Independent Predictor Of Poor Prognosis Research Articles

Low REST Expression Indicates a Biomarker of Poor Prognosis in Patients with Renal Cell Carcinoma.

It was initially found that neural-restrictive silencer factor/repressor 1-silencing transcription factor (REST) is a transcriptional repressor of neuronal genes in nonneuronal cells. However, it is reported to be abundantly expressed in various types of aggressive cancer cells. In this study, we evaluated the expression patterns of REST in renal cell carcinoma and found that its expression is lower in tumor tissues compared to normal tissues. The chi-square test showed that the low REST expression was closely related to patients' clinicopathologic parameters, including the pathologic stage and survival status. ROC curve showed that REST had excellent clinical diagnostic prospect. In addition, patients with low REST expression had poor over survival (OS) and relapse-free survival (RFS). Univariate and multivariate Cox regression analysis confirmed that the low REST expression was an independent predictor of poor prognosis in renal cell carcinoma. Gene set enrichment analysis identified P53 pathway, reactive oxygen species pathway, glycolysis, DNA repair, cholesterol homeostasis, and MYC targets V2 enriched with low REST expression phenotype. These results suggested that REST may be a novel biomarker for the diagnosis and prognosis of renal cell carcinoma in clinical applications.

Prognostic effect of preoperative red cell distribution width on the survival of patients who have undergone surgery for non-small cell lung cancer.

Red cell distribution width (RDW) is a prognostic factor for various malignancies, including colorectal, breast and lung cancer. The effect of preoperative RDW on the prognosis of patients who have undergone surgery for non-small cell lung cancer (NSCLC) was investigated in the present study. This retrospective, single-institution study included consecutive patients who had undergone complete NSCLC resection between January 2006 and December 2013 at the Department of Thoracic Surgery of Kansai Medical University Hospital (Hirakata, Japan). The overall and recurrence-free survival rates were compared using univariate and multivariate Cox proportional hazard models. A stepwise backward elimination method with a probability level of 0.15 was performed to select the most powerful outcome predictor sets. A total of 338 cases with NSCLC were analyzed. Of these, 25 had high RDWs (≥50 fl) and 313 had low RDWs (<50 fl). The 5-year overall survival rates in patients with high and low RDWs were 0.40 [95% confidence interval (CI): 0.21-0.58] and 0.80 (95% CI: 0.76-0.84), respectively, and the recurrence-free survival rates were 0.48 (95% CI: 0.25-0.68) and 0.70 (95% CI: 0.64-0.75), respectively. High RDW was identified as an independent prognostic factor for overall survival [hazard ratio (HR)=2.29; 95% CI: 1.3-4.01; P=0.004) but not for recurrence-free survival (HR=1.70; 95% CI: 0.93-3.12; P=0.085) by univariate and multivariate analysis. A high preoperative RDW was an independent predictor of poor prognosis in patients who had undergone radical resection of NSCLC. Therefore, patients with high RDW should be carefully monitored postoperatively, regardless of the disease stage.

Prognostic Value of Combined Detection of Preoperative Albumin-to-Fibrinogen Ratio and Neutrophil-to-Lymphocyte Ratio in Operable Esophageal Squamous Cell Carcinoma Patients without Neoadjuvant Therapy.

BackgroundWe retrospectively analyzed the prognostic value of the albumin-to-fibrinogen ratio (AFR)–neutrophil-to-lymphocyte ratio (NLR) score, comprising preoperative AFR and NLR, in esophageal squamous cell carcinoma (ESCC) patients after radical resection.Patients and MethodsOverall, 215 patients were included. The optimal cutoff value was determined using the receiver operating characteristic (ROC) curve. Based on a low AFR (<12.06) and high NLR (≥1.78), the AFR–NLR score was classified as 2 (both hematological abnormalities present), 1 (one abnormality present), or 0 (both abnormalities absent). Kaplan–Meier curves, Cox regression, and predicted nomogram were used to evaluate the prognostic value of the score.ResultsThe prognostic value of the AFR–NLR score was better than that of AFR or NLR alone (P <0.05). Multivariate analysis showed that a high AFR–NLR score was an independent predictor of poor prognosis for overall survival (P <0.001). Additionally, in the nomogram including the AFR–NLR score, the net reclassification improvement index increased by 35.5% (P <0.001), and the integrated discrimination improvement index increased by 9.0% (P <0.001). The predictive accuracy of the established nomogram model was proved using Harrell’s concordance index (0.811, 95% confidence interval: 0.765–0.856) and calibration curve. Notably, the decision analysis curve showed that the nomogram had a higher net benefit within most of the threshold probability range, indicating better clinical applicability.ConclusionThe AFR–NLR score is a useful predictor of the prognosis of ESCC patients after radical resection, and the nomogram established on the basis of this score has a good prognostic value.

Annexin A10 Expression Is Associated With Poor Prognosis in Small Bowel Adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. ANXA10 could be a new prognostic biomarker for SBA.

Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets.

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.

Clinical manifestations and outcome of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody positive patients with interstitial lung disease.

To analyse the clinical features and risk factors of acute/subacute interstitial pneumonia (A/SIP) and death in patients with positive anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) and positive anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab). Interstitial lung disease (ILD) patients with anti-ARS+ or anti-MDA5+ were recruited. Their demographics, clinical manifestations, laboratory data were collected and they were followed up for 1 year. Risk factors of A/SIP and mortality were analysed. 71 patients with anti-ARS+ ILD and 31 patients with anti-MDA5+ ILD were included. Incidence of ulcerative rash, Gottron's sign, pulmonary infection and A/SIP in the anti-MDA5+ group were significantly higher than those in the anti-ARS+ group, Creatine kinase (CK), leukocyte count, and lymphocyte count were lower, the value of serum ferritin (SF) was higher, and 12-month cumulative survival rate was lower. Advanced age, anti-MDA5+ and low immunoglobulin G (IgG) level were independent predictors of A/SIP. The decreased PaO2 and elevated SF were independent predictors for poor prognosis in A/SIP patients. Compared to anti-ARS+ group, the anti-MDA5+ group was more prone to ulcerative rash, Gottron's sign and pulmonary infection. Patients with anti-MDA5+, advanced age and decreased values of IgG were more likely to have A/SIP, while patients with A/SIP had lower incidence of myositis and arthritis. Mortality of A/SIP patients increased with higher serum ferritin level.

Over-expression of CXCL2 is associated with poor prognosis in patients with ovarian cancer.

Background:In the present study, we aimed to detect the expression of CXCL2 in epithelial ovarian cancer (OC) and explore its clinical significance.Methods:TCGA (The Cancer Genome Atlas) database was adopted to assess the significance of CXCL2. Tissue microarray and immunohistochemical staining were used to detect the expression of CXCL2 in epithelial OC, and its correlation with clinicopathological features and prognosis was statistically analyzed.Results:CXCL2 was highly expressed in epithelial OC tissues compared with the adjacent tissues. Such up-regulation of CXCL2 was significantly correlated with tumor differentiation (P = .001), tumor stage (P = .01), tumor location (unilateral or bilateral) (P = .003), and metastasis (P = .003). Kaplan-Meier and Cox proportional hazards regression analyses showed that high expression of CXCL2 was not an independent predictor of poor prognosis in epithelial OC.Conclusions:Collectively, the high expression of CXCL2 might be related to the invasion and metastasis of epithelial OC.

Serum iron: a new predictor of adverse outcomes independently from serum hemoglobin levels in patients with acute decompensated heart failure

Iron is an essential trace element in the body. However, in heart failure (HF), iron is only recognized as the cause of anemia. Actually, iron itself affects myocardial exercise tolerance and cardiac function via mitochondrial function. Therefore, it is necessary to clarify the pathological significance of iron in acute HF, irrespective of concomitant anemia. We investigated the impact of serum iron level at discharge on the prognosis of 615 patients emergently admitted with acute decompensated HF (ADHF). Patients were divided into two groups according to the median level of serum iron (62 µg/dL). The endpoint was the composite outcome, which included all-cause mortality and readmission for HF. During the mean follow-up period of 32.1 months, there were 333 events. Kaplan–Meier analysis showed that the incidence of the composite outcome was significantly higher in the Low iron group (P < 0.0001). In the multivariate analysis adjusted with factors including hemoglobin and ferritin levels, low serum iron was an independent predictor for the composite outcome (hazard ratio, 1.500; 95% confidence interval, 1.128–1.976; P = 0.0044). Low serum iron was an independent predictor of poor prognosis in ADHF, irrespective of hemoglobin or ferritin level, providing a new concept that iron may play a role in the pathophysiology of ADHF via non-hematopoietic roles.

Podoplanin expression in cancer-associated fibroblasts predicts unfavorable prognosis in node-negative breast cancer patients with hormone receptor-positive/HER2 − negative subtype

Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an indicator for poor prognosis in patients with invasive breast carcinomas, but little is known about its clinical significance in node-negative breast cancer patients with hormone receptor (HR) + /HER2 - subtype, who are expected to have a favorable prognosis. Immunohistochemical analyses were performed on 169 resected specimens of node-negative invasive carcinoma of no special type with HR + /HER2 - subtype using antibodies for podoplanin. When more than 10% of CAFs showed immunoreactivity with podoplanin as strong as that of internal positive controls, the specimens were judged as podoplanin-positive. Podoplanin-positive status in CAFs was observed in 16.0% (27 of 169 cases) and it associated with high Ki67 labeling index (LI) (> 30%) (p = 0.03), higher stromal tumor-infiltrating lymphocytes (p < 0.001) and progesterone receptor-negative status (p = 0.045). Log-rank test showed that podoplanin-positive status in CAFs correlated with shorter disease-free survival (DFS) (p = 0.007) and disease-specific survival (DSS) (p < 0.001). Univariate analysis showed a significant correlation between shorter DFS and podoplanin-positive status in CAFs (hazard ratio [HR] = 3.380; p = 0.012), the presence of lymphatic invasion (HR = 5.621; p < 0.001), high Ki67 LI (HR = 5.217; p < 0.001), and histological grade III (HR = 3.748; p = 0.008). According to Cox multivariate analysis, podoplanin-positive status in CAFs had the most significant effect on shorter DSS (HR = 37.759; p = 0.003) followed by high Ki67LI (HR = 27.664; p = 0.007). Podoplanin expression in CAFs could be an independent predictor for poor prognosis in node-negative breast cancer patients with HR + /HER2 - subtype.

Splenic volume on computed tomography scans is associated with mortality in patients with sepsis

ObjectivesThe spleen is a key organ of the immune system. Asplenia has been reported to increase the risk of sepsis from overwhelming post-splenectomy infection. However, there are few reports on the association between splenic volume and mortality in patients with no history of splenectomy. This study focused on splenic volume of patients with sepsis and evaluated the association between splenic volume and mortality. MethodsWe retrospectively investigated 232 patients with sepsis. The splenic volume was calculated by using computed tomography scans obtained on admission. The patients were categorized into tertiles based on their splenic volume, and the relationship between splenic volume and mortality was evaluated. Odds ratio curves based on splenic volume were created to assess the continuous associations between splenic volume and outcome with a logistic regression model. ResultsThe patients with sepsis were divided into three groups according to the first (73.6cm3) and second (128.7cm3) tertile values of splenic volume. Kaplan–Meier estimation of the probability of the patients’ survival followed up to 28 days showed significant differences between the groups (p=0.03). The hazard ratio for 28-day mortality in the first tertile group was 3.46 (95% CI 1.3–10.2; p=0.01) as compared with patients in the third tertile group. Patients with smaller spleens had increased odds ratios for mortality in the logistic regression model. ConclusionsSplenic volume appeared to be an independent predictor of poor prognosis.

Hepatitis B Virus Reactivation Potential Risk Factors in Hepatocellular Carcinoma via Transcatheter Arterial Chemoembolization: A Retrospective Research.

Background To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research. Methods A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. Results HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥104 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases (24.3%, 17/70). Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group. Conclusion Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients.

Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer.

Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with β-catenin, CyclinD, and BCL2 expression in patients with GC. A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients' overall survival, some clinicopathological variables, and β-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high. Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan-Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of β-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients. This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker.

Role of Quantitative EEG and EEG Reactivity in Traumatic Brain Injury.

This study aimed to explore the effectiveness of quantitative electroencephalogram (EEG) and EEG reactivity (EEG-R) to predict the prognosis of patients with severe traumatic brain injury. This was a prospective observational study on severe traumatic brain injury. Quantitative EEG monitoring was performed for 8 to 12 hours within 14 days of onset. The EEG-R was tested during the monitoring period. We then followed patients for 3 months to determine their level of consciousness. The Glasgow Outcome Scale (GOS) score was used. The score 3, 4, 5 of GOS were defined good prognosis, and score 1 and 2 as poor prognosis. Univariate and multivariate analyses were employed to assess the association of predictors with poor prognosis. A total of 56 patients were included in the study. Thirty-two patients (57.1%) awoke (good prognosis) in 3 months after the onset. Twenty-four patients (42.9%) did not awake (poor prognosis), including 11 cases deaths. Univariate analysis showed that Glasgow coma scale (GCS) score, the amplitude-integrated EEG (aEEG), the relative band power (RBP), the relative alpha variability (RAV), the spectral entropy (SE), and EEG-R reached significant difference between the poor-prognosis and good-prognosis groups. However, age, gender, and pupillary light reflex did not correlate significantly with poor prognosis. Furthermore, multivariate logistic regression analysis showed that only RAV and EEG-R were significant independent predictors of poor prognosis, and the prognostic model containing these 2 variables yielded a predictive performance with an area under the curve of 0.882. Quantitative EEG and EEG-R may be used to assess the prognosis of patients with severe traumatic brain injury early. RAV and EEG-R were the good predictive indicators of poor prognosis.

Surgical Outcomes in Patients With Centrally Located Non-small Cell Lung Cancer.

Identification of prognostic factors is helpful in selecting optimal treatment for centrally-located non-small cell lung cancer (NSCLC). This study aimed to detect prognostic factors in patients with centrally-located NSCLC. NSCLCs in the hilar area requiring pneumonectomy or sleeve lobectomy for complete removal are defined as centrally-located NSCLCs. We retrospectively investigated the clinical courses of 45 patients with such lesions. Sleeve lobectomies were performed on 33 patients and pneumonectomies on 12. Three and five-year survival rates were 72% and 62%, respectively. Presence of comorbidities (p=0.013), severe symptoms (p=0.001), high white cell count (p=0.001), and pathological T3-4 stage (p=0.004) were identified as independent predictors of poor prognosis. Operative procedures did not correlate with outcomes (p=0.722). Presence of comorbidities, severe symptoms, high white cell counts, and pathological T stage are independent predictors of poor prognosis. These data can contribute in selecting appropriate treatments for such lesions.

Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Objective:Anoctamin 7 (ANO7) is a calcium2+-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence (P < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strong ANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- or postoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11 chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa.

A combination of portal vein stent insertion and endovascular iodine-125 seed-strip implantation, followed by transcatheter arterial chemoembolization with sorafenib for treatment of hepatocellular carcinoma-associated portal vein tumor thrombus.

PurposeThis study aimed to assess efficacy of portal vein stent (PVS) insertion and endovascular iodine-125 (125I) seed-strip implantation, followed by transcatheter arterial chemoembolization (TACE) with sorafenib (PVS-125I TACE-S) in patients with hepatocellular carcinoma (HCC)-associated type II or type III portal vein tumor thrombus (PVTT).Material and methodsA retrospective study was performed on 53 consecutive patients with HCC and type II or type III PVTT, from May 2014 to July 2018. Patients were divided into 2 groups, including group A with 28 patients treated with PVS-125I TACE-S, and group B with 25 patients treated with TACE-S. Primary end-point was overall survival (OS), while secondary endpoints were hepatic function and disease control rate (DCR). Albumin-bilirubin (ALBI) score approach was used for evaluating liver function. Cox regression analysis was applied to identify factors associated with treatment outcomes.ResultsNo pre-operative differences were found in ALBI scores between group A and group B (–2.57 ±0.42 vs. –2.61 ±0.38, p = 0.724), or in these scores at 1 month post-operatively (–2.62 ±0.46 vs. –2.20 ±0.59, p = 0.666). However, these scores were significantly different at 3 (–2.17 ±0.59 vs. –1.69 ±0.48, p = 0.007) and 6 (–2.28 ±1.23 vs. –1.47 ±0.31, p = 0.044) months post-operatively. In addition, group A exhibited higher DCR (71.4% vs. 44.0%, p = 0.043) after 6 months of treatment and extended OS duration (11.4 vs. 7.7 months, p = 0.007). A stratified analysis revealed that OS in patients with type II PVTT did not differ significantly (10.4 vs. 10.7 months, p = 0.689), but OS with type III varied significantly (11.5 vs. 7.5 months, p = 0.002). Multivariate analysis revealed that tumor size > 10 cm (p = 0.002) and multiple tumors (p = 0.022) were independent predictors for poor prognosis, whereas PVS-125I TACE-S was predictor for favorable patient’s prognosis (p = 0.040).ConclusionsPVS-125I TACE-S represents a potentially viable strategy for improving hepatic functionality, DCR, and OS in HCC with type III PVTT compared with TACE-S alone.

Cyclin-dependent kinase 7 (CDK7) is an emerging prognostic biomarker and therapeutic target in osteosarcoma.

Background:Overexpression of cyclin-dependent kinase 7 (CDK7) is a well-known pathogenic feature of various malignancies and a sign of a more dismal prognosis. As relatively little is known about CDK7 in osteosarcoma, we elected to evaluate its expression, prognostic value, and function.Methods:We began by analyzing the publicly available data sets on CDK7 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2). The correlation between patient tissue CDK7 expression and their clinicopathological features and prognosis was assessed via immunohistochemical staining of a unique tissue microarray constructed from osteosarcoma specimens. Furthermore, we analyzed CDK7 expression in osteosarcoma cell lines and tissues by Western blot. CDK7-specific siRNA and a highly-selective CDK7 inhibitor, BS-181, were applied to determine the function of CDK7 on osteosarcoma cell growth and proliferation. In addition, the effect of CDK7 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic CDK7 effects in an in vivo environment.Results:Our results demonstrate that higher CDK7 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells.Conclusion:This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.

Risk factors analysis of prognosis of adult acute severe myocarditis.

BACKGROUNDAdult severe myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock with a high hospital mortality rate.AIMTo analyze the risk factors affecting the short-term prognosis of adult acute severe myocarditis (ASM).METHODSAdult patients with ASM (ASM group, n = 218) and acute nonsevere myocarditis (ANSM group, n = 80) who came to our department from January 2014 to January 2020 were enrolled in this study. Patients with ASM were divided into the ASM survival group (n = 185) and ASM nonsurvival group (n = 33) according to the treatment results during hospitalization. The clinical symptoms, laboratory examinations, treatment methods, complications, and the relationship between the treatment results of the two groups were retrospectively compared and discussed. The risk factors for death in patients with severe myocarditis were analyzed by binary logistic regression. A follow-up to 5.5 years was conducted on patients in the ASM survival group and ANSM group after discharge, and the readmission rate and incidence rate of dilated cardiomyopathy were analyzed.RESULTSCompared with the ASM survival group, the ASM nonsurvival group had longer QRS complex, higher incidence of cardiogenic shock, higher serum creatinine (SCr, 235μmol/L vs 89 μmol/L, P < 0.05), higher sensitive cardiac troponin I (cTnI, 4.45 μg/L vs 1.66 μg/L, P < 0.05) and brain natriuretic peptide (BNP, 1756 pg/mL vs 401 pg/mL, P < 0.05). The binary logistic regression revealed that there were statistical differences between the two groups in SCr, cTnI, and BNP values (all P < 0.05). After discharging from the hospital, patients in the ASM group and ANSM group had no significant differences in the readmission rate and incidence rate of dilated cardiomyopathy.CONCLUSIONElevated SCr, cTnI, and BNP are independent predictors for poor prognosis in patients with ASM. The long-term prognosis of patients in the ASM survival group is good.

Circulating Exosomal CircMYC Is Associated with Recurrence and Bortezomib Resistance in Patients with Multiple Myeloma

Objective:Studies have shown that serum circRNA can be used as a biomarker for many tumors. However, the role of exosomal circRNA in prognostic evaluation in patients with multiple myeloma (MM) remains unclear. In this study, we aimed to analyze the role of circulating exosomal circMYC in the relapse and prognosis of patients with MM.Materials and Methods:Circulating exosomes from 122 patients with MM and 54 healthy people were isolated. Quantitative polymerase chain reaction was performed to measure circMYC exosomal expression. Kaplan-Meier survival curves with log-rank testing were used for estimating significance in survival rates. A Cox regression model was used for univariate and multivariate analysis.Results:Compared with healthy people, the expression level of serum exosomal circMYC was significantly increased in patients with MM. In addition, the expression of circMYC in circulating exosomes in bortezomib-resistant patients was significantly higher than that in non-resistant patients. The expression level of exosomal circMYC was correlated with deletion 17p, t(4;14), Durie-Salmon staging, and the International Staging System. Univariate and multivariate Cox regression analysis found that a high exosomal circMYC level was an independent predictor of poor prognosis in patients with MM. The patients with high exosome circMYC expression had higher relapse rates and higher mortality rates. The overall survival rate and progression-free survival rate of MM patients with high exosomal circMYC expression were lower than those of patients with low exosomal circMYC expression.Conclusion:These findings suggest that circulating exosomal circMYC has great potential as a biomarker for the diagnosis and prognosis of MM.

The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer.

SMARCA4 mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established. To characterize SMARCA4 alterations in NSCLC, we analyzed the genomic, protein expression, and clinical outcome data of patients with SMARCA4 alterations treated at Memorial Sloan Kettering. In 4,813 tumors from patients with NSCLC, we identified 8% (n = 407) of patients with SMARCA4-mutant lung cancer. We describe two categories of SMARCA4 mutations: class 1 mutations (truncating mutations, fusions, and homozygous deletion) and class 2 mutations (missense mutations). Protein expression loss was associated with class 1 mutation (81% vs. 0%, P < 0.001). Both classes of mutation co-occurred more frequently with KRAS, STK11, and KEAP1 mutations compared with SMARCA4 wild-type tumors (P < 0.001). In patients with metastatic NSCLC, SMARCA4 alterations were associated with shorter overall survival, with class 1 alterations associated with shortest survival times (P < 0.001). Conversely, we found that treatment with immune checkpoint inhibitors (ICI) was associated with improved outcomes in patients with SMARCA4-mutant tumors (P = 0.01), with class 1 mutations having the best response to ICIs (P = 0.027). SMARCA4 alterations can be divided into two clinically relevant genomic classes associated with differential protein expression as well as distinct prognostic and treatment implications. Both classes co-occur with KEAP1, STK11, and KRAS mutations, but individually represent independent predictors of poor prognosis. Despite association with poor outcomes, SMARCA4-mutant lung cancers may be more sensitive to immunotherapy.