Expression and clinical significance of PD-L1, B7-H3, B7-H4 and VISTA in craniopharyngioma

BackgroundCraniopharyngioma (CP) is a common refractory tumor of the central nervous system. However, little is known about the expression and clinical significance of B7 family ligands/receptors in CP patients. Thus, we conducted the present study to address this issue in a cohort of 132 CP cases.MethodsWe mapped and quantified the expression of B7 family ligands/receptors molecules programmed cell death ligand 1 (PD-L1), B7-H3, B7-H4 and V-domain Ig-containing suppressor of T cell activation (VISTA) in 89 adamantinomatous-type CP and 43 papillary-type CP samples using immunohistochemistry and immunofluorescence. Associations between the marker levels, clinicopathological variables and survival were evaluated.ResultsThe positive rates of PD-L1, B7-H3, B7-H4 and VISTA in the cohort of 132 CP cases were 76.5%, 100%, 40.2% and 80.3%, respectively. The cut-off values of PD-L1, B7-H3, B7-H4 and PD-L1 expression were determined by survival receiver operating characteristic (ROC) package, which was 70, 182, 0 and 20, respectively. Elevated expressions of PD-L1, B7-H3, B7-H4 and VISTA were significantly associated with some clinicopathological characteristics. Kaplan-Meier analysis indicated that higher VISTA expressions correlated with better overall survival (OS) and progression-free survival (PFS) (p=0.0053 and p=0.0066, respectively). Multivariate Cox regression analysis indicated that VISTA was an independent prognostic factor for OS (p=0.018) but not for PFS (p=0.898).ConclusionsWe found variable expression of PD-L1, B7-H3, B7-H4 and VISTA proteins in CPs. The results suggest that the expression level of VISTA may be used as an important indicator to predict the OS and PFS of CPs. B7 family ligands/receptors could be potential immunotherapeutic targets when treating CPs.

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Clinical Significance of SASH1 Expression in Glioma

Disease Markers ◽

10.1155/2015/383046 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Liu Yang ◽

Haitao Zhang ◽

Qi Yao ◽

Yingying Yan ◽

Ronghua Wu ◽

...

Keyword(s):

Clinical Significance ◽

Cox Regression ◽

Tissue Microarrays ◽

Suppressor Gene ◽

Clinicopathological Characteristics ◽

Postoperative Survival ◽

Low Grade ◽

Lower Grade ◽

Cox Regression Analysis ◽

Kaplan Meier

Objective.SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis.Methods.We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We usedFisher’s exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate.Results.SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival.Conclusions.SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma.

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Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study

Biomedicines ◽

10.3390/biomedicines9080971 ◽

2021 ◽

Vol 9 (8) ◽

pp. 971

Author(s):

Cecilia Marini ◽

Matteo Bauckneht ◽

Anna Borra ◽

Rita Lai ◽

Maria Isabella Donegani ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cox Regression ◽

Metabolic Response ◽

Progression Free Survival ◽

Disease Relapse ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Pet Ct ◽

Genome Sharing

Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS: According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97–60). RESULTS: Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan–Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION: Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.

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Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0177 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1265-1276 ◽

Cited By ~ 14

Author(s):

Nancy Ahmed ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Enken Drecoll ◽

Matthias Kotzsch ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Marker ◽

Residual Tumor ◽

Mrna Levels ◽

Serous Ovarian Cancer ◽

Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

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High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽

10.1186/s12885-020-07541-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Min Li ◽

Xue Cheng ◽

Rong Rong ◽

Yan Gao ◽

Xiuwu Tang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cox Regression ◽

Paraffin Section ◽

Progression Free Survival ◽

High Grade ◽

Serous Ovarian Cancer ◽

Systematic Analysis ◽

Cox Regression Analysis ◽

Genes Expression ◽

High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

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Predictors of tumor progression among children with gangliogliomas

Journal of Neurosurgery Pediatrics ◽

10.3171/2009.2.peds0861 ◽

2009 ◽

Vol 3 (6) ◽

pp. 461-466 ◽

Cited By ~ 25

Author(s):

Mostafa El Khashab ◽

Lynn Gargan ◽

Linda Margraf ◽

Korgun Koral ◽

Farideh Nejat ◽

...

Keyword(s):

Risk Factors ◽

Tumor Progression ◽

Cox Regression ◽

Tumor Resection ◽

Progression Free Survival ◽

Initial Presentation ◽

Subtotal Resection ◽

Low Grade ◽

Cox Regression Analysis ◽

Presenting Symptoms

Object Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. Methods A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. Results A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7 ± 4.2 years [± SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p = 0.004), tumor location in the cerebral hemisphere (p = 0.020), and complete tumor resection (p = 0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p = 0.028). Conclusions The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.

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The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽

10.1093/neuros/nyab052 ◽

2021 ◽

Author(s):

Peng Wang ◽

Chen Luo ◽

Peng-jie Hong ◽

Wen-ting Rui ◽

Shuai Wu

Keyword(s):

Cox Regression ◽

Progression Free Survival ◽

Extent Of Resection ◽

Lower Grade ◽

Wild Type ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Grade Glioma ◽

Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.444 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 444-444

Author(s):

Dimitrios Makrakis ◽

Daniel Castellano ◽

Ivan de Kouchkovsky ◽

Joseph J. Park ◽

Mehmet Asim Bilen ◽

...

Keyword(s):

Immune Checkpoint Inhibitor ◽

Overall Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Similar Proportion ◽

Multivariable Model ◽

Free Survival ◽

Cox Regression Analysis ◽

Response Table ◽

Advanced Urothelial Carcinoma

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]

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Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

10.21203/rs.3.rs-1070685/v1 ◽

2021 ◽

Author(s):

Xinxin Chen ◽

Wenxia Qiu ◽

Xuekun Xie ◽

Zefeng Chen ◽

Zhiwei Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Tumor Diameter ◽

Cox Regression Analysis ◽

Tumor Capsule ◽

Calibration Curves ◽

Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

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Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02633-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Renshen Xiang ◽

Wei Song ◽

Jun Ren ◽

Jing Wu ◽

Jincheng Fu ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cell ◽

Cell Activation ◽

Cox Regression ◽

Nk Cell ◽

Gene Set Enrichment Analysis ◽

Consensus Clustering ◽

Cox Regression Analysis ◽

Cell Enrichment ◽

Risk Scoring

Abstract Background Although numerous studies demonstrate the role of cancer stem cells in occurrence, recurrence, and distant metastases in gastric cancer (GC), little is known about the evolving genetic and epigenetic changes in the stem and progenitor cells. The purpose of this study was to identify the stem cell subtypes in GC and examine their clinical relevance. Methods Two publicly available datasets were used to identify GC stem cell subtypes, and consensus clustering was performed by unsupervised machine learning methods. The cancer stem cell (CSC) typing-related risk scoring (RS) model was established through multivariate Cox regression analysis. Results Cross-platform dataset-based two stable GC stem cell subtypes, namely low stem cell enrichment (SCE_L) and high stem cell enrichment (SCE_H), were prudently identified. Gene set enrichment analysis revealed that the classical oncogenic pathways, immune-related pathways, and regulation of stem cell division were active in SCE_H; ferroptosis, NK cell activation, and post-mutation repair pathways were active in SCE_L. GC stem cell subtypes could accurately predict clinical outcomes in patients, tumor microenvironment cell-infiltration characteristics, somatic mutation landscape, and potential responses to immunotherapy, targeted therapy, and chemotherapy. Additionally, a CSC typing-related RS model was established; it was strongly independent and could accurately predict the patient’s overall survival. Conclusions This study demonstrated the complex oncogenic mechanisms underlying GC. The findings provide a basis and reference for the diagnosis and treatment of GC.

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Prognostic and predictive value of FCER1G in glioma outcomes and response to immunotherapy

10.21203/rs.3.rs-98505/v2 ◽

2021 ◽

Author(s):

Houshi Xu ◽

Qingwei Zhu ◽

Lan Tang ◽

Junkun Jiang ◽

Huiwen Yuan ◽

...

Keyword(s):

T Cell Activation ◽

Predictive Value ◽

Cell Activation ◽

Immune Cell ◽

Cox Regression ◽

Glioma Patient ◽

Clinical Prognosis ◽

Multiple Factors ◽

Dismal Prognosis ◽

Geo Database

Abstract Purpose: Glioma is the most prevalent malignant form of brain tumors, with a dismal prognosis. Currently, cancer immunotherapy has emerged as a revolutionary treatment for patients with advanced highly aggressive therapy-resistant tumors. However, there is no effective biomarker to reflect the response to immunotherapy in glioma patient so far. So we aim to assess the clinical predictive value of FCER1G in patients with glioma. Methods: The expression level and correlation between clinical prognosis and FER1G levels were analyzed with the data from CGGA, TCGA, and GEO database. Univariate and multivariate cox regression model was built to predict the prognosis of glioma patients with multiple factors. Then the correlation between FCER1G with immune cell infiltration and activation was analyzed. At last, we predict the immunotherapeutic response in both high and low FCER1G expression subgroups.Results: FCER1G was significantly higher in glioma with greater malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio of FCER1G expression (Low versus High) was 0.66 and 95% CI is 0.54 to 0.79 (P <0.001), whereas age (HR=1.26, 95% CI=1.04-1.52), grade (HR=2.75, 95% CI=2.06-3.68), tumor recurrence (HR=2.17, 95% CI=1.81-2.62), IDH mutant (HR=2.46, 95% CI=1.97-3.01) and chemotherapeutic status (HR=1.4, 95% CI=1.20-1.80) are also included. Furthermore, we illustrated that gene FCER1G stratified glioma cases into high and low FCER1G expression subgroups that demonstrated with distinct clinical outcomes and T cell activation. At last, we demonstrated that high FCER1G levels presented great immunotherapeutic response in glioma patients.Conclusions: This study demonstrated FCER1G as a novel predictor for clinical diagnosis, prognosis, and response to immunotherapy in glioma patient. Assess expression of FCER1G is a promising method to discover patients that may benefit from immunotherapy.

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