Prognostic Predictive Value Research Articles

Preoperative CT for prediction of local recurrence after curettage of giant cell tumor of bone

•Preoperative CT images of GCTBs have value in prognostic prediction.•Certain features of GCTBs on CT images are related to local recurrence.•Our models' predictions for GCTB patients accepting extensive curettage are good.

The Prognostic Role and Nomogram Establishment of a Novel Prognostic Score Combining with Fibrinogen and Albumin Levels in Patients with WHO Grade II/III Gliomas.

PurposeWorld Health Organization (WHO) Grades II and III gliomas [also known as low grade gliomas (LGGs)] displayed different malignant behaviors and survival outcomes compared to Grade IV gliomas. This study aimed to identify the prognostic predictive value of a novel cumulative prognostic score [combined with fibrinogen and albumin levels (FA score)], establish and validate a point-based nomogram in LGG patients.Patients and MethodsA total of 91 patients who underwent total glioma resection at Shengjing Hospital of China Medical University between 2011 and 2013 were enrolled to establish a prognostic nomogram. All patients were histologically diagnosed as grades II/III, and never received radiotherapy or chemotherapy before surgery. Data collection included patient characteristics, clinicopathological factors, and preoperative hematology results. The performance of the nomogram was subsequently validated by the concordance index (c-index), calibration curve, and receiver operating characteristic (ROC) curve.ResultsThe FA score was negatively associated with the overall survival (OS) of LGG patients (p < 0.001). The results of multivariate analysis showed that FA score [p = 0.006, HR = 1.92, 95% confidence interval (CI): 1.21–3.05], age (p = 0.002, HR = 3.014, 95% CI:1.52–5.97), and white blood count (p < 0.001, HR = 4.24, 95% CI: 2.08–8.67) were independent prognostic factors for overall survival (OS). The study established a nomogram to predict OS with a c-index of 0.783 (95% CI, 0.72–0.84).ConclusionFA score might be a potential prognostic biomarker for LGG patients, and a reliable point-based nomogram will help clinicians to decide on the best treatment plans.

MYD88 Is a Potential Prognostic Gene and Immune Signature of Tumor Microenvironment for Gliomas.

PurposeTo explore the profiles of immune and stromal components of the tumor microenvironment (TME) and their related key genes in gliomas.MethodsWe applied bioinformatic techniques to identify the core gene that participated in the regulation of the TME of the gliomas. And immunohistochemistry staining was used to calculate the gene expressions in clinical cases.ResultsThe CIBERSORT and ESTIMATE were used to figure out the composition of TME in 698 glioma cases from The Cancer Genome Atlas (TCGA) database. Differential expression analysis identified 2103 genes between the high and the low-score group. Then the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, univariate Cox regression analysis, and protein–protein interaction (PPI) network construction were conducted based on these genes. MYD88 was identified as the key gene by the combination univariate Cox and PPI analysis. Furthermore, MYD88 expression was significantly associated with the overall survival and WHO grade of glioma patients. The genes in the high-expression MYD88 group were mainly in immune-related pathways in the Gene Set Enrichment Analysis (GSEA). We found that macrophage M2 accounted for the largest portion with an average of 27.6% in the glioma TIICs and was associated with high expression of MYD88. The results were verified in CGGA database and clinical cases in our hospital. Furthermore, we also found the MYD88 expression was higher in IDH1 wild types. The methylation rate was lower in high grade gliomas.ConclusionMYD88 had predictive prognostic value in glioma patients by influencing TIICs dysregulation especially the M2-type macrophages.

Novel predictive tools and therapeutic strategies for patients with initially diagnosed glottic cancer in the United States.

The objective of this study is to identify valuable prognostic factors, build clinical prediction nomograms, and recommend the optimal therapeutic strategy for patients with initially diagnosed glottic cancer. Patients were extracted from the SEER database. Cox regression analyses, survival analyses, an internal validation, the propensity score analysis, and the competing risk analysis were performed. Nine overlapped factors were considered as valuable prognostic factors. Furthermore, nomograms were established for clinical prediction models to assess the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that nomograms showed better predictive accuracy, ability, and prognostic value compared to the American Joint Committee on Cancer stage. For patients in stage I, primary site surgery alone would acquire best OS and CSS. For patients in stage II, primary site surgery and/or radiation would gain better OS and CSS. For patients in stage III, radiation plus chemotherapy or primary site surgery (alone or plus radiation) would acquire better OS and CSS. Moreover, for patients in stage IV, primary site surgery plus radiation would gain better OS and CSS. Nomograms could be useful for patients' counseling and guide therapeutic decision-making. Primary site surgery alone may likely be the optimal therapy for stage I glottic cancer, and primary site surgery and/or radiation may be the recommended therapy for stage II glottic cancer. The combination treatment would be the preferred choice for advanced-stage (stage III & IV) glottic cancer, and the role of chemotherapy needs to be further explored.

Seven interferon gamma response genes serve as a prognostic risk signature that correlates with immune infiltration in lung adenocarcinoma.

Interferon-gamma (IFN-γ) plays a complex role in modulating tumor microenvironment during lung adenocarcinoma (LUAD) development. In order to define the role of IFN-γ response genes in LUAD progression, we characterized the gene expression, mutation profile, protein-protein interaction of 24 IFN-γ response genes, which exhibited significant hazard ratio in overall survival. Two subgroups of LUAD from the TCGA cohort, which showed significant difference in the survival rate, were identified based on the expression of these genes. Furthermore, LASSO penalized cox regression model was used to derive a risk signature comprising seven IFN-γ response genes, including CD74, CSF2RB, PTPN6, MT2A, NMI, LATS2, and PFKP, which can serve as an independent prognostic predictor of LUAD. The risk signature was validated in an independent LUAD cohort. The high risk group is enriched with genes regulating cell cycle and DNA replication, as well as a high level of pro-tumor immune cells. In addition, the risk score is negatively correlated with the expression of immune metagenes, but positively correlated with DNA damage repair genes. Our findings reveal that seven-gene risk signature can be a valuable prognostic predictor for LUAD, and they are crucial participants in tumor microenvironment of LUAD.

Prognostic Factors and Predictive Value of MRD before Consolidation Therapy in Middle-risk Newly Diagnosed Young and Middle-aged Patients with AML

To explore the prognostic factors of young and middle-aged patients with acute myeloid leukemia (AML) and the predictive value of minimal residual disease (MRD) before consolidation therapy. The clinical data of 262 middle-risk young and middle-aged patients with AML treated in our hospital from January 2010 to December 2018 were selected retrospectively. All the patients were reached morphological leukemia-free state (MLFS) after induction chemotherapy, the overall and subgroup clinical data of the selected patients were analyzed. Cox regression model was used to evaluate the independent prognostic factors of middle-risk newly diagnosed young and middle-aged patients. Among the patients less than 40 years old treated by consolidation therapy with PR-CT and allo-HSCT regimens, the 5-year cumulative leukemia-free survival(LFS) rates were 40.92% and 63.51%（P=0.01）respectively, while those over 40 years old were 23.61% and 49.14%（P=0.00）, respectively. The 5-year cumulative LFS rates of the patients treated by chemotherapy and achieved early remission and late remission were 63.51% and 41.33% （P=0.01）, respectively. The 5-year cumulative overall survival(OS) rates of the patients treated by PR-CT and allo-HSCT regimens were 23.65% and 69.32% (P=0.00), respectively, and the 5-year cumulative LFS rates were 26.44% and 52.30% (P=0.01). Among the patients treated by PR-CT consolidation treatment, the MRD-negative and MRD-positive cases were 74 and 60 cases, respectively. The 5-year cumulative incidence of relapse rate in the MRD-negative subgroup was significantly lower than those in the MRD-positive subgroup (P<0.05), the 5-year LFS rate and OS rate of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). For the patients treated by allo-HSCT consolidation treatment, the MRD-negative and MRD-positive cases were 66 and 62 cases, respectively. The 5-year cumulative incidence of relapse rate of the patients in MRD-negative subgroup was significantly lower than those in MRD-positive subgroup（P<0.05）, and the 5-year LFS and OS rates of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). The univariate analysis results showed that age, chromosome karyotype, MRD status after reaching MLFS, and consolidation treatment regime were all related to the prognosis of patients (P<0.05). The multivariate analysis results showed that age, MRD status after reaching MLFS, and consolidation therapy were the independent factors affecting the cumulative OS rate of the patients (P<0.05). Chromosome karyotype was an independent factor affecting the cumulative LFS rate of the patients (P<0.05). MRD status and consolidation treatment plan after reaching MLFS were the independent factors affecting the cumulative recurrence rate of the patients (P<0.05). The OS rate of middle-risk young and middle-aged patients with newly diagnosed AML is independently related to age, MRD status after MLFS and consolidation therapy, while chromosome karyotype is independently related to cumulative LFS, and allo-HSCT consolidation therapy is recommended for middle-risk young and middle-aged AML patients after induction chemotherapy for MLFS, especially for those less than 40 years old and MRD positive before consolidation therapy.

Admission blood lactate levels of patients diagnosed with cerebrovascular disease effects on short- and long-term mortality risk.

Our study was carried out on patients admitted to the emergency ward with acute stroke symptoms that were subsequently diagnosed with cerebrovascular disease. We aimed to examine the relationship between these patients' admission lactate levels and their 1-, 3-, and 12-month mortality rates in order to evaluate the prognostic value of lactate levels. Our data were obtained retrospectively from 568 patients diagnosed with acute ischemic stroke at our emergency department between 1 January 2017 and 1 January 2018. Patient data were accessed via the hospital patient database. Included patients' files were assessed for examination and history taken at admission, comorbid diseases, demographic characteristics, treatments utilized, and laboratory results. Hyperlactatemia was defined as a lactate level of over 2mmol/L. The relationship between lactate levels and survival was investigated. Patients' complication rates after discharge were assessed alongside their 1-, 3-, and 12-month mortality. Our study assessed 568 patients. Out of these patients, 400 patients met our inclusion criteria and constituted the study population. These patients were separated into two groups according to their lactate levels. The hyperlactatemic group had a statistically significant increase in 1-, 3-, and 12-month mortality rates in comparison to the other group. Our study found that hyperlactatemia was associated with a higher risk of 1-, 3-, and 12-month mortality, suggesting that it has predictive prognostic value. In the future, we believe that prospective observational studies and/or large-scale retrospective studies will be of great value in providing more insight into this topic.

A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth.

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

Identifying Novel Cell Glycolysis-Related Gene Signature Predictive of Overall Survival in Gastric Cancer.

Background Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. The prognosis of GC remains poor due to its high malignancy, high incidence of metastasis and relapse, and lack of effective treatment. The constant progress in bioinformatics and molecular biology techniques has given rise to the discovery of biomarkers with clinical value to predict the GC patients' prognosis. However, the use of a single gene biomarker can hardly achieve the satisfactory specificity and sensitivity. Therefore, it is urgent to identify novel genetic markers to forecast the prognosis of patients with GC. Materials and Methods In our research, data mining was applied to perform expression profile analysis of mRNAs in the 443 GC patients from The Cancer Genome Atlas (TCGA) cohort. Genes associated with the overall survival (OS) of GC were identified using univariate analysis. The prognostic predictive value of the risk factors was determined using the Kaplan-Meier survival analysis and multivariate analysis. The risk scoring system was built in TCGA dataset and validated in an independent Gene Expression Omnibus (GEO) dataset comprising 300 GC patients. Based on the median of the risk score, GC patients were grouped into high-risk and low-risk groups. Results We identified four genes (GMPPA, GPC3, NUP50, and VCAN) that were significantly correlated with GC patients' OS. The high-risk group showed poor prognosis, indicating that the risk score was an effective predictor for the prognosis of GC patients. Conclusion The signature consisting of four glycolysis-related genes could be used to forecast the GC patients' prognosis.

Echocardiographic Abnormalities as Independent Prognostic Factors of In-Hospital Mortality among COVID-19 Patients

Introduction:Direct and indirect sequels of COVID-19 in the cardiovascular system are unclear. The present study aims to investigate the echocardiography findings in COVID-19 patients and possible correlations between the findings and the disease outcome.Methods:In this cross-sectional study, baseline characteristics and echocardiographic findings of hospitalized COVID-19 cases, and their correlation with mortality were evaluated. Furthermore, computed tomography (CT) angiography was performed to assess possible pulmonary embolism. In-hospital mortality was considered as the main outcome of the present study.Results:680 confirmed COVID-19 cases with the mean age of 55.15 ± 10.92 (range: 28 – 79) years were studied (63.09% male). Analysis showed that history of ischemic heart disease (RR=1.14; 95% CI: 1.08-1.19), history of hypertension (RR=1.04; 95% CI: 1.00-1.08), presence of embolism in main pulmonary artery (RR=1.53; 95% CI: 1.35-1.74), CT involvement more than 70% (RR=1.08; 95% CI: 1.1.01-1.16), left ventricular ejection fraction < 30 (RR=1.19; 95% CI: 1.07-1.32), pleural effusion (RR=1.08; 95% CI: 1.00-1.16), pulmonary artery systolic blood pressure 35 to 50 mmHg (RR=1.11; 95% CI: 1.03-1.18), right ventricular dysfunction (RR=1.54; 95% CI: 1.40-1.08), and collapsed inferior vena-cava (RR=1.05; 95% CI: 1.01-1.08) were independent prognostic factors of in-hospital mortality. Conclusion:Our study showed that cardiac involvement is a prevalent complication in COVID-19 patients. Echocardiography findings have independent prognostic value for prediction of in-hospital mortality. Since echocardiography is an easy and accessible method, echocardiography monitoring of COVID-19 patients can be used as a screening tool for identification of high-risk patients.

Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer

BackgroundThe growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients.MethodsWe explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers.ResultsCo-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317–3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ERα positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance.ConclusionData suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.

Succinylation Regulators Promote Clear Cell Renal Cell Carcinoma by Immune Regulation and RNA N6-Methyladenosine Methylation.

Succinylation is a newly discovered and multienzyme-regulated post-translational modification (PTM) that is associated with the initiation and progression of cancer. Currently, no systematic analyses on the role of succinylation regulators in tumors have been reported. In this study, we performed a comprehensive pan-cancer analysis on four well-known succinylation regulators (CPT1A, KAT2A, SIRT5, and SIRT7). We found that these regulators played specific and critical roles in the prognosis of clear cell renal cell carcinoma (ccRCC). We constructed a risk score (RS) based on two independent prognostic prediction factors, CPT1A and KAT2A, and subsequently developed a nomogram model containing the RS, which showed good accuracy in the prediction of overall survival (OS) in ccRCC patients. Furthermore, we used the similar expression pattern of four succinylation regulators according to consensus clustering analysis to divide the patients into three clusters that exhibited prominently different OS as well as clinicopathological characteristics. Differently expressed genes (DEGs) and pathway enrichment analyses of three clusters indicated that succinylation regulators might promote malignant progression of ccRCC by regulating the infiltration of immune cells and RNA N6-methyladenosine (m6A) methylation. Importantly, our data suggest that CPT1A and SIRT5 might up-regulate and down-regulate the expression of LRPPRC and EIF3B, respectively. Our study systematically analyzed the prognostic predictive values of four succinylation regulators and revealed their potential mechanisms in ccRCC aggressiveness. These data provide new insight into the understanding of succinylation modification and present clinical evidence for its role in ccRCC treatments.

Abstract PS4-45: Computerized image analysis of nuclear morphological features reveals differences in phenotype and prognosis of disease free survival of early stage ER+ breast cancers for South Asian and North American women

Abstract Background: Breast cancer is the most common cancer worldwide. There has been emerging interest in studying differences in breast tumor phenotypes between South Asian and South American women given that racial/ethnic disparities in incidence and mortality have been demonstrated in multiple studies. South Asian women are more likely to be diagnosed with an advanced stage breast tumor despite lower incidence than in North American women. There is evidence that computer-extracted nuclear morphological features on H&amp;E slide images may be associated with breast cancer aggressiveness, specifically recurrence and disease free survival. However, studies have mostly focused on North American women. In this work, we evaluated whether there is a difference in computer extracted features of nuclear morphology from H&amp;E tissue slide images between South Asian (SA) and North American (NA) women and we also investigated how these differences could impact the development of population specific breast cancer prognostic models. Methods: H&amp;E slides of breast tumors from patients who were diagnosed with ER+ early stage invasive breast cancer from Tata Memorial Centre, India (SA: 69 (20 recurrence)) and from University Hospitals Cleveland Medical Center (NA: 121 (20 recurrence)), along with outcome information were collected. All slides were digitized on either a Ventana DP 200 or a Roche Ventana iScan HT slide scanner. For each image, a conditional Generative Adversarial Network model was employed to segment the individual nuclei, which were used to generate 241 nuclear features including nuclear architecture, shape, orientation disorder, and texture features. Half of the patients (95) were randomly selected as the training set (Stra) with the remaining patients as the hold-out validation set (Stest). Three elastic net regularized Cox regression models (MSA, MNA, MSA+NA) were trained fitting between the nuclear features and disease free survival (DFS) respectively for SA subset, NA subset, and SA &amp; NA set in Stra. The top five prognostic features were identified respectively from each of the three models (MSA, MNA, MSA+NA) which were further validated on Stest to evaluate their prognostic value in prediction of DFS. Results: We found that the prognostic features identified by MNA and MSA+NA were mostly shape features (three out of five for MNA, four out of five for MSA+NA), while the prognostic features identified by the model specifically trained with the SA population (MSA) were mostly texture features (three out of five), possibly reflecting chromatin patterns in the cell. MSA yielded a better performance (Hazard Ratio=4.99 (p=0.00928, CI=1.32-18.9) from log-rank test between model derived high and low risk categories) on SA population in Stest compared to MNA and MSA+NA. Conclusion: We found that nuclear histomorphometry features were different between breast cancer patients from South Asia and those from North America. The prognostic capability of the computational pathology-based models for South Asian women could be significantly improved by taking into account population-specific information. An additional independent validation set is needed to confirm the preliminary findings presented here. Citation Format: Haojia Li, Kaustav Bera, Paula Toro, Pingfu Fu, Vidya Rao, Shabina Siddique, Aparna Harbhajanka, Haley Sechrist, Zelin Zhang, Sangeeta Desai, Vani Parmar, Anant Madabhushi. Computerized image analysis of nuclear morphological features reveals differences in phenotype and prognosis of disease free survival of early stage ER+ breast cancers for South Asian and North American women [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-45.

Abstract PS17-38: Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients

Abstract Background: The association between 21-gene recurrence score (RS) and host factors such as overweight remains unclear for breast cancer patients. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic predictive value of RS between overweight or non-overweight patients.Patients and methods: Luminal-like patients receiving surgery between January 2009 and December 2018 in the Comprehensive Breast Health Center, Shanghai Ruijin Hospital, with 21-gene RS results were retrospectively retrieved. Association and subgroup analysis between BMI and 21-gene RS were conducted. Single-gene expression in 21-gene RS panel was compared between overweight and non-overweight groups. Recurrence-free survival (RFS) and overall survival (OS) were calculated according to RS category and BMI status.Results: Among 1876 patients included, 442 (23.56%), 995 (53.04%) and 439 (23.40%) were classified into low, intermediate and high risk groups. RS category was significantly differently distributed between overweight and non-overweight patients (P=0.035). Overweight patients had a trend of lower RS score than patients with normal weight (25.13 vs 26.17, P=0.080). The effect of BMI on RS significantly varied according to age (P=0.012) and menstruation status (P&amp;lt;0.001). Compared to non-overweight patients, overweight ones presented with higher ER (P&amp;lt;0.001), PR (P&amp;lt;0.001), CEGP1 (P=0.017), Ki67 (P=0.020) and STMY3 (P=0.026) mRNA expression levels. Regarding menstrual status, postmenopausal women with BMI≥24 kg/m2 were associated with higher ER group score (P&amp;lt;0.001), with higher ER (P=0.041), PR (P&amp;lt;0.001), CEGP1 (P=0.005), as well as GRB7 (P=0.015) expression, which was not significant in premenopausal women. After a median follow-up of 39.40 months (range 1.67-119.53), overweight patients had similar RFS (P=0.670) and OS (P=0.077) to non-overweight ones. Moreover, RS category could significantly predict RFS in the whole population (P&amp;lt;0.001), in either those overweight (P=0.003) or non-overweight (P=0.019).Conclusion: 21-gene RS was differently distributed between overweight and non-overweight patients, which interacted with age and menopausal status. ER, PR, CEGP1, Ki67 and STMY3 genes were more expressed in overweight patients. RS category could predict RFS regardless of BMI status, which warranted further validation. Citation Format: Yiwei Tong, Weiqi Gao, Jiayi Wu, Siji Zhu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Xiaosong Chen. Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-38.

Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer.

The 21-gene Recurrence Score (RS) assay has been validated as both a prognostic and predictive tool in node-negative (pN0), estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer. A large body of evidence supports the clinical utility of the RS in the node positive (pN+) population as well. Retrospective analyses of archived tissue from multiple clinical trials have found the RS to be prognostic in both endocrine therapy (ET)-treated and chemotherapy-treated patient with pN+ disease. Distribution of RS results in pN+ patients have also been consistent with those of pN0 populations. Data from the SWOG 8814 trial and large population-based registries further support the prognostic and potential predictive value of the RS. Specifically, patients with 1 to 3 positive nodes and RS less than 18 derived negligible benefit from adjuvant chemotherapy in these studies. In the prospective West German Study Group PlanB and ADAPT trials, pN+ patients with RS less than 11 and RS 25 or less, respectively, who were treated with ET alone experienced excellent outcomes. Finally, 5-year results of the RxPONDER clinical trial randomizing patients with 1 to 3 positive nodes and RS 25 or less to ET alone vs ET plus chemotherapy confirmed an absence of chemotherapy benefit in postmenopausal patients. Clinical practice guidelines support use of the RS in the pN+, ER+/HER2- population, and many institutions have adopted the RS to guide clinical decisionmaking, resulting in a net reduction of adjuvant chemotherapy use. This review highlights the existing data supporting the prognostic and predictive ability of the RS in pN+ disease, current practice patterns related to RS use in this population, and emerging applications.

Kinetics and prognostic value of soluble VCAM-1 in ST-segment elevation myocardial infarction patients.

BackgroundSoluble vascular cell adhesion molecule‐1 (sVCAM‐1) is a biomarker of endothelial activation and inflammation. There is still controversy as to whether it can predict clinical outcome after ST‐elevation myocardial infarction (STEMI). Our aim was to assess the sVCAM‐1 kinetics and to evaluate its prognostic predictive value.MethodWe prospectively enrolled 251 consecutive STEMI patients who underwent coronary revascularization in our university hospital. Blood samples were collected at admission, 4, 24, 48 h and 1 month after admission. sVCAM‐1 serum level was assessed using ELISA assay. All patients had cardiac magnetic resonance imaging at 1‐month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were recorded over 12 months after STEMI.ResultssVCAM‐1 levels significantly increased from admission up to 1 month and were significantly correlated with IS, LVEF, and LV end‐systolic and diastolic volume. (H48 area under curve (AUC) ≥ H48 median) were associated with an increased risk of adverse clinical events during the 12‐month follow‐up period with a hazard ratio (HR) = 2.6 (95% confidence interval [CI] of ratio = 1.2–5.6, p = .02). The ability of H48 AUC for sVCAM‐1 to discriminate between patients with or without the composite endpoint was evaluated using receiver operating characteristics with an AUC at 0.67 (0.57–0.78, p = .004). This ability was significantly superior to H48 AUC creatine kinase (p = .03).ConclusionsIn STEMI patients, high sVCAM‐1 levels are associated with a poor clinical outcome. sVCAM‐1 is an early postmyocardial infarction biomarker and might be an interesting target for the development of future therapeutic strategies.

Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients.MethodsWhole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan–Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients.ResultsThe mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan–Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA.ConclusionsMutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.

Association of Urinary Matrix Metalloproteinase 7 Levels With Incident Renal Flare in Lupus Nephritis.

Flares of lupus nephritis (LN) are frequent and associated with impaired renal prognosis. One major management obstacle in LN flare is the lack of effective methods to identify at-risk patients earlier in their disease course. This study was undertaken to test the utility of measurement of urinary matrix metalloproteinase 7 (MMP-7) for the dynamic surveillance of renal disease activity and prediction of renal flares in LN. A prospective, 2-stage cohort study was performed in patients with LN. Urinary MMP-7 levels at the time of biopsy were evaluated in 154 patients with newly diagnosed LN in 2 independent cohorts. Urinary MMP-7 levels were assessed for correlation with renal histologic activity. Furthermore, after a minimum period of 12 months of renal disease remission, urinary MMP-7 levels were monitored bimonthly for 2 years in 65 patients with LN. The association between urinary MMP-7 levels and development of LN flare was analyzed. Urinary MMP-7 levels were elevated in patients with LN. A higher urinary MMP-7 level in LN was associated with greater renal histologic activity. As a marker for identifying LN patients with more severe renal histologic activity (i.e., a histologic activity index of ≥7), the level of urinary MMP-7 outperformed other clinical markers and improved their predictive performance, thus linking urinary MMP-7 levels to renal disease activity. Furthermore, among patients who had follow-up measurements of urinary MMP-7 after achievement of long-term remission of renal disease activity, an elevated urinary MMP-7 level during follow-up was independently associated with an increased risk of LN flare. This elevation in the urinary MMP-7 level hinted at the risk of an LN flare at an earlier time point prior to indications using conventional laboratory measures. Thus, use of the urinary MMP-7 level in conjunction with other clinical measures improved the prognostic value for prediction of an LN flare. Urinary MMP-7 levels in LN are correlated with renal histologic activity. An elevated urinary MMP-7 level detected after achievement of long-term renal disease remission is associated with a higher risk of incident renal flare in patients with LN.

The Landscape and Prognostic Value of m6A Methylation-related Genes in Low Grade Glioma

Background: Low-grade glioma (LGG) can behave aggressively, akin to glioblastoma, and prognostic classification is urgently needed. N6-methyladenosine (m6A) modification is a key regulator of transcriptional expression during tumorigenesis and progression. This study aimed to identify transcriptome biomarkers with prognostic predictive value and define molecular subclassifications. Methods: We selected 21 m6A methylation-related genes for analysis of 529 LGG samples from TCGA LGG datasets and 1,152 brain tissues from the GTEx datasets. Through difference analysis, Protein-protein interactions (PPI) network, and spearman correlation analysis, gene expression and correlation were studied. Consensus cluster, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes, and Genomes (KEGG) analysis were performed for classification and functional analysis. Lasso Cox regression algorithm and univariate and multivariate analyses were used for assessing risk factors. Results: The expression of m6A methylation-related genes between normal brain and LGG samples was significantly different. Consensus cluster analysis clearly divided LGG samples into two categories, with a p-value for the difference between prognosis close to 0. Through the lasso Cox regression algorithm and univariate and multivariate analyses, four genetic biomarkers (IGF2BP2, IGF2BP3, YTHDC1, and ALKBH3) were screened out, and the cumulative analysis of these effectively predicted patients’ prognosis. Conclusion: Consensus cluster analysis based on m6A methylation-related genes clearly divided LGG samples into two categories. Moreover, the cumulative analysis of four genetic biomarkers (IGF2BP2, IGF2BP3, YTHDC1, and ALKBH3) effectively predicted prognosis.

Can we estimate cytokine storm from initial computed tomography images of Coronavirus disease-2019 patients?

The present study aims to investigate whether elementary lesions detected at the time of the diagnosis, their distribution characteristics, and CT scoring can be predictive of a cytokine storm. CT might have a prognostic predictive value beyond its diagnostic value. Sixty-eight patients, 32 with cytokine storm and 36 without cytokine storm, were included in the study. Four different scoring methods were created according to elementary lesions, distribution and involvement rate. CT scores and demographic findings of the cases were compared in the cytokine storm and non-cytokine storm groups. The mean age of patients was 57.72 (SD: 13.5) and 40 (58.8 %) of them were male. The cytokine storm was significantly more common among male patients and patients of older age (p=0.04). The AUC values of CT score 1, CT score 2, CT score 3, and CT score 4 were as follows; 0.772 (95% CI; 0.651-0.892), 0.766 (95% CI; 0.647-0.885), 0.758 (95% CI; 0.639-8.78), and 0.760 (95% CI; 0.640-0.881), respectively. All CT scores had better predictive values in males. CT scoring at the time of admission can be used to predict cases that may develop cytokine storm later (Tab. 4, Fig. 2, Ref. 15).