Survival Prognosis Of Patients Research Articles

Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma.

Simple SummaryColorectal cancer (CRC) belongs to the most common cancer types. It is well known that half of all CRC possess missense mutations in the TP53 tumor suppressor gene. However, the entire signaling cascade upstream and downstream of the p53 protein may also contribute to CRC development, if relevant players in this signaling cascade lost their function. Besides p53 loss-of-function by mutations, epigenetic changes (DNA methylation, post translational modifications of histones, micro-RNAs) play a vital role in CRC development. In the present review, we concentrated on the epigenetic modifications related to the entire p53 signal transduction cascade upstream and downstream of p53. Indeed, numerous epigenetic aberrations influence the tumor suppressor function of p53 independent of missense mutations. Thus, the role of p53 for CRC development, therapy response and survival prognosis of patients may be much more complex than predicted earlier. Hence, we are in need to use novel diagnostic methods that are capable of evaluating the genetic and epigenetic changes in the “p53 signalome”, so that diagnosis and management of CRC will improve.Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the TP53 tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of APC and MGMT was associated with increased mutation rates of TP53. The micro-RNA 34a activates TP53 and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if TP53 is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the “p53 signalome” have the potential to improve the predictive and prognostic power in CRC diagnostics and management.

Clinical observation of surgical resection combined radiofrequency in patients with CNLC Ⅱa~Ⅲa stage multiple hepatocellular carcinoma

Objective: To investigate the effects of four therapeutic methods in the comprehensive treatment of China liver cancer staging (CNLC)Ⅱa~Ⅲa stage multiple hepatocellular carcinoma. Method: A retrospective study was conducted to collect clinical data of patients with multiple hepatocellular carcinoma (CNLC stage Ⅱa-Ⅲa), who received transhepatic arterial chemoembolization (TACE group, 73 cases), radiofrequency ablation (RFA group, 70 cases), TACE combined RFA (TACE combined RFA group, 69 cases) and surgical resection combined RFA (surgical resection combined RFA group, 57 cases) in the First Hospital of Lanzhou University from January 11, 2010 to January 31, 2017. The general data of age, gender, primary tumor, and laboratory examination were collected. The differences in overall survival rates and the survival rates among stratified subgrouping with different clinical factors between the four groups of patients were compared by the Kaplan-Meier method. Cox proportional hazards regression model analyzed the prognostic factors. Result: A total of 269 patients were enrolled and there were 194 males and 59 females with a median age of 58 years ranging from 23 to 84. The TACE group's 1, 3, and 5-year survival rates were 43.5%, 10.2%, and 0, respectively. The RFA group were 46.3%, 17.7%, and 0, respectively. The TACE combined RFA group were 56.8%, 21.5%, and 2.3%, respectively. The surgical resection combined RFA group was 76.5%, 38.7%, and 3.8%, respectively. The surgical resection combined RFA group has the best outcome(P<0.05). Univariate analysis showed that surgery combined RFA, tumor diameter<5 cm, no vascular invasion, preoperative AFP≤400 μg/L and TB<34 μmol/L are protective factors to improve the survival prognosis of patients with CNLCⅡa~Ⅲa stage multiple hepatocellular carcinoma(HR=0.784,0.718,0.633,0.846,0.617;all P<0.05). Multivariate Cox analysis showed that surgery combined RFA, tumor diameter<5 cm, preoperative AFP≤400 μg/L were independent risk prognostic factors for CNLCⅡa-Ⅲa stage multiple hepatocellular carcinoma (HR=0.702,0.743,0.647;all P<0.05). Conclusions: Surgical resection combined RFA is an effective method for the treatment of stage Ⅱa-Ⅲa hepatocellular carcinoma. Surgical resection combined RFA has more advantages in treatment patients with complicated hepatocellular carcinoma whose diameter<5 cm, tumor number<3, and preoperative AFP≤400 μg/L. Surgical resection combined RFA, tumor diameter<5 cm, preoperative AFP≤400 μg/L are independent influencing factors for the survival prognosis of patients with complicated hepatocellular carcinoma.

Pretreatment Neutrophil-to-Lymphocyte Ratio: A Prognostic Biomarker of Survival in Patients With Epithelial Ovarian Cancer.

BackgroundInflammation is pathognomonic of all stages of tumor formation, and therefore, there is renewed interest in systemic inflammatory response (SIR) markers including haematological inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) as prognostic predictors in several cancers.AimThis study was aimed to investigate the effect of pretreatment peripheral blood NLR on the survival prognosis of patients with epithelial ovarian cancer (EOC).MethodsWe identified 93 patients with a complete clinical record from a cohort of 155 patients who received treatment for EOC between 2009 and 2018. Patients’ sociodemographic and clinicopathologic characteristics, and updated three-year follow-up status were extracted from medical records. Pretreatment peripheral blood NLR was calculated by dividing the neutrophil count by the lymphocyte count. We employed the receiver operating characteristic (ROC) curve to identify the optimal cut-off value of the NLR in estimating progression-free survival (PFS) and overall survival (OS). The PFS and OS were assessed using the Kaplan-Meier method, and survival differences were compared using the Log Rank (Mantel-Cox) test. Independent prognostic predictors were determined using Cox regression analysis.ResultsAccording to the ROC curves, the optimal cut-off values for the NLR were 2.23 and 1.93 for PFS and OS, respectively. A high NLR was associated with poor PFS (P = 0.033) and OS (P = 0.013) in the univariate analyses. In the multivariate analyses, a high NLR was still an independent predictor of OS (hazard ratio [HR] = 2.23; 95% CI, 1.08 to 4.61) but not PFS (hazard ratio [HR] = 2.43; 95% CI, 0.95 to 6.27).ConclusionThe NLR at an optimum cut-off value of 1.93 is an independent prognostic predictor of OS in patients with EOC.

Thrombosis And Thromboprophylaxis In COVID-19 Patients During Hospitalization And Early Post-discharge Period

While SARS-CoV-2 infection continues to circulate around the world, there are still many uncertainties on how to treat the patients with this potentially deadly virus, and more importantly, for how long!&#x0D; COVID-19 causes many different symptoms, among which coagulopathy seems to play an essential role in the survival prognosis of patients. While medical centers worldwide have developed various algorithms for preventing thrombosis in COVID-19 patients, there are still no clear guidelines on the length of thromboprophylaxis therapy, target groups who should receive suitable anticoagulant prophylaxis, and even the choice of the most appropriate agent for such treatment.&#x0D;

Value of Nomogram Incorporated Preoperative Tumor Volume and the Number of Postoperative Pathologically Lymph Node Metastasis Regions on Predicting the Prognosis of Thoracic Esophageal Squamous Cell Carcinoma.

BackgroundThe aim of this study was to explore the influence of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically lymph node metastasis (LNM) regions on survival prognosis of esophageal squamous cell carcinoma (ESCC) patients.MethodsA total of 296 patients with ESCC treated by standard curative esophagectomy were retrospectively analyzed. These patients were grouped for further analysis according to the optimal threshold of preoperative tumor volume, length, maximum diameter and the number of postoperative pathologically LNM regions. Kaplan–Meier method was used to calculate survival rate and survival comparison was performed by Log rank test. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Nomogram model was established by integrating statistically significant clinicopathological parameters, and the predictive value was further verified by calibration curve, concordance index (C-index) and decision curve.ResultsThe univariate and multivariate Cox regression analysis all showed that differentiation grade, TNM stage, adjuvant therapy, preoperative tumor volume and the number of post operative pathologically LNM regions were independent prognostic factors for PFS and OS (all P<0.05). The C-indexes of PFS and OS by nomograms were predicted to be 0.747 (95% CI: 0.717–0.777) and 0.732 (95% CI: 0.697–0.767), respectively, which were significantly higher than the 7th AJCC TNM stage, the C-indexes 0.612 (95% CI: 0.574–0.650) and 0.633 (95% CI: 0.595–0.671), separately. In addition, the calibration curves of nomogram models were highly consistent with actual observation for the five-year PFS and OS rate, and the decision curve analysis also showed that nomogram models had higher clinical application potentials than TNM staging model in predicting survival prognosis of thoracic ESCC after surgery.ConclusionThe nomograms incorporated preoperative tumor volume and the number of postoperative pathologically LNM areas are of great value in predicting survival prognosis of patients with thoracic ESCC.

Effects of prognostic nutrition index on side effects and prognosis of radiotherapy and chemotherapy after radical gastrectomy.

e16002 Background: To investigate the impact of preoperative prognostic nutritional index (PNI) on the severity of radiotherapy and chemotherapy toxicity and survival prognosis in patients with gastric cancer through retrospective analysis and research in order to guide clinical nutritional support treatment for patients with gastric cancer. Methods: Through a retrospective cohort study，we analyzed the data of 191 patients with gastric cancer in the Department of Gastrointestinal Surgery of the Affiliated Hospital of Guizhou Medical University and Guizhou Cancer Hospital from January 2008 to December 2018. According to the cut-off value, the patients were divided into high PNI group (PNI≥47.7) and low PNI group (PNI &lt; 47.7). We Compared the incidences of severe radiotherapy and chemotherapy toxicities and overall survival in high PNI group and low PNI group. and make Analysis of prognostic factors. Results: The low PNI group was more prone to severe radiochemotherapy hematological side effects than the high PNI group, and the postoperative survival time was shorter. Multivariate analysis showed that: TNM stage (P = 0.000) and PNI (P = 0.001) were Independent risk factors in predicting overall survival rate. Conclusions: The preoperative prognostic nutrition index is a useful factor for predicting the incidence of radiotherapy and chemotherapy toxicities in patients after gastric cancer surgery.It is one of the important factors affecting the prognosis of gastric cancer and helps to guide the nutritional support treatment of gastric cancer patients.

Correlation and Survival Analysis of Distant Metastasis Site and Prognosis in Patients With Hepatocellular Carcinoma.

PurposeTo investigate the prognostic factors and survival analysis of patients with hepatocellular carcinoma with distant metastasis.MethodsThe clinical data of 3,126 patients with distant metastasis of hepatocellular carcinoma from 2010 to 2015 were extracted from SEER database, and the correlation between the location of distant metastasis of hepatocellular carcinoma and prognosis was retrospectively analyzed. Patients were grouped according to different metastatic sites. The clinical characteristics of each group were compared by chi-square test, the survival curve was drawn by Kaplan-Meier method, Log-rank test was used for univariate analysis, and Cox regression for multivariate analysis. And use propensity score matching (PSM) to reduce differences in baseline characteristics.ResultsBefore PSM, the prognosis of patients with hepatocellular carcinoma with lung metastasis is worse than that of patients without lung metastasis. And there was no statistically significant difference with or without bone metastases.Patients with one type of organ metastasis had better prognosis than those with multiple organ metastasis. Among patients with organ metastasis, bone metastasis has a better prognosis than patients with lung metastasis. After PSM, patients with HCC with bone metastases had a worse prognosis than those without bone metastases (P<0.05). Univariate analysis showed that the degree of tumor differentiation, T stage, N stage, primary tumor and metastatic surgery, radiotherapy and chemotherapy, tumor size, single organ metastasis, the number of metastatic organs, and the combination of metastatic organs were related to the prognosis of patients with distant metastasis of hepatocellular carcinoma (P < 0.05). Multiariate analysis showed that age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor prognosis in patients with metastatic hepatocellular carcinoma.ConclusionThe lung is the most common site of distant metastasis of hepatocellular carcinoma. Single organ metastasis has better prognosis than multiple organ metastasis. Age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor overall survival and cancer-specific survival prognosis in patients with metastatic hepatocellular carcinoma.

Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature.

Glioblastomas (GBM)—the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.

Study on the expression of p62 protein in patients with lung adenocarcinoma

To explore the expression of p62 protein in lung adenocarcinoma (LUAD). In this study, a cross-sectional study was adopted. From December 2011 to May 2013, 60 patients with lung adenocarcinoma who were diagnosed and treated in Tongji Hospital of Tongji University, Shanghai were selected for paraffin embedding and tissue chip preparation, and immunohistochemistry (IHC) technology was used to detect the expression of p62 in lung adenocarcinoma patients' cancer tissues and adjacent tissues, and analyze the relationship between p62 expression and the clinicopathological characteristics and survival prognosis of patients with lung adenocarcinoma; at the same time, 6 cases of lung adenocarcinoma were selected by random sampling cancer tissues and adjacent tissues were detected by Western Blot (WB) to detect p62 protein and analyzed by gray value. Preoperative examination specimens of inpatients with lung adenocarcinoma diagnosed from April 2018 to early October 2019, and plasma specimens of healthy subjects were collected, and enzyme linked immunosorbent assay (ELISA) was used to detect lung adenocarcinoma patients and healthy patients. The expression of p62 in the plasma of the subjects was statistically analyzed using SPSS 22.0 software. The results of IHC showed that the positive expression rate of p62 in cancer tissues was significantly higher than that in adjacent tissues, and the difference was statistically significant (t=5.593, P<0.001). Similarly, WB results showed that the expression of p62 protein in cancer tissues was significantly higher than that in adjacent tissues. It is statistically relevant (t=2.238, P=0.049). The expression of p62 was statistically correlated with tumor size, clinicopathological stage and lymph node metastasis in patients with lung adenocarcinoma (all P<0.05). The overall survival of patients with lung adenocarcinoma with high p62 expression was worse than that of patients with low p62 expression (95%CI was 0.238-0.870, P=0.028), suggesting that the high expression of p62 is related to the poor prognosis of patients with lung adenocarcinoma. The level of p62 protein in the plasma of patients with lung adenocarcinoma was significantly higher than that in the healthy control group. The difference was statistically significant (t=8.533, P<0.001). The area under the receiver operating characteristic curve was 0.835 (95%CI was 0.779-0.891, P<0.001), which is significantly higher than CEA, CA125, CA153 and other single traditional indicators, and the combined detection of four indicators has the highest diagnostic efficiency. p62 was strongly expressed in cancer tissues and serum, which is related to the poor prognosis and overall survival rate of LUAD patients.

Serum β-klotho is a potential biomarker in the prediction of clinical outcomes among patients with NSCLC

BackgroundWe aimed to investigate the β-klotho (KLB) expression in non-small cell lung cancer (NSCLC) and to determine its value as a novel molecular target for survival prognosis in patients with NSCLC.MethodsThe serum KLB concentrations in 50 patients with NSCLC and the 20 healthy persons were measured by enzyme-linked immunosorbent assay (ELISA) methods. The relationship between serum KLB level, including the level change after therapy, and the progression-free survival (PFS) and overall survival (OS) were analyzed. The KLB expression in A549 cells was measured by real-time polymerase chain reaction (RT-PCR) and western blotting. The function of cells was revealed by in vitro studies.ResultsThe concentrations of serum KLB in patients with NSCLC were obviously lower than those in healthy subjects. KLB expression was significantly increased in patients after chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy. In addition, expression of KLB was positively related with PFS and OS. Compared with 16-human bronchial epithelial (HBE) cells, the expression level of KLB was significantly decreased in A549 cells. Overexpression of KLB suppressed the proliferation of A549 cells, along with G1-to-S phase arrest and apoptosis induction.ConclusionsKLB plays an anti-tumorigenic role in NSCLC. KLB may be a candidate target for the diagnosis and treatment of NSCLC and may serve a potentially significant role in future clinical applications.

Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns (not necessarily of Turing type), including pseudopalisades, can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related .

An mRNA characterization model predicting survival in patients with invasive breast cancer based on The Cancer Genome Atlas database.

Invasive breast cancer is a highly heterogeneous tumor, although there have been many prediction methods for invasive breast cancer risk prediction, the prediction effect is not satisfactory. There is an urgent need to develop a more accurate method to predict the prognosis of patients with invasive breast cancer. To identify potential mRNAs and construct risk prediction models for invasive breast cancer based on bioinformaticsMETHODS: In this study, we investigated the differences in mRNA expression profiles between invasive breast cancer and normal breast samples, and constructed a risk model for the prediction of prognosis of invasive breast cancer with univariate and multivariate Cox analyses. We constructed a risk model comprising 8 mRNAs (PAX7, ZIC2, APOA5, TP53AIP1,MYBPH, USP41, DACT2, and POU3F2) for the prediction of invasive breast cancer prognosis. We used the 8-mRNA risk prediction model to divide 1076 samples into high-risk groups and low-risk groups, the Kaplan-Meier curve showed that the high-risk group was closely related to the poor prognosis of overall survival in patients with invasive breast cancer. The receiver operating characteristic curve revealed an area under the curve of 0.773 for the 8 mRNA model at 3-year overall survival, indicating that this model showed good specificity and sensitivity for prediction of prognosis of invasive breast cancer. The study provides an effective bioinformatic analysis for the better understanding of the molecular pathogenesis and prognosis risk assessment of invasive breast cancer.

Nomograms to predict the prognosis in locally advanced oral squamous cell carcinoma after curative resection

BackgroundOral squamous cell carcinoma (OSCC) is the dominant histologic type of oral cancer. Locally advanced OSCC remains a major therapeutic challenge. Our study aimed to develop and validate nomograms predicting survival prognosis in patients with locally advanced oral squamous cell carcinoma (OSCC) after curative resection.MethodsA total of 269 consecutive patients with primary OSCC who received curative resection between September 2007 and March 2020 were retrospectively enrolled in our study. Patients were randomly assigned to the training cohort (n = 201) or the validation cohort (n = 68). Multivariate Cox regression analyses were conducted to determine independent prognostic factors for overall survival (OS) and cancer specific survival (CSS) in the training set, which were used to develop nomogram models estimating 3-, and 5-year OS and CSS. We also evaluated the nomograms using concordance indices (c-index), calibration curves, and decision curve analyses (DCA), and compared those with the AJCC 8th staging system. The results were externally validated in the validation cohort.ResultsAge, Kaplan-Feinstein (KFI) index, pT, the number of positive nodes and systemic inflammatory index (SII) were significant prognostic predictors for OS and CSS. The OS nomogram had c-index values of 0.712 in the training set and 0.697 in the validation set, while the CSS nomogram exhibited c-index values of 0.709 in the training set and 0.675 in the validation set. These data were superior to those of AJCC 8th staging system, suggesting high discriminative ability of the nomograms. Calibration curves exhibited good agreement between observed and predicted survival. DCA curves indicated the nomograms were with potential clinical usefulness. These results were validated in the validation set.ConclusionsThe novel nomograms incorporating clinically available characteristics for OS and CSS prediction were developed in the locally advanced OSCC patients after curative surgery. Validation revealed good discrimination and calibration, indicating the clinical utility of the nomograms in the individualized prognosis prediction of locally advanced OSCC after curative surgery.

Dynamic nomogram for long-term survival in patients with non-small cell lung cancer after pneumonectomy.

BackgroundThe study aims to identify prognostic factors of overall survival (OS) in patients who had pneumonectomy, in order to develop a practical dynamic nomogram model.MethodsA total of 2,255 patients with non-small cell lung cancer (NSCLC) who underwent pneumonectomy were identified from 2010–2015 in the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into a training (2011–2015) and a validation [2010] cohort. A nomogram and a risk classification system were constructed from the independent survival factors in multivariable analysis. The predictive accuracy of the nomogram was measured through internal and external validation.ResultsIndependent prognostic factors associated with OS were gender, age, pathology, tumor size, N stage, chemotherapy, and radiotherapy. The C-index of the nomogram for OS was 0.675 (95% CI: 0.655–0.694). Similarly, the AUC of the model was 0.733, 0.709, and 0.701 for the 1-, 3-, and 5-year OS, respectively. The calibration curves for survival demonstrated good agreement. Significant statistical differences were found in the OS of patients within different risk groups. An online calculation tool was established for clinical use.ConclusionsThis novel nomogram was able to provide a reliable prognosis for survival in patients with NSCLC undergoing pneumonectomy.

The Effect of the Prognostic Nutritional Index on the Toxic Side Effects of Radiochemotherapy and Prognosis After Radical Surgery for Gastric Cancer.

ObjectiveA retrospective analysis was conducted to investigate the effect of the preoperative prognostic nutritional index (PNI) on the severity of toxic side effects of radiochemotherapy and the survival prognosis of patients with gastric cancer to guide the clinical nutritional support for patients with gastric cancer.MethodsData of 191 patients with gastric cancer in the Department of Gastrointestinal Surgery of Guizhou Cancer Hospital and the Affiliated Hospital of Guizhou Medical University between January 2008 and December 2018 were analyzed retrospectively. Patients were allocated to the high PNI group (with PNI ≥47.7) and the low PNI group (with PNI <47.7) according to the PNI cutoff value, and the incidence of severe toxic side effects of radiochemotherapy and the overall survival time were compared between the high PNI group and low PNI group. In addition, prognostic factor analysis was performed.ResultsThe severe hematologic side effects of radiochemotherapy and shorter postoperative survival time were more likely to occur in the low PNI group than in the high PNI group. The multifactor analysis showed that TNM stage (p = 0.000) and PNI (p = 0.001) were the independent risk factors for the overall postoperative survival time in patients with gastric cancer.ConclusionPreoperative PNI might predict the severity of hematologic toxic side effects of adjuvant chemotherapy/radiochemotherapy in patients with gastric cancer after surgery. Patients in the low PNI group were more likely to have severe hematologic toxic side effects, and therefore a low PNI might be one of the important factors affecting the prognosis of gastric cancer.

Dual-layer detector spectral CT—a new supplementary method for preoperative evaluation of glioma

PurposeTo investigate the value of the iodine concentration (IC) measured by dual-layer detector spectral CT (DLDSCT) in evaluating the factors related to the treatment scheme and survival prognosis of patients with glioma. MethodsFrom 2018 to 2019, we prospectively collected the data of 99 patients with glioma. The degree of CT enhancement and the IC of low grade gliomas (LGGs, II), high grade gliomas (HGGs, III and IV), grade II and III gliomas, were compared. The predictive performance of the degree of CT enhancement and IC was examined via receiver operating characteristic (ROC) analysis. The correlations between IC and Ki-67 labeling index, isocitrate dehydrogenase (IDH) mutation, chromosome 1p/19q deletion status of the tumor were examined. ResultsBoth IC and the degree of CT enhancement of patients with HGG were significantly higher than those of patients with LGG (p < 0.001; χ2 =41.707, p < 0.001); IC had large area under the ROC curve for diagnostic HGG (0.931; 95 % CI: 0.882−0.979; p < 0.001). The IC in the grade III gliomas was significantly higher than that in grade II gliomas (p < 0.001); IC had a large area under the ROC curve for diagnostic grade III gliomas (0.865; 95 % CI: 0.779–0.952; p < 0.001). There was a significant positive correlation between IC and Ki-67 LI (r = 0.679; p < 0.001). ConclusionsThe DLDSCT technology can be used as a supplementary method to provide more information for preoperative grading of the gliomas and the prognosis assessment of the patients.

New insights for precision treatment of glioblastoma from analysis of single-cell lncRNA expression.

Glioblastoma (GBM) is a complex disease with high intratumoral heterogeneity, understanding the molecular characteristics of intratumoral heterogeneity accurately is the basis for precision treatment. Although the existing typing strategy based on tumor molecular characteristics has a positive effect, there is still room for improvement, which is mainly because the traditional typing is completed based on the sequencing data of tissue samples, that is, the obtained data are the average level of patient tumor tissues, masking the intratumoral heterogeneity of a single patient and cannot reflect the real level of patient tumor cells. At present, cancer molecular typing is mostly performed based on transcriptome (RNA-seq) without considering lncRNA molecules that are also tissue-specific and developmental stage-specific. Therefore, in this study, we used lncRNAs as typing markers and combined single-cell expression profiles to retype glioblastoma, providing new ideas for GBM molecular typing, and further analyzed the shortcomings of traditional therapies at the singlecell level based on typing results and proposed new precise therapeutic insights. We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing. The intratumoral heterogeneity of patients at the single-cell level was revealed using t-SNE, and the room for improvement of the existing traditional histotyping method was revealed using heat map and density curve. Subsequently, to validate the feasibility of lncRNA typing, we compared the similarities and differences of expression patterns between lncRNAs and mRNAs in GBM cells. Then, we used the R package "Seurat" to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs. For validation, we performed survival analysis on GBM tissue data from the TCGA database to reveal the impact of different subtypes on patient survival prognosis. Eventually, based on the results, we screened the therapeutic drugs of each subtype by targeting the downstream regulatory genes of lncRNAs and proposed a new precision therapeutic strategy. GBM has significant intratumoral heterogeneity at the single-cell level, with more than one traditional subtype highly expressed in each patient, which reflects the shortcomings of traditional histotyping. LncRNAs and mRNAs have similar expression patterns in GBM cells, and the expression coefficient of variation of lncRNAs is higher than that of mRNAs, meaning that lncRNAs will better reflect the intratumoral heterogeneity. GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics. Survival analysis showed that patients with different subtype compositions had different prognostic outcomes, so different subtypes had different effects on patient prognosis. Based on this, 47 drugs were screened for treatment. There are both shared and unique drugs between different subtypes. A new precision treatment strategy was proposed: for patients with different subtypes, in addition to the combination of drugs targeting single subtype, drugs targeting multiple subtypes can also be selected. Intratumoral heterogeneity may lead to poor prognosis or recurrence after treatment, and more precise typing of GBM can be performed based on single-cell lncRNA expression profiles. The biological characteristics possessed by different subtypes will have different effects on patients, such as survival time. For different subtypes, there are both drugs targeting single subtype and drugs targeting multiple subtypes, and we prefer drugs targeting multiple subtypes because this strategy can maximize medication efficiency and reduce the types of medication to reduce risks and side effects.

A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity

During the cancerous transformation of normal hepatocytes into hepatocellular carcinoma (HCC), the enzyme catalyzing the first rate-limiting step of glycolysis, namely the glucokinase (GCK), is replaced by the higher affinity isoenzyme, hexokinase 2 (HK2). Here, we show that in HCC tumors the highest expression level of HK2 is inversely correlated to GCK expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2− cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer

BackgroundThe complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration.MethodsThe differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman’s correlation coefficients and p-values.ResultsIn two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant.ConclusionThese findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.

High expression of Dll4 and CD44V6 is associated with clinicopathological characteristics and poor prognosis in osteosarcoma patients.

BackgroundOsteosarcoma is a malignant tumor with a poor prognosis. Dll4 and CD44V6 are involved in the regulation of tumor development. This study aims to analyze the expression of Dll4 and CD44V6 in osteosarcoma and the correlation with clinicopathological characteristics and prognosis.MethodsClinical data of 47 patients with osteosarcoma admitted to our hospital from April 2016 to May 2018 and confirmed by surgery or pathological examination were retrospectively analyzed. Osteochondroma and normal bone tissues from these cases were taken as controls. The protein levels of Dll4 and CD44V were detected by immunohistochemistry (IHC). The relationship between the expression of Dll4 and CD44V and the clinicopathological characteristics of patients with osteosarcoma was analyzed. An unconditional multi-factor logistic regression model was used to analyze the risk factors affecting the prognosis of patients with osteosarcoma.ResultsThe positive expression rates of Dll4 and CD44V6 in osteosarcoma were 85.11% (Dll4) and 91.49% (CD44V6), which were significantly higher than those in normal bone tissues of 18.52% (Dll4) and 7.41% (CD44V6), and in osteochondroma of 22.22% (Dll4) and 7.41% (CD44V6). The expression of CD44V6 and Dll4 were related to the Enneking stage and metastasis (P<0.05), and the expression of Dll4 was closely related to the degree of tumor differentiation (P<0.05). The 2-year survival rates of patients with Dll4 or CD44V6 positive expression were 25.00% and 21.88%, respectively, which were significantly lower than those with Dll4 or CD44V6 negative expression (85.71% and 93.33%) (P<0.05). The results of the unconditional multivariate logistic regression analysis showed that low tumor differentiation, high Enneking stage, metastasis, and positive expression of Dll4 and CD44V6 were risk factors affecting the mortality rate and prognosis of patients with osteosarcoma (P<0.05).ConclusionsThe positive expression rate of Dll4 and CD44V6 in osteosarcoma is high, and the expression level is closely related to the degree of tumor differentiation, Enneking stage, and metastasis. Dll4 and CD44V6 are risk factors affecting the survival prognosis for patients. Therefore, in clinical settings, the prognosis for patients could be evaluated by detecting the expression of Dll4 and CD44V6.