Vessel Invasion and Regional Lymph Node Involvement in Stage T4a Gastric Cancer for Predicting Progression-Free Survival.

OBJECTIVE. This study aimed to investigate the 3-year progression-free survival (PFS) of patients with stage T4a gastric cancer with extramural vessel invasion (EMVI) detected with contrast-enhanced (CE) MDCT. In addition, we investigated the possibility that CT of EMVI could improve clinical nodal (N) staging. MATERIALS AND METHODS. This retrospective study included 143 patients with T4a gastric cancer. Clinical staging was performed with CE-MDCT. All patients underwent radical gastrectomy with extended lymphadenectomy, adjuvant chemotherapy, and conventional follow-up visits. Potential prognostic factors, including CE-MDCT-detected N status, pathologic N status, EMVI detected at CT, tumor location or growth pattern, histologic type or tumor differentiation, and tumor size, were recorded. Survival estimates for PFS were obtained using the Kaplan-Meier product limit for the following patient subgroups: EMVI positive-N positive, EMVI positive-N negative, EMVI negative-N positive, and EMVI negative-N negative. Hazard ratios for 3-year PFS were generated using a Cox proportional hazard regression analysis. RESULTS. The frequency of EMVI detected at CT was 55.9% (80/143). The 3-year PFS rates were 25.0% for the EMVI positive-N positive group, 53.1% for the EMVI positive-N negative group, 75.6% for the EMVI negative-N positive group, and 64.7% for the EMVI negative-N negative group. The EMVI positive-N positive subgroup 3-year PFS rate was significantly lower than that of the other three groups (p < 0.05, log-rank test). Using Cox proportional hazards regression analysis, EMVI positive-N positive status was found to be an independent factor for reduced 3-year PFS, with a hazard ratio of 2.169 (95% CI, 1.300-3.618; p = 0.003). CONCLUSION. EMVI detected at CT, combined with N status detected with CE-MDCT, could be used as a valuable preoperative prognostic factor in patients with T4a gastric cancer.

Growth hormone-releasing hormone receptor antagonists inhibit human gastric cancer through downregulation of PAK1-STAT3/NF-κB signaling.

Gastric cancer (GC) ranks as the fourth most frequent in incidence and second in mortality among all cancers worldwide. The development of effective treatment approaches is an urgent requirement. Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) have been found to be present in a variety of tumoral tissues and cell lines. Therefore the inhibition of GHRH-R was proposed as a promising approach for the treatment of these cancers. However, little is known about GHRH-R and the relevant therapy in human GC. By survival analyses of multiple cohorts of GC patients, we identified that increased GHRH-R in tumor specimens correlates with poor survival and is an independent predictor of patient prognosis. We next showed that MIA-602, a highly potent GHRH-R antagonist, effectively inhibited GC growth in cultured cells. Further, this inhibitory effect was verified in multiple models of human GC cell lines xenografted into nude mice. Mechanistically, GHRH-R antagonists target GHRH-R and down-regulate the p21-activated kinase 1 (PAK1)-mediated signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB) inflammatory pathway. Overall, our studies establish GHRH-R as a potential molecular target in human GC and suggest treatment with GHRH-R antagonist as a promising therapeutic intervention for this cancer.

[18F]Fluorodeoxyglucose uptake by positron emission tomography predicts outcomes for oropharyngeal and hypopharyngeal cancer treated with definitive radiotherapy.

This study evaluated the prognostic significance of the maximum standardized uptake value of the primary site (pSUVmax) in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of patients with oropharyngeal or hypopharyngeal cancer who were treated using definitive radiotherapy. The study included 86 patients who were primarily treated with radiotherapy for oropharyngeal or hypopharyngeal cancer. Sixty-nine patients underwent concurrent chemotherapy. The associations between pre-treatment pSUVmax and treatment outcomes were evaluated. The most appropriate pSUVmax cut-off value for predicting disease-free survival (DFS) and local control (LC) was selected using receiver operating characteristic (ROC) curves. The median follow-up time for surviving patients was 60 months, while the median survival time in the entire patient cohort was 55 months. A pSUVmax cut-off value of 9.0 showed the best discriminative performance. Five-year OS and DFS rates were 65.9% and 60.0%, respectively. In univariate analyses, pSUVmax (p = 0.009), T-stage (p = 0.001), N-stage (p = 0.039), and clinical stage (p = 0.017) were identified as significant prognostic predictors for DFS. The multivariate analysis did not identify any statistically significant factors, but the association between pSUVmax and DFS was borderline significant (p = 0.055). Interestingly, pSUVmax was predictive of local controllability in T1-T2 disease (p = 0.024), but there was no significant association for T3-T4 disease (p = 0.735). In this study, pSUVmax was predictive of DFS and LC in patients with oropharyngeal or hypopharyngeal cancer that was treated with definitive radiotherapy. pSUVmax was strongly associated with LC in T1-T2 disease.

A prognostic risk model for patients with triple negative breast cancer based on stromal natural killer cells, tumor-associated macrophages and growth-arrest specific protein 6.

The aim of this study was to establish a prognostic risk model for patients with triple negative breast cancer (TNBC). A total of 278 specimens of human TNBC tissues were investigated by immunohistochemistry for growth-arrest specific protein 6 expression, infiltrations of stromal natural killer cells and tumor-associated macrophages. According to their prognostic risk scores based on the model, patients were divided into three groups (score 0, 1-2, 3). Correlations of prognostic risk scores, clinicopathologic features and overall survival (OS) were analyzed. To study the clinical value of this stratification model in early disease recurrence or metastasis, 177 patients were screened out for further analysis. Based on disease free survival (DFS), 90 patients fell within the DFS ≤3 years group and 87 patients within the DFS ≥5 years group. We analyzed the differences in prognostic risk scores between the two groups. The prognostic risk scores were negatively related to tumor size, lymph node metastasis and P53 status (P < 0.001 for all). Patients with low prognostic risk scores had longer OS (P = 0.001). Using multivariate analysis, it was determined that TNM stage (HR = 0.432, 95% confidence interval [CI] = 0.281-0.665, P = 0.003), FOXP3 positive lymphocytes (HR = 1.712, 95% CI = 1.085-2.702, P = 0.021) and prognostic risk scores (HR = 1.340, 95% CI = 1.192-1.644, P = 0.005) were independent prognostic factors for OS. Compared with the DFS ≥5 years group, the DFS ≤3 years group patients had significantly higher prognostic risk scores (P < 0.001). In conclusion, the prognostic risk score of the model was a significant indicator of prognosis for patients with TNBC.

Overexpression of lncRNA H19/miR-675 promotes tumorigenesis in head and neck squamous cell carcinoma.

There is accumulating evidence indicating that long non-coding RNA H19 and its mature product miR-675 play essential roles for tumor growth and progression. However, their prognostic value in human head and neck squamous cell carcinoma (HNSCC), particular in laryngeal carcinoma, remains to be elucidated. In this study, we observed that both H19 and miR-675 were significantly overexpressed in a cohort of 65 primary tumor samples and two HNSCC cell lines. Importantly, when paired with patient follow-up data, higher expression of either H19 or miR-675 was significantly correlated with higher risk of patient relapse, and associated with worse overall survival and poor disease-free survival. Knockdown miR-675 caused significant reduction of cell viability, migratory and invasive capabilities. Taken together, these results suggest that the strong correlation of H19 overexpression together with higher miR-675 and lymph node metastases could be useful predictive markers, indicating a potentially therapeutic strategy for HNSCC patients.

Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: It is now widely recognized that outcomes in cancer patients are not determined by their tumor characteristics alone. In this study, we retrospectively analyzed the clinical data of esophageal cancer patients to evaluate the impact of red blood cell distribution width (RDW), platelet distribution width (PDW), and mean platelet volume (MPV) on cancer-specific survival (CSS). STUDY DESIGN: We retrospectively reviewed a database of 144 consecutive patients who underwent curative esophagectomy for esophageal squamous cell carcinoma at our institute between 2006 and 2014. RESULT: In multivariate analysis, pathological stage (pStage) (p = 0.0002) and a high RDW (p = 0.0300) were found to be independently associated with poor survival. Patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.004). Among non-elderly patients, multivariate analysis demonstrated that pStage (p = 0.0120), and a high RDW (p = 0.0092) were independent risk factors for a worse prognosis. In addition, non-elderly patients with a high RDW had a significantly poorer prognosis in terms of CSS than those with a low RDW (p = 0.0003). On the other hand, univariate analysis demonstrated that pStage (p = 0.0008) was the only significant risk factor for a poor prognosis in elderly patients. CONCLUSIONS: We confirmed that a high RDW was significantly associated with the CSS of esophageal cancer patients after curative esophagectomy. Furthermore, in non-elderly patients, a high RDW was a significant and independent predictor of poor survival.

Prognostic value of preoperative inflammatory response biomarkers in patients with esophageal cancer who undergo a curative thoracoscopic esophagectomy.

BACKGROUND: Several inflammatory response biomarkers, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to predict survival in various cancers. The aim of this study is to evaluate the clinical value of these biomarkers in patients undergoing curative resection for esophageal cancer. METHODS: The LMR, NLR and PLR were calculated in 147 consecutive patients who underwent esophagectomy between January 2006 and February 2015. We examined the prognostic significance of the LMR, NLR, and PLR in both elderly and non-elderly patients. We evaluated the cancer-specific survival (CSS), with the cause of death determined from the case notes or computerized records. RESULTS: Univariate analyses demonstrated that TNM pStage (p < 0.0001), tumor size (p = 0.0014), operation time (p = 0.0209), low LMR (p = 0.0008), and high PLR (p = 0.0232) were significant risk factors for poor prognosis. Meanwhile, TNM pStage (p < 0.0001) and low LMR (p = 0.0129) were found to be independently associated with poor prognosis via multivariate analysis. In non-elderly patients, univariate analyses demonstrated that TNM pStage (p < 0.0001), tumor size (p = 0.0001), operation time (p = 0.0374), LMR (p < 0.0001), and PLR (p = 0.0189) were significantly associated with a poorer prognosis. Multivariate analysis demonstrated that TNM pStage (p = 0.001) and LMR (p = 0.0007) were independent risk factors for a poorer prognosis. In elderly patients, univariate analysis demonstrated that that TNM pStage (p = 0.0023) was the only significant risk factor for a poor prognosis. CONCLUSIONS: LMR was associated with cancer-specific survival (CSS) of esophageal cancer patients after curative esophagectomy. In particular, a low LMR was a significant and independent predictor of poor survival in non-elderly patients. The LMR was convenient, cost effective, and readily available, and could thus act as markers of survival in esophageal cancer.

Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma.

BACKGROUND & AIMS: The roles of alternatively activated (M2) macrophages on pro-tumour phenotypes have been well documented in many cancers except hepatocellular carcinoma (HCC). Considering their close relationship with chronic tissue injuries as well as enhanced tumour invasiveness and growth, we aimed to investigate the direct effects of M2 macrophages on HCC. METHODS: M2 macrophages in 95 HCC clinical specimens were quantified using immunohistochemistry and quantitative PCR. The pro-tumour functions and the underlying molecular mechanisms of M2 macrophages in HCC were investigated in vivo and in an in vitro co-culture system. RESULTS: In the clinical study, high M2-specific CD163 (hazard ratio=2.693; p=0.043) and scavenger receptor A (hazard ratio=3.563; p=0.044) levels indicated poor prognosis and correlated with increased tumour nodules and venous infiltration in HCC patients. In an orthotopic model, the liver tumour volume was increased 3.26-fold (1.27 cm3±0.36) after M2 macrophage injection compared with the control (0.39 cm3±0.05) (p=0.032). An increased rate of lung metastasis was also found in the treatment group. In vitro, co-cultivation with M2 macrophages elevated the number of HCC cells (MHCC97L) and migration events by 1.3-fold and 3.2-fold, respectively (p<0.05). Strongly induced by MHCC97L, M2 macrophage-derived CCL22 was proven to enhance tumour migration capacities and correlate with venous infiltration in HCC patients. Increased epithelial-mesenchymal transition (EMT) via Snail activation in MHCC97L was found to be promoted by M2 macrophages and CCL22. CONCLUSIONS: M2 macrophages contribute to poor prognosis in HCC and promote tumour invasiveness through CCL22-induced EMT.