ZNF623 contributes to breast carcinoma progress by recruiting CtBP1 to regulate NF-κB pathway.

BACKGROUND: Breast cancer ranks among the most prevalent tumor types worldwide. Copy number amplification of chromosome 8q24 is frequently detected in breast cancer. ZNF623 is a relatively unexplored gene mapped to 8q24. Here, we explore the expression profile, prognostic significance, and biological action of ZNF623 in breast carcinogenesis. METHODS: To evaluate the mRNA expression pattern and prognostic relevance of ZNF623 across different cancer types, we conducted bioinformatic analyses. The expression of the gene was suppressed using ZNF623 shRNAs/siRNAs and augmented through transfection with plasmids containing ZNF623 cDNA. Cell viability assay, clonogenic assay, and transwell migration assay were utilized to assess the proliferation, viability, and invasion capacity of breast cancer cell lines. Luciferase reporter assay served as a pivotal tool to ascertain the transcriptional activity of ZNF623. IP-MS and co-IP were employed to validate that ZNF623 interacted with CtBP1. ChIP analysis and ChIP-qPCR were conducted to assess the genes targeted by ZNF623/CtBP1 complex. Flow cytometry was conducted to evaluate the phosphorylation status of p65. RESULTS: ZNF623 expression was notably elevated in breast cancer (BC). Prognostic analysis indicated higher expression of ZNF623 indicated worse survival. Functional experiments discovered that the upregulation of ZNF623 significantly enhanced both the proliferative and migratory capacities of breast cancer cells. Luciferase reporter assay indicated that ZNF623 was a transcription repressor. Immunoprecipitation coupled mass spectrometry analysis revealed a physical association between ZNF623 and CtBP1 in the interaction group. The conjoint analysis of ChIP-seq and TCGA DEG analysis revealed that the ZNF623/CtBP1 complex repressed a series of genes, such as negative regulation of the NF-kappaB signaling pathway. Flow cytometry analysis discovered that knockdown of ZNF623 decreased the phosphorylation level of p65, indicating that ZNF623 could regulate the activity of the NF-κB pathway. CONCLUSION: ZNF623 predicts poor prognosis of BC and enhances breast cancer growth and metastasis. By recruiting CtBP1, ZNF623 could suppress NF-κB inhibitors, including COMMD1, NFKBIL1, PYCARD, and BRMS1, expression from the transcription level.

Association between lactate/albumin ratio and prognosis in patients with acute myocardial infarction.

BACKGROUND: The association between the lactate/albumin ratio (L/A) as a diagnostic indicator and unfavourable clinical outcomes has been established in patients with community-acquired pneumonia, sepsis and heart failure, but the connection between L/A and all-cause mortality in patients with acute myocardial infarction (AMI) has yet to be fully understood. METHODS: This was a retrospective cohort study using MIMIC-IV (v2.2) data, with 2816 patients enrolled and all-cause mortality during hospitalization as the primary outcome. Kaplan-Meier (KM) analysis was used to compare the all-cause mortality between high-level and low-level L/A groups. Receiver operating characteristic (ROC) curve, Restricted cubic splines (RCS) and Cox proportional hazards analysis were performed to investigate the relationship between L/A ratio and in-hospital all-cause mortality. RESULTS: L/A values were significantly higher in the non-survivor groups than the survival groups (1.14 [.20] vs. .60 [.36], p < .05), and area under the ROC curve [.734 (95% confidence interval, .694-.775)] was better than other indicators. Data of COX regression analysis showed that higher L/A value supposed to be an independent risk factor for in-hospital mortality. RCS analysis showed evidence of an increasing trend and a non-linear relationship between L/A and in-hospital mortality (p-value was non-linear <.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (p < .001), and the former group had an increased risk of in-hospital mortality compared with the latter one (Log Rank p < .001). CONCLUSIONS: L/A demonstrates significant independent predictive power for elevated all-cause mortality during hospitalization in patients diagnosed with AMI.

Harnessing exosomes as cancer biomarkers in clinical oncology.

Exosomes are extracellular vesicles well known for facilitating cell-to-cell communication by distributing essential macromolecules like proteins, DNA, mRNA, lipids, and miRNA. These vesicles are abundant in fluids distributed throughout the body, including urine, blood, saliva, and even bile. They are important diagnostic tools for breast, lung, gastrointestinal cancers, etc. However, their application as cancer biomarkers has not yet been implemented in most parts of the world. In this review, we discuss how OMICs profiling of exosomes can be practiced by substituting traditional imaging or biopsy methods for cancer detection. Previous methods like extensive imaging and biopsy used for screening were expensive, mostly invasive, and could not easily provide early detection for various types of cancer. Exosomal biomarkers can be utilized for routine screening by simply collecting body fluids from the individual. We anticipate that the use of exosomes will be brought to light by the success of clinical trials investigating their potential to enhance cancer detection and treatment in the upcoming years.

Understanding m6A changes in chromophobe renal cell carcinoma and predicting patient outcomes survival.

N6-methyladenosine (m6A) is a prevalent mRNA modification known for its implications in various cancer types, yet its role in chromophobe renal cell carcinoma (chRCC) remains largely unexplored. In this study, we performed m6A-SEAL-seq and RNA-seq analyses on tissues from three chRCC subjects, aiming to uncover m6A alterations in chRCC. Our findings revealed reduced expression levels of four m6A regulators in chRCC tissues and highlighted differences in m6A levels compared to normal tissues. Furthermore, we identified specific genes and cancer-related pathways affected by these differences, including notable candidates like NOTCH1 and FGFR1, implicated in chRCC development. Additionally, we developed a predictive model based on the expression level of m6A associated genes, demonstrating promising prognostic capabilities for patient survival prediction. Overall, our study provides valuable insights into the role of m6A in chRCC and its potential as a prognostic indicator.

ST14 interacts with TMEFF1 and is a predictor of poor prognosis in ovarian cancer.

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

Impact of sarcopenia in elderly patients undergoing elective total hip arthroplasty on postoperative outcomes: a propensity score-matched study.

OBJECTIVE: Frailty poses a crucial risk for postoperative complications in the elderly, with sarcopenia being a key component. The impact of sarcopenia on postoperative outcomes after total hip arthroplasty (THA) is still unclear. This study investigated the potential link between sarcopenia and postoperative outcomes among elderly THA patients. METHODS: Totally 198 older patients were enrolled in this study. Sarcopenia in this group was determined by assessing the skeletal muscle index, which was measured using computed tomography at the 12th thoracic vertebra and analyzed semi-automatically with MATLAB R2020a. Propensity score matching (PSM) was employed to evaluate postoperative complications of grade II and above (POCIIs). RESULTS: The variables balanced using PSM contained age, sex and comorbidities including hypertension, diabetes, hyperlipidemia and COPD. Before PSM, sarcopenic patients with reduced BMI (24.02 ± 0.24 vs. 27.11 ± 0.66, P < 0.001) showed higher POCIIs rates (48.31% vs. 15%, P = 0.009) and more walking-assisted discharge instances (85.96% vs. 60%, P = 0.017) compared with non-sarcopenia patients. After PSM, this group maintained reduced BMI (23.47 ± 0.85 vs. 27.11 ± 0.66, P = 0.002), with increased POCIIs rates (54.41% vs. 15%, P = 0.002) and heightened reliance on walking assistance at discharge (86.96% vs. 60%, P = 0.008). CONCLUSION: Sarcopenia patients exhibited a higher incidence of POCIIs and poorer physical function at discharge. Sarcopenia could serve as a valuable prognostic indicator for elderly patients undergoing elective THA.

Prognostic Significance of Albumin-Globulin Ratio in Urachal Carcinoma.

INTRODUCTION: Although albumin-globulin ratio (AGR) has been used in the prognostic assessment of multiple solid malignancies, so far no research has confirmed the prognostic significance of AGR as a biomarker for urachal carcinoma. We analyzed the relationship between AGR and prognosis in urachal carcinoma, aiming to identify a promising prognostic biomarker for urachal carcinoma. METHODS: We reviewed the clinical data of 25 patients diagnosed with urachal carcinoma in the Xiangya Hospital, Central South University, from January 2008 to October 2021. The best cut-off value of preoperative AGR was determined according to the receiver operator characteristic curve. The Kaplan-Meier curve was used to analyze the effect of preoperative AGR on the overall survival (OS) and relapse-free survival (RFS) of patients. Cox proportional hazards model was used to analyze prognostic factors including preoperative AGR. RESULTS: The best cut-off value of preoperative AGR in urachal carcinoma patients is 1.45. Low preoperative AGR is significantly associated with worse OS and RFS. Univariate analysis and multivariate analysis indicated that low preoperative AGR is an independent and reliable factor to predict poor prognosis, OS, and RFS in urachal carcinoma patients. CONCLUSION: Urachal carcinoma patients with low preoperative AGR have worse prognosis, and preoperative AGR is a valuable prognostic indicator for urachal carcinoma research.

Increased SEC14L2 expression is associated with clinicopathological features and worse prognosis in oral squamous cell carcinoma.

Abnormal expression of SEC14L2 has been implicated in many human cancers. However, the role of SEC14L2 in oral squamous cell carcinoma (OSCC) remains unclear. Therefore, this study aimed to evaluate the expression and prognostic roles of SEC14L2 in OSCC. OSCC tumors and adjacent non-tumors were collected from OSCC patients and used for SEC14L2 mRNA expression by quantitative reverse transcription PCR (RT-qPCR). Additionally, the expression of SEC14L2 was further analyzed using The Cancer Genome Atlas-Head Neck Squamous Cell Carcinoma (TCGA-HNSCC) dataset to identify its relationship with HNSCC clinical characteristics. The Kaplan-Meier plot was used to assess survival rates, and the Tumor Immune Estimation Resource (TIMER) database was used to examine the correlation between SEC14L2 expression and tumor immune cell infiltration. In silico tools also looked at SEC14L2 involvement in cancer pathways through its protein network. The mRNA and protein levels of SEC14L2 are notably higher in both OSCC and HNSCC tissues compared to adjacent normal tissues. Upregulation of SEC14L2 was associated with advanced tumor stages, grades, metastasis, HPV-negative, and TP53 mutations in cancer patients. In addition, the high expression of SEC14L2 was negatively correlated with the poor survival of cancer patients and the infiltration of diverse immune cells in cancer patients. According to the findings of this investigation, SEC14L2 is significantly elevated in OSCC/HNSCC patients and associated with a worse prognosis. More investigation and clinical studies are required to completely understand the therapeutic potential of SEC14L2 in HNSCC and convert these findings into better patient outcomes.

Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells.

BACKGROUND: Tumor cells with the capability of radiation resistance can escape the fate of cell death after radiotherapy, serving as the main cause of treatment failure. Repopulation of tumors after radiotherapy is dominated by this group of residual cells, which greatly reduce the sensitivity of recurrent tumors to the therapy, resulting in poor clinical outcomes. Therefore, revealing the mechanism of radiation resistant cells participating in tumor repopulation is of vital importance for cancer patients to obtain a better prognosis. METHODS: Co-expressed genes were searched by using genetic data of radiation resistant cells (from GEO database) and TCGA colorectal cancer. Univariate and multivariate Cox regression analysis were performed to define the most significant co-expressed genes for establishing prognostic indicator. Logistic analysis, WGCNA analysis, and other types of tumors were included to verify the predictive ability of the indicator. RT-qPCR was carried out to test expression level of key genes in colorectal cancer cell lines. Colongenic assay was utilized to test the radio-sensitivity and repopulation ability of key gene knockdown cells. RESULTS: Prognostic indicator based on TCGA colorectal cancer patients containing four key radiation resistance genes (LGR5, KCNN4, TNS4, CENPH) was established. The indicator was shown to be significantly correlated with the prognosis of colorectal cancer patients undergoing radiotherapy, and also had an acceptable predictive effect in the other five types of cancer. RT-qPCR showed that expression level of key genes was basically consistent with the radiation resistance level of colorectal cancer cells. The clonogenic ability of all key gene knockdown cells decreased after radiation treatment compared with the control groups. CONCLUSIONS: Our data suggest that LGR5, KCNN4, TNS4 and CENPH are correlated with radiation sensitivity of colorectal cancer cells, and the indicator composed by them can reflect the prognosis of colorectal cancer patients undergoing radiation therapy. Our data provide an evidence of radiation resistant tumor cells involved in tumor repopulation, and give patients undergoing radiotherapy an approving prognostic indicator with regard to tumor progression.

A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer.

BACKGROUND: Although the incidence of late-onset colorectal cancer (LOCRC) has decreased, the incidence of early-onset colorectal cancer (EOCRC) is still rising dramatically. Heterogeneity in the genomic, biological, and clinicopathological characteristics between EOCRC and LOCRC has been revealed. Therefore, the previous prognostic models based on the total CRC patient population might not be suitable for EOCRC patients. Here, we constructed a prognostic classifier to enhance the precision of individualized treatment and management of EOCRC patients. METHODS: EOCRC expression data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The regulatory pathways were explored by gene set enrichment analysis (GSEA). The prognostic model was developed by univariate Cox-LASSO-multivariate Cox regression analyses of GEO samples. TCGA samples were used to verify the model. The expression and mutation profiles and immune landscape of the high-risk and low-risk cohorts were analyzed and compared. Finally, the expression and prognostic value of the model genes were verified by immunohistochemistry and qRT‒PCR analysis. RESULTS: The cell cycle was identified as the most significantly enriched oncological signature of EOCRC. Then, a 4-gene prognostic signature comprising MCM2, INHBA, CGREF1, and KLF9 was constructed. The risk score was an independent predictor of overall survival. The area under the curve values of the classifier for 1-, 3-, and 5-year survival were 0.856, 0.893, and 0.826, respectively, in the training set and 0.749, 0.858, and 0.865, respectively, in the validation set. Impaired DNA damage repair capability (p < 0.05) and frequent PIK3CA mutations (p < 0.05) were found in the high-risk cohort. CD8 T cells (p < 0.05), activated memory CD4 T cells (p < 0.01), and activated dendritic cells (p < 0.05) were clustered in the low-risk group. Finally, we verified the expression of MCM2, INHBA, CGREF1, and KLF9. Their prognostic value was closely related to age. CONCLUSION: In this study, a robust prognostic classifier for EOCRC was established and validated. The findings may provide a reference for individualized treatment and medical decision-making for patients with EOCRC.

Plasma thymidine kinase activity as a prognostic biomarker in pancreatic ductal adenocarcinoma: a single-center prospective study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) patients might benefit from a biomarker to more precisely prognosticate their overall survival to make more informed treatment and surveillance decisions. The aim of the study was to assess the circulating biomarker Thymidine kinase (TK) activity in samples from patients with PDAC to improve prognostic precision. MATERIAL AND METHODS: Using the sensitive TK activity (TKa) assay DiviTum®, serum samples from 60 PDAC patients were analyzed. RESULTS: Median TKa value for patients with PDAC was 931 Du/L. TK activity <931 and CA19-9 < 37 was prognostic for a longer survival, compared to patients with any or both TK activity >931 and CA19-9 > 37, with median 41.3 vs 8.6 months from sample to death (p < 0.001), and 3-year survival was 55.6% vs 8.9% (p < 0.001). Hazard ratio was 2.81 if any or both of TK or CA19-9 were above the cut-off value (p < 0.05).TKa in combination with CA19-9 outperforms each marker individually for prediction of survival. Overall survival is longer in patients with both TKa <931 Du/L and CA19-9 < 37. Further studies of TKa levels at different disease stages and correlation to outcome is warranted to find the full potential clinical usage of the TKa marker in PDAC.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department.

BACKGROUND: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). POPULATION AND METHOD: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. RESULT: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842-0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711-0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. CONCLUSION: NLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

Clinical significance of prognostic nutritional index (PNI)-monocyte-to-lymphocyte ratio (MLR)-platelet (PLT) score on postoperative outcomes in non-metastatic clear cell renal cell carcinoma.

BACKGROUND: Prognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). METHODS: In this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients' outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier estimate and Cox regression models. RESULTS: The mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P < 0.001) and MFS (P < 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients. CONCLUSIONS: Our data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC.

Prediction of response to preoperative neoadjuvant chemotherapy in extremity high-grade osteosarcoma using X-ray and multiparametric MRI radiomics.

PURPOSE: This study aims to evaluate the value of applying X-ray and magnetic resonance imaging (MRI) models based on radiomics feature to predict response of extremity high-grade osteosarcoma to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: A retrospective dataset was assembled involving 102 consecutive patients (training dataset, n = 72; validation dataset, n = 30) diagnosed with extremity high-grade osteosarcoma. The clinical features of age, gender, pathological type, lesion location, bone destruction type, size, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were evaluated. Imaging features were extracted from X-ray and multi-parametric MRI (T1-weighted, T2-weighted, and contrast-enhanced T1-weighted) data. Features were selected using a two-stage process comprising minimal-redundancy-maximum-relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression. Logistic regression (LR) modelling was then applied to establish models based on clinical, X-ray, and multi-parametric MRI data, as well as combinations of these datasets. Each model was evaluated using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI). RESULTS: AUCs of 5 models using clinical, X-ray radiomics, MRI radiomics, X-ray plus MRI radiomics, and combination of all were 0.760 (95% CI: 0.583-0.937), 0.706 (95% CI: 0.506-0.905), 0.751 (95% CI: 0.572-0.930), 0.796 (95% CI: 0.629-0.963), 0.828 (95% CI: 0.676-0.980), respectively. The DeLong test showed no significant difference between any pair of models (p > 0.05). The combined model yielded higher performance than the clinical and radiomics models as demonstrated by net reclassification improvement (NRI) and integrated difference improvement (IDI) values, respectively. This combined model was also found to be clinically useful in the decision curve analysis (DCA). CONCLUSION: Modelling based on combination of clinical and radiomics data improves the ability to predict pathological responses to NAC in extremity high-grade osteosarcoma compared to the models based on either clinical or radiomics data.

Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE.

BACKGROUND: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. METHODS: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). RESULTS: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. CONCLUSIONS: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.

Circulating tumor DNA as a prognostic indicator of colorectal cancer recurrence-a systematic review and meta-analysis.

PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. After resection, patients need extensive follow-up to detect asymptomatic recurrences as early as possible to obtain optimal treatment. This study evaluated the prognostic value of circulating tumor DNA (ctDNA) for CRC recurrence. METHODS: Two investigators independently conducted a systematic literature search of peer-reviewed studies that investigated the prognostic value of ctDNA in CRC. Fixed effects or random effects models were applied for all analyses based on the assessment of heterogeneity. RESULTS: A total of 189 studies were initially retrieved from all databases; ultimately, eight studies with 879 CRC patients were included in this analysis. The pooled median recurrence-free survival was 11.36 months for ctDNA-positive patients. Meta-analysis of hazard ratio (HR) suggested that postoperative ctDNA-positive patients were more likely to experience cancer recurrence than ctDNA-negative patients (pooled HR: 5.41; 95% confidence interval (CI): 2.37-8.45). CONCLUSIONS: Successive monitoring of ctDNA status and follow-up with postoperative computed tomography (CT)/magnetic resonance imaging (MRI) are useful tools to detect early recurrence in postoperative ctDNA-positive patients.

A scoping review of the analytical literature concerning nonambulatory dairy cattle.

Nonambulatory dairy cattle pose a complex problem due to the challenges associated with prevention, appropriate treatment and management, and arriving at an accurate prognosis. There is a breadth of literature regarding this topic, of which there is currently no formal synthesis. The objective of this scoping review was to describe and characterize the literature investigating risk factors, sequela, preventions, treatments, and prognostic factors for nonambulatory conditions in dairy cattle, with the intent of qualitatively synthesizing knowledge of the topic and identifying gaps in the literature. A literature search was conducted in 6 databases and 2 conference proceeding archives, which returned 7,568 unique articles. Initial screening of abstracts resulted in 1,544 articles reviewed at the full-text stage, of which 379 were included for data extraction. Over 75% of the included literature was published after 1980, and the most common countries in which these studies took place were the United States (n = 72), Canada (18), Sweden (17), and Germany (17). Common eligibility criteria used for inclusion were geographic region (97) and parity (92). Of the 379 studies included in this review, 144 were randomized controlled trials and 235 were observational studies. The majority of the controlled trials assessed prevention of nonambulatory conditions (116), most commonly through supplementation of vitamin D (27) and calcium (25) or the provision of anionic salts (22). Of the 28 studies focusing on treatment of nonambulatory conditions, 26 focused on calcium administration. Becoming nonambulatory was evaluated as an outcome in 165 of the observational studies. Frequently measured risk factors for becoming nonambulatory included hematological variables, such as blood calcium (73), phosphorus (53) and magnesium (42), and other factors such as parity (35) and breed (22). Recovery from a nonambulatory condition was the outcome in 31 of the observational studies, with commonly measured prognostic indicators being calcium (9), phosphorus (9), and duration of recumbency (7). Nonambulatory disorders were measured as risk factors in 53 of the observational studies, with the most commonly assessed outcomes including disorders of the transition period (11), and death or euthanasia (11). The most common terms used to describe nonambulatory conditions were "milk fever" (199) and "parturient paresis" (147). These terms were only further defined with explicit symptomatic criteria in 193 of the 379 studies in this review. Recumbency was the most commonly used of these criteria (144), followed by inability to rise (55). Potential gaps in the literature concerning nonambulatory dairy cattle that were identified in the present review included investigation of prognostic indicators for recovery from nonambulatory conditions that are applicable on farm, treatment alternatives to calcium administration, and guidance regarding the appropriate usage of terms meant to categorize nonambulatory dairy cattle.

Electrophysiology as a prognostic indicator of visual recovery in diabetic patients undergoing cataract surgery.

PURPOSE: Visual outcomes after cataract surgery in diabetic patients with retinal or visual pathway disease are difficult to predict as the fundus may be obscured, and assessment of visual potential is challenging. This study assessed the value of visual electrophysiology as a prognostic indicator of visual recovery in diabetic patients with cataract, prior to cataract surgery. METHODS: Forty-one diabetic patients (aged 52-80; 74 eyes) and 13 age-matched non-diabetic control patients (21 eyes) were examined prior to cataract surgery. Pre-surgical examinations included best-corrected visual acuity (BCVA), slit-lamp bio-microscopy, ISCEV-standard full-field electroretinography (ffERG), and flash visual evoked potential (flash VEP) testing. Electrophysiological assessments included quantification of the DA and LA ERG, oscillatory potentials (OPs; OP1, OP2, OP3, OP4) and flash VEP P1, P2, and P3 components. Post-operative BCVA was measured in all cases and the diabetic patients grouped according to the severity of visual acuity loss: mild (logMAR ≤ 0.1), moderate (0.1 < logMAR < 0.5), or severe (logMAR ≥ 0.5). A fourth group included those without diabetes. The pre-surgical electrophysiological data was compared between the four groups by analysis of variance. RESULTS: The severity of post-surgical visual acuity loss in the diabetic patients was classified as mild (N=22 eyes), moderate (N=31 eyes), or severe (N=21 eyes). In the group without diabetes, post-surgical visual impairment was classified as mild (N=21 eyes). The pre-operative DA 10.0 ERG a-wave amplitudes, DA 3.0 ERG OP2 amplitudes, and the LA 3.0 a- and b-wave amplitudes showed best significant differences among the four groups. The flash VEP did not show significant difference between groups. CONCLUSION: Electrophysiological assessment of diabetic patients with cataract can provide a useful measure of retinal function. Full-field ERG components, including the DA 10.0 ERG a-wave, DA 3.0 ERG OP2 component, and the LA 3.0 a- and b-wave amplitudes, are of prognostic value in predicting post-surgical visual acuity, and may inform the surgical management of cataract patients with diabetes.

Prognostic Value of Blood-Based Inflammatory Biomarkers in Secondary Hemophagocytic Lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a rare systematic immune disease manifested with excessive activation of lymphocytes and macrophages. This study was designed to explore the feasible prognostic factors of secondary HLH (sHLH). METHOD: We retrospectively analyzed 179 patients with newly diagnosed sHLH from January 2016 to May 2019 according to the HLH-2004 protocol. Baseline characteristics and laboratory results were reviewed. RESULTS: The median age of all patients was 53 years, with a male/female ratio of 1.45. The commonest cause of HLH was malignancy. Of the 179 patients, 48.6% presented with Epstein-Barr virus (EBV) infection, 92.8% with hemocytopenia (at least 2 lineages), 60.3% with hypofibrinogenemia, 43.0% with hypertriglyceridemia (≥ 3 mmol/L), 99.4% with high ferritin, 97.8% with fever, 72.1% with splenomegaly, and 72.6% with hemophagocytosis. As to their prognosis, 122 patients died; the median survival was 88 days, with a 2-year survival rate of 26.72%. Univariate analysis confirmed neutrophil-to-lymphocyte ratio ˃ 2.53, lymphocyte-to-monocyte ratio (LMR) ≤ 4.43, platelet-to-lymphocyte ratio ˃ 227.27, red blood cell distribution width ˃ 14.6, red blood cell distribution width-to-platelet ratio (RPR) > 0.33, EBV infection, platelet ≤ 34 × 109 /L, fibrinogen ≤ 1.34 g/L, alkaline phosphatase ˃ 182.4 U/L, adenosine deaminase ˃ 69.2 U/L, and ferritin ˃ 2318 ng/mL were associated with an inferior survival. In a multivariate model, LMR, RPR, and ferritin were considered as three independent factors. CONCLUSION: Some blood-based inflammatory markers, which can be easily and cheaply detected, are significantly associated with the OS of HLH patients. LMR and RPR, superior to NLR, PLR, RDW, can be taken to predict the OS of patients with HLH.

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms.

BACKGROUND: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). METHODS: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. RESULTS: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. CONCLUSION: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.