Multivariate Cox Survival Analysis Research Articles

Protein succinylation associated with the progress of hepatocellular carcinoma.

Although post-translational modification is critical to tumorigenesis, how succinylation modification of lysine sites influences hepatocellular carcinoma (HCC) remains obscure. 90 tumours and paired adjacent normal tissue of liver cancer were enrolled for succinylation staining. 423 HCC samples with 20 genes related to succinylation modification from TCGA were downloaded for model construction. Statistical methods were employed to analyse the data, including the Non-Negative Matrix Factorization (NMF) algorithm, t-Distributed Stochastic Neighbour Embedding (t-SNE) algorithm, and Cox regression analysis. The staining pan-succinyllysine antibody staining indicated that tumour tissues had a higher succinyllysine level than adjacent tissues (p < 0.001), which could be associated with a worse prognosis (p=0.02). The survival was associated with pathological stage, tumour recurrence status and succinyllysine intensity in the univariate or multivariable cox survival analysis model. The risk model from 20 succinyllysine-related genes had the best prognosis prediction. The high expression of succinylation modification in HCC contributed to the worse patient survival prognosis. Model construction of 20 genes related to succinylation modification (MEAF6, OXCT1, SIRT2, CREBBP, KAT5, SIRT4, SIRT6, SIRT7, CPT1A, GLYATL1, SDHA, SDHB, SDHC, SDHD, SIRT1, SIRT3, SIRT5, SUCLA2, SUCLG1 and SUCLG2) could be reliable in predicting prognosis in HCC.

A novel clinical and cardiac magnetic resonance risk score for early risk prediction after ST-segment elevation myocardial infarction

Abstract Background Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. However, predictive models including clinical and CMR variables are scarce and not routinely implemented in clinical practice. Purpose We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients. Methods We performed a multicenter prospective registry in three Spanish university hospitals of reperfused STEMI patients (n=1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failure (HF), whichever occurred first. Univariate and multivariate analyses were performed and a risk score was computed using the variables which independently predicted the risk of MACE. Results During a median follow-up of 5.52 [2.63–7.44] years, 216 first MACE (58 CV deaths, 71 NF-MI and 87 HF) were registered. Mean age was 59.3±12.3 years and most patients (82.8%) were male. Based on the four variables independently associated with MACE, we computed an 8-point risk score: time to reperfusion >4.15h (1 point), GRACE risk score >155 (3 points), CMR-LVEF <40% (3 points), and MVO >1.5 segments (1 point). This score permitted MACE risk stratification: MACE per 100 person-years was 1.96 in the low-risk category (0–2 points), 5.44 in the intermediate-risk category (3–5 points), and 19.7 in the high-risk category (6–8 points): p<0.001 in multivariable Cox survival analysis. Conclusions A novel risk score including clinical (time to reperfusion >4.15h and GRACE risk score >155) and CMR (LVEF <40% and MVO >1.5 segments) variables allows for simple and straightforward MACE risk stratification early after STEMI. External validation should confirm the applicability of the risk score. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) and Sociedad Española de Cardiología.

FDG PET and CT radiomics in diagnosis and prognosis of non-small-cell lung cancer.

18F-FDG PET and CT radiomics has been the object of a wide research for over 20 years but its contribution to clinical practice remains not yet well established. We have investigated its impact versus that of only histo-clinical data, for the routine management of non-small-cell lung cancer (NSCLC). Our patients were retrospectively considered. They all had a FDG PET-CT and immuno-histo-chemistry (IHC) to assess PD-L1 expression at the beginning of the disease. A prognosis univariate and multivariate Cox survival analyses was performed for overall survival (OS) and progression free survival (PFS) prediction, including a training/testing procedure. Two sets of 47 PET and 47 CT radiomics features (RFs) were extracted. Difference between RFs according to PD-L1 expression, the histology status and the stage level were tested using suited non parametric statistical tests and the receiver operating characteristics (ROC) curve and the area under curve (AUC). From 2017 to 2019, 212 NSCLC patients treated in our institution were included. The main conventional prognostic variables were stage and gender with a low added prognostic value in the models including PET and CT RFs. Neither PET nor CT RFs were significant to separate the different levels of PD-L1 expression. Several RFs differ between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumours and a large number of PET and CT RFs are significantly linked to patient stage. In our population, PET and CT RFs show their intrinsic power to predict survival but do not significantly improve OS and PFS prediction in the different multivariate models, in comparison to conventional data. It would seem necessary to carry out one's own survival analysis before determining a radiomics signature.

The imaging features and prognosis of gliomas involving the subventricular zone: An MRI study

Rationale and objectivesAs the largest concentrated region of neural stem cells in the adult brain, the subventricular zone (SVZ) is considered to have a close relationship with the origin of gliomas. An in-depth study of the characteristic manifestations associated with SVZ involvement in glioma may provide new ideas for individualized diagnosis and treatment of this fatal disease. Materials and methodsAll 279 patients with glioma who underwent surgical treatment in our department from January 2016 to December 2021 were included. Clinical and imaging data were collected, and telephonic follow-up was conducted to analyze the overall survival and progression-free survival. Prognostic factors including SVZ involvement on glioblastoma patients’ survival were analyzed. Next, the relationship between SVZ involvement, a set of unique imaging features and gene status were determined respectively. The chi-squared test, logistics regression, and Cox regression were used for statistical analysis. ResultsThe patients were divided into the SVZ involvement group (n = 198, 70.97 %) and SVZ non-involvement group (n = 81, 29.03 %). The median overall survival and progression-free survival were 13 months and 7 months for the SVZ involvement group, but 25 months and 17 months for the SVZ non-involvement group, respectively. In multivariate Cox survival analysis, MRI SVZ involvement proved an independent risk factor for the survival of patients with glioblastoma. The patients with SVZ involvement sign had a lower rate of cystic lesion (32.32 % vs. 48.48 %, p = 0.029), and a larger mean maximum diameter (5.88 ± 1.28 vs. 3.28 ± 1.65 cm). Compared with high grade gliomas (HGG), T1 enhancement (25.25 % vs. 10.42 %, p = 0.041) and homogeneous signal on T2WI (14.14 % vs. 43.75 %, p = 0.025) were independently associated with SVZ involvement in WHO grade 2 gliomas(LGG). In the gene status analysis, the SVZ involvement group showed the lower rate of MGMT promoter methylation (57.58 % vs. 79.17 %, p = 0.017). ConclusionSVZ involvement in MRI at diagnosis is an independent negative prognostic indicator for the survival of glioblastoma patients. Some image signs are associated with SVZ involvement in HGG and LGG respectively. The unique imaging and gene features of gliomas with SVZ involvement indicate that this kind of tumor maybe a unique subgroup of gliomas.

Sex-specific comparison of clinical characteristics and prognosis in Crohn's disease: A retrospective cohort study of 611 patients in China.

Background: Real-world data on the impact of sex on the disease progression and prognosis of Crohn’s disease (CD) from large-scale Chinese cohorts are lacking. Aims: This study aimed to evaluate sex disparities in the clinical characteristics of, disease progression behaviours of and surgery-related risk factors for CD. Methods: A retrospective cohort study comprising 611 patients consecutively diagnosed with CD at Peking Union Medical College Hospital from January 2000 to December 2020 was conducted. Multivariate Cox regression and survival analyses was performed to assess the risk factors for disease progression and CD-related surgery in sex subgroups. Results: Male sex was an independent protective factor against multisystemic extraintestinal manifestations [EIMs] (HR: 0.52, p = 0.03) and a risk factor for intestinal perforation (HR: 1.85, p = 0.01). Male patients had longer EIM-free survival (p = 0.024) and shorter intestinal perforation-free survival (PFS) than females (p = 0.012). Of the 397 patients with the A2 classification, male patients had a higher risk of CD-related surgery (HR: 1.80, p = 0.028) and shorter surgery-free survival (SFS) than female patients (p = 0.04). Conclusion: Sex disparities in disease progression and outcomes of CD were revealed in a single Chinese centre. Male sex was independently associated with worse disease progression and prognosis including multisystemic EIMs and perforation, which suggests the need for individualized management according to risk classification.

Maternal anemia and long-term respiratory morbidity of the offspring-Results of a population-based cohort.

To evaluate the association between prenatal maternal anemia (hemoglobin, Hb < 11g/dl) and long-term respiratory morbidity of the offspring. A retrospective population-based cohort analysis was performed at a single tertiary medical center. We include all singletons born between 1991-2014 and discharged alive. Offspring with congenital malformations were excluded. The 3 study groups were defined on maternal Hb levels on discharge: severe anemia (< 7.0g/dl), mild to moderate anemia (7.0-11.0g/dl) and unexposed (≥ 11.0g/dl). Offspring respiratory morbidity was predefined on ICD-9 codes and recruited from the hospitalized medical records. A Kaplan-Meier survival curve was formed to compare the cumulative hospitalization and a multivariable Cox survival analysis was used to control for cofounders (gestational age, maternal age, diabetes, hypertensive disorders, post-partum hemorrhage and transfusion of blood products). 214,305 deliveries met the inclusion criteria: 807 (0.3%) mothers had severe anemia, 105,196 (49.1%) mothers had mild-moderate anemia, and the remaining were not anemic (108,302, 50.5%). Respiratory hospitalization was significantly higher among the offspring born to anemic mothers (6.2%; 5.3% and 5.1%; p = 0.020, in the study groups). However, association between maternal anemia and respiratory-related hospitalization remained significant only among the mild-moderate anemic group (adjusted Cox hazard ratio = 1.1; 95% CI 1.05-1.14; p < 0.01). The Kaplan-Meier survival analysis showed significant higher total respiratory hospitalizations in offspring according to maternal anemia status (Log Rank p-value = < .001). Maternal anemia was associated with long-term respiratory morbidity of the offspring.

Regional Variation in Access to Oncologic Care and Racial Disparities Among Cervical Cancer Patients.

The goal of this study was to determine whether access to gynecologic oncologists is correlated with disparate outcomes among cervical cancer patients, especially among Black women. An ecological study was performed using the National Cancer Database among stage I-IVA cervical cancer patients from 2004 to 2014. Data from the National Cancer Institute, the Society of Gynecologic Oncology, and the United States Census were compiled to describe access to care by region. Factors associated with receipt of optimal treatment (defined as surgery and/or radiation for stage IA-IB1 and IIA1; radiation and chemotherapy for stage IB2, IIA2, IIB-IVA or node positive disease) were identified using multivariate logistic regressions stratified by region, controlling for confounding factors including the number of gynecologic oncologists per states in each subregion. Cox multivariate survival analyses stratified by region were also performed. Of 42,213 women, 17.0% were Black. On multivariate analysis controlling for confounders, all Southern women were less likely to receive optimal treatment (adjusted odds ratio [aOR]: 0.80, 95% confidence interval [95% CI]: 0.75-0.85, P <0.001) compared with Northeastern women. Black women in the South (aOR: 0.76, 95% CI: 0.70-0.83, P <0.001) and Midwest (aOR: 0.78, 95% CI: 0.68-0.90, P <0.001) were less likely to receive optimal treatment compared with non-Black women in those regions. Black women in the South (adjusted hazard ratio [aHR]: 1.11, 95% CI: 1.04-1.18, P <0.001) and West (aHR: 1.34, 95% CI: 1.11-1.62, P =0.002) had worse mortality compared with non-Black women in those regions, despite controlling for access to gynecologic oncologists. The South, Midwest, and West had proportionally fewer cancer centers and gynecologic oncologists compared with the Northeast. Southern women are at risk of inadequate treatment for cervical cancer, and Black Southern women are at even higher risk of inadequate treatment and worse overall survival despite controlling for access to gynecologic oncologists. Social determinants of health and other barriers besides access to oncologists likely contribute to observed regional and racial disparities among cervical cancer patients.

FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis

To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance. The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05). FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.

Prognostic role of multiple abnormal genes in non-small-cell lung cancer.

BACKGROUNDNon-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years, the prognosis remains poor. Therefore, it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIMTo explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODSWe used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed.RESULTSAnalysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival: TP53 (P = 0.79), PTEN (P = 0.94), RB1 (P = 0.49), CTNNB1 (P = 0.24), STK11 (P = 0.32), and PIK3CA (P = 0.013). However, the probability of multiple genes (TP53, PTEN, RB1, and STK11) affecting survival was 0.025. Retrospective analysis of clinical data revealed that sex (hazard ratio [HR] = 1.29; [95%CI: 0.64-2.62]), age (HR = 1.05; [95%CI: 1.02-1.07]), smoking status (HR = 2.26; [95%CI: 1.16-4.39]), tumor histology (HR = 0.58; [95%CI: 0.30-1.11]), cancer stage (HR = 16.63; [95%CI: 4.8-57.63]), epidermal growth factor receptor (EGFR) mutation (HR = 1.82; [95%CI: 1.05-3.16]), abundance (HR = 4.95; [95%CI: 0.78-31.36]), and treatment with tyrosine kinase inhibitors (TKIs) (HR = 0.58; [95%CI: 0.43-0.78]) affected patient survival. Co-occurring mutations of TP53, PTEN, RB1, and STK11 did not significantly affect the overall survival of patients receiving chemotherapy (P = 0.96) but significantly affected the overall survival of patients receiving TKIs (P = 0.045).CONCLUSIONCo-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Nomogram constructed by immunological and inflammatory indicators for predicting prognosis of patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy plus surgery.

ObjectivesAt present, esophageal squamous cell carcinoma (ESCC) patients accepting neoadjuvant chemoradiotherapy (nCRT) plus surgery lack corresponding prognostic indicators. This study aimed to construct a prognostic prediction model for ESCC patients undergoing nCRT and surgery based on immune and inflammation-related indicators.MethodsWe retrospectively analyzed the levels of serum immune- and inflammation-related indicators of ESCC patients before receiving nCRT plus surgery in the training cohort (99 patients) and validation cohort (67 patients), which were collected from 2007 to 2020. Univariate and multivariate Cox survival analyses were conducted to evaluate the indicators to set up a nomogram associated with the patients’ overall survival (OS). The prediction accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), decision curve, calibration curve, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).ResultsUnivariate and multivariate Cox analyses demonstrated that immune globin A (IgA) and C-reactive protein (CRP) were independent risk factors. A nomogram based on IgA, CRP, and cTNM stage was established for predicted OS in the training cohort and validated in the validation cohort. The C-index of the nomogram was 0.820 (95% CI: 0.705–0.934), which was higher than that of the cTNM stage (0.655 (95% CI: 0.546–0.764), p < 0.05) in the training cohort, and similar results were observed in the validation cohort (0.832 (95% CI: 0.760–0.903 vs 0.635 (95% CI: 0.509–0.757), p < 0.001). Furthermore, the prediction accuracy and net benefit of the nomogram verified by the calibration curve, decision curve, NRI, and IDI were satisfactory in the training and validation cohorts.ConclusionThe newly constructed nomogram concluding serum IgA, CRP, and cTNM stage might be helpful in the prognosis prediction for ESCC patients receiving nCRT plus surgery.

Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS). We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3. We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19months (range: 12-51months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS. Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.

The Prognostic Value of Adjuvant Chemotherapy in Colon Cancer With Solitary Tumor Deposit.

PurposeThe aim of this study is to investigate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary tumor deposit (TD).MethodsThe primary study outcomes used in this study were colon cancer–specific survival (CSS) and overall survival (OS). The differences of the distribution of categorical variables in patients with colon cancer with the solitary TD according to adjuvant chemotherapy administration were tested using the Pearson’s chi-square test. The Kaplan–Meier method was utilized to evaluate CSS and OS. Hazard ratio (HR) and 95% confidence interval (CI) were calculated on the basis of Cox regression models to assess the prognostic value of different demographic and clinicopathological characteristics.ResultsA total of 877 patients with TanyN1cM0 colon cancer with solitary TD were identified in our analysis. It was found that OS (75.4% vs. 42.8% for 5-year OS rate, p < 0.001) and CSS (82.9% vs. 69.3% for 5-year CSS rate, p < 0.001) of patients with colon cancer with adjuvant chemotherapy administration were significantly better than those without adjuvant chemotherapy administration. Multivariate Cox survival analyses revealed that the overall and colon cancer–specific mortality risks of patients with adjuvant chemotherapy administration were decreased by 64.4% (HR = 0.356, 95% CI = 0.265–0.479, p < 0.001) and 57.4% (HR = 0.426, 95% CI = 0.286–0.634, p < 0.001) compared with those without adjuvant chemotherapy administration, respectively.ConclusionsAdjuvant chemotherapy administration could significantly improve OS and CSS in patients with colon cancer with the solitary TD. This is the first study to investigate and demonstrate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary TD.

A Prognostic Nomogram for Predicting Overall Survival in Pediatric Wilms Tumor Based on an Autophagy-related Gene Signature.

Wilms Tumor (WT) is the most common primary renal malignancy in children. Autophagy plays dual roles in the promotion and suppression of various cancers. The goal of our study was to develop a novel autophagy-related gene (ARG) prognostic nomogram for WT. The Cancer Genome Atlas (TCGA) database was used. We screened the expression profiles of ARGs in 136 WT patients. The differentially expressed prognostic ARGs were evaluated by multivariate Cox regression analysis and survival analysis. A novel prognostic nomogram based on the ARGs and clinical characteristics was established using multivariate Cox regression analysis. First, 69 differentially expressed ARGs were identified in WT patients. Then, multivariate Cox regression analysis was used to determine 4 key prognostic ARGs (CC3CL1, ERBB2, HIF-α and CXCR4) in WT. According to their ARG expression levels, the patients were clustered into high- and low-risk groups. Next, survival analysis indicated that high-risk patients had significantly poorer overall survival than low-risk patients. The results of functional enrichment analysis suggested that autophagy may play a tumor-suppressive role in the initiation of WT. Finally, a prognostic nomogram with a Harrell's concordance index (C-index) of 0.841 was used to predict the survival probability of WT patients by integrating clinical characteristics and the 4-ARG signature. The calibration curve indicated its excellent predictive performance. In summary, the ARG signature could be a promising biomarker for monitoring the outcomes of WT. We established a novel nomogram based on the ARG signature, which accurately predicts the overall survival of WT patients.

Clinical and Pathologic Characterization of 94 Radiation-Associated Sarcomas: Our Institutional Experience.

Radiation-associated sarcomas are an uncommon complication of therapeutic radiation. However, their prevalence has increased with the more widespread use of this treatment modality. The clinical, pathologic and genetic characteristics of radiation-associated sarcomas are not fully understood. In this study we describe the features of 94 radiation-associated sarcomas reviewed at our institution between 1993 and 2018, evaluate their overall survival (OS) and progression-free survival (PFS) outcomes, and compare them with their sporadic counterparts reviewed within the same time period. Histologic subtypes of all radiation-associated sarcomas included 31 (33%) undifferentiated sarcomas, 20 (21%) osteosarcomas, 17 (18%) angiosarcomas, 10 (11%) malignant peripheral nerve sheath tumor (MPNST), 9 (10%) leiomyosarcomas, 4 (4%) myxofibrosarcomas, and 3 (3%) rhabdomyosarcomas. Six patients had a documented cancer predisposition syndrome. The most common preceding neoplasms included adenocarcinoma (47%) and squamous cell carcinoma (19%), with a mean latency of 13 years. Multivariable Cox survival analysis demonstrated that advanced stage at diagnosis based on pT category (AJCC eighth edition) and fragmented resection were associated with worse survival outcomes. In addition, there was a statistically significant difference in PFS between radiation-associated undifferentiated sarcomas and MPNST when compared to their sporadic counterparts using the Kaplan-Meier method and Log-rank analysis. Overall, our study shows that radiation-associated sarcomas comprise a wide clinico-pathologic spectrum of disease, with a tendency for aggressive clinical behavior. This study further delineates the understanding of these uncommon diseases. Future studies are necessary to better understand the genetic and epigenetic changes that drive the differences in behavior between these tumors and their sporadic counterparts, and to offer better treatment options.

The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors.

ObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.MethodsPathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.ResultsKaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P<0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P<0.05). The MTHFR C667T genotype (χ 2 = 7.987, P=0.018) and allele distribution (χ 2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 = 0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).ConclusionsThe Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.

Correlation of HBV DNA and Hepatitis B Surface Antigen Levels With Tumor Response, Liver Function and Immunological Indicators in Liver Cancer Patients With HBV Infection Undergoing PD-1 Inhibition Combinational Therapy.

BackgroundThus far, few studies have investigated the safety and efficacy of programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) antibodies in patients with hepatitis B virus (HBV)-related liver cancer.ObjectiveTo investigate the effect of combination therapy with programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) on HBV-related liver cancer.MethodsUntil January 31, 2022, liver cancer patients with hepatitis B surface antigen (HBsAg) or HBV DNA positivity, treated with PD-1 ICIs and TKIs combined with nucleoside analogs (NAs), were retrospectively reviewed. The correlation between the change in HBV DNA and HBsAg levels and tumor response was analyzed using the χ2 test. Cox univariate and multivariate survival analyses and Kaplan–Meier curves were used to identify and compare risk factors and overall survival (OS).ResultsA total of 48 patients were enrolled in the study, with an objective response rate (ORR) of 31.3%, a disease control rate (DCR) of 66.7%; the incidence of adverse events was mostly mild. A significant decrease in HBV DNA and HBsAg levels was observed at 12 and 24 weeks compared with the baseline (p < 0.05). Compared to patients with progressive disease (PD), patients with disease control showed a more significant decrease in HBV DNA and HBsAg levels at 12 and 24 weeks (p < 0.001). Eleven patients showed elevations in HBV DNA level and one of them showed HBV reactivation; however, the reactivation was not associated hepatitis. Moreover, eight patients showed elevation in HBsAg. Elevation in HBV DNA level was associated with poor tumor response (P=0.001, OR=18.643 [95% CI: 3.271–106.253]). Cox survival analysis suggested that HBV DNA increase (P=0.011, HR=4.816, 95% CI: 1.439–16.117) and HBsAg increase (P=0.022, HR=4.161, 95% CI: 1.224–16.144) were independent risk factors associated with survival time. Kaplan–Meier curves suggested that patients who exhibited an increase in HBV DNA (6.87 months vs undefined, log-rank test: p= 0.004) and HBsAg (8.07 months vs undefined, log-rank test: p= 0.004) levels had a shorter median survival time (MST). Patients without increased HBsAg showed better baseline liver function and routine blood tests (p<0.05) than patients with increased HBsAg. An increase in C-reactive protein (CRP) and interleukin-6 (IL-6), and a decrease in T lymphocytes, CD4+ T lymphocytes, and B lymphocytes at 1-week post-treatment associated with HBsAg well-controlled.ConclusionHBV-related liver cancer patients treated with combination therapy showed improved efficacy and safety profiles. Combination therapy has some effect on HBV infection, and a correlation between tumor response and antiviral efficacy was found. Elevation of HBV DNA and HBsAg levels may indicate poorer tumor response and survival time. Better baseline liver function and early immune activation may be associated with decline in HBsAg levels.

Incidence and risk factors for parastomal hernia with a permanent colostomy.

This study aims to explore the incidence and risk factors for permanent colostomy complicated with a parastomal hernia (PSH) after rectal cancer resection. This was a retrospective study of gastrointestinal surgery performed from January 2013 to December 2017 in patients with colorectal cancer treated at the Affiliated Hospital of Qingdao University. The relevant clinical variables of the patient were analyzed. Kaplan-Meier, univariate, and Cox multivariate analyses were used to evaluate the influencing factors and morbidity of PSH. Among the 211 patients, 65 developed PSH. The cumulative incidence reached 33.5% at 62 months. In the multivariate Cox survival analysis, the results showed that being a woman, aged ≥65 years, having a body mass index(BMI) ≥ 25 kg/m2 , diabetes, and Clavien-Dindo Grade III and IV complications were risk factors for the occurrence of PSH. In our study, the incidence of PSH increased annually and reached a maximum of 33.5% after 62 months. Among the patient-related factors, female sex, age ≥65 years, BMI ≥ 25 kg/m2 , diabetes, and postoperative Clavien-Dindo Grade III and IV complications were significantly associated with the development of PSH. Therefore, intervention measures to prevent patients with this risk factor are advisable.

A Panel of E2F Target Gene Signature Predicting the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma is one of the most malignant tumors, and the therapeutic effects of traditional treatments are poor. It is urgent to explore and identify new biomarkers and therapeutic targets to develop novel treatments which are individualized and effective. Three hallmarks, including E2F targets, G2M checkpoint and DNA repair, were collected by GSEA analysis. The panel of E2F-related gene signature consisted of five genes: HN1, KIF4A, CDCA3, CDCA8 and SSRP1. They had various mutation rates ranging from 0.8 to 5% in hepatocellular carcinoma, and patients with gene mutation had poorer prognosis. Among these genes, HN1 has the greatest mutation rate, and SSRP1 has the greatest impact on the model with a B (COX) value of 0.8842. Patients with higher expression of these genes had poorer prognosis. Kaplan-Meier curves in stratified survival analysis confirmed that patients with high risk scores had poor prognosis (p < 0.05). The results of univariate and multivariate COX survival analysis showed that risk score was closely related to the overall survival of patients with hepatocellular carcinoma. For clinical validation, we found that all the genes in the model were upregulated in hepatocellular carcinoma tissues compared to normal liver tissues, which was consistent with the previous results we obtained. Our study demonstrated that a panel of E2F target genes signature including five genes could predict the prognosis of hepatocellular carcinoma. This panel gene signature can facilitate the development of individualized and effective treatment for hepatocellular carcinoma.

Long noncoding RNA MALAT1 polymorphism predicts MACCEs in patients with myocardial infarction

BackgroundMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs.MethodWe enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan–Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs.ResultsAmong the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan–Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060–2.277, P = 0.024).ConclusionsThe MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.

Identification of Prognostic Genes in Hepatocellular Carcinoma.

BackgroundPrevious studies have demonstrated the important role of tumor stem cells (TSCs) in the development of hepatocellular carcinoma (HCC); however, TSC-related genetic markers have not been investigated.AimThe aim of the present study was to identify stem cell-related signature genes to predict the prognosis of HCC, using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.MethodsIn total, 423 liver HCC tissue samples, including 373 tumor and 50 adjacent normal tissue samples from TCGA, and 115 primary tumor and 52 adjacent non-tumor tissue samples from the GEO GSE76427 database, were used in the present study. The non-negative matrix factorization (NMF) algorithm, t-distributed stochastic neighbor embedding (t-SNE) algorithm and Cox regression analysis were combined for model construction and validation.ResultsOverall, six clusters were identified using the NMF and t-SNE algorithms with 470 stem cell-related genes. The results demonstrated that patients in cluster 5 had the worst prognosis. For multivariate Cox survival analysis, 15 genes with optimal lambda values were chosen and eight genes were incorporated into the final regression model using the optimal Akaike information criterion value. Validation of the risk model using the aforementioned eight signature genes demonstrated the models strong reliability and stable predictive performance.ConclusionThe results of the present study indicated that the eight-gene (Hes family BHLH transcription factor 5, KIT ligand, methyltransferase-like 3, proteasome 26S subunit non-ATPase 1, Ras-related protein Rab-10, treacle ribosome biogenesis factor 1, YTH N6-methyladenosine RNA binding protein 2 and Zinc Finger CCCH-Type Containing 13) signature constructed by the model may be reliable in predicting the prognosis of patients with HCC.