scholarly journals Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1268 ◽  
Author(s):  
Yuqian Gao ◽  
Yi-Ting Wang ◽  
Yongmei Chen ◽  
Hui Wang ◽  
Denise Young ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Survival Rates ◽  
Standard Of Care ◽  
Driver Genes ◽  
Primary Tumors ◽  
Entire Cohort ◽  
Risk Patients ◽  
Prostate Cancers

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.

scholarly journals Extracellular miRNAs as Biomarkers of Head and Neck Cancer Progression and Metastasis

2019 ◽  
Vol 20 (19) ◽  
pp. 4799 ◽  
Author(s):  
Zuzanna Nowicka ◽  
Konrad Stawiski ◽  
Bartłomiej Tomasik ◽  
Wojciech Fendler
Keyword(s):  
Head And Neck ◽  
Cancer Progression ◽  
Treatment Options ◽  
Survival Rates ◽  
Chemotherapy Resistance ◽  
Second Primary ◽  
Special Focus ◽  
Primary Tumors ◽  
Extracellular Mirnas ◽  
Extracellular Mirna

Head and neck squamous cell carcinomas (HNSCCs) contribute to over 300,000 deaths every year worldwide. Although the survival rates have improved in some groups of patients, mostly due to new treatment options and the increasing percentage of human papillomavirus (HPV)-related cancers, local recurrences and second primary tumors remain a great challenge for the clinicians. Presently, there is no biomarker for patient surveillance that could help identify patients with HNSCC that are more likely to experience a relapse or early progression, potentially requiring closer follow-up or salvage treatment. MicoRNAs (miRNAs) are non-coding RNA molecules that posttranscriptionally modulate gene expression. They are highly stable and their level can be measured in biofluids including serum, plasma, and saliva, enabling quick results and allowing for repeated analysis during and after the completion of therapy. This has cemented the role of miRNAs as biomarkers with a huge potential in oncology. Since altered miRNA expression was described in HNSCC and many miRNAs play a role in radio- and chemotherapy resistance, cancer progression, and metastasis, they can be utilized as biomarkers of these phenomena. This review outlines recent discoveries in the field of extracellular miRNA-based biomarkers of HNSCC progression and metastasis, with a special focus on HPV-related cancers and radioresistance.

Patient-Doctor Contact Interval and Clinical Outcomes in Continuous Ambulatory Peritoneal Dialysis Patients

2017 ◽  
Vol 45 (4) ◽  
pp. 346-352 ◽  
Author(s):  
Chunyan Yi ◽  
Qunying Guo ◽  
Jianxiong Lin ◽  
Jianying Li ◽  
Xueqing Yu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Outcomes ◽  
Operating Characteristic ◽  
Patient Survival ◽  
Characteristic Curve ◽  
Survival Rates ◽  
Guangzhou City ◽  
Clinical Events ◽  
The Mean

Background: The optimal patient-doctor contact (PDC) interval remains unknown in peritoneal dialysis (PD) patients. The aim was to investigate the association between PDC interval and clinical outcomes in continuous ambulatory PD (CAPD) patients. Methods: In this retrospective cohort study, CAPD patients who resided in Guangzhou city between January 2006 and December 2012 were included. According to receiver operating characteristic curve analysis, all patients were classified as high (PDC interval ≤2 months) and low (PDC interval >2 months) PDC frequency groups. Biochemical data, clinical events, and clinical outcomes during the follow-up period were compared. Results: Of 433 CAPD patients, the mean age was 51.3 ± 15.7 years, 54.3% of patients were male, and 29.1% with diabetes. The median vintage of PD was 45.8 (26.3-69.1) months. Patients with high PDC frequency (n = 233) had better patient-survival rates (99.6, 87.7, and 76.5% vs. 92.7, 76.5, and 58.7% at 1, 3, and 5 years; p < 0.001), lower peritonitis rate (0.17 vs. 0.23 episodes per patient-year; p < 0.001), and hospitalization rate (0.49 vs. 0.67 episodes per patient-year; p < 0.001) than those in the low PDC frequency group (n = 200). After adjustment for confounders, PDC interval of no more than 2 months was independently associated with better patient survival (hazard ratio 0.60, 95% CI 0.42-0.86, p = 0.006). Conclusion: A PDC interval of 2 months or less was associated with better clinical outcomes in CAPD patients. This indicates that a shorter PDC interval should be encouraged for them to achieve better clinical outcomes.

scholarly journals Benefit of [18F]-FDG PET/CT for treatment-naïve nasopharyngeal carcinoma

2021 ◽  
Author(s):  
Shan-Shan Yang ◽  
Yi-Shan Wu ◽  
Wei-Chao Chen ◽  
Jun Zhang ◽  
Su-Ming Xiao ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Risk Stratification ◽  
Lymph Nodes ◽  
Characteristic Curve ◽  
Survival Rates ◽  
High Risk Patients ◽  
Pet Ct ◽  
Risk Patients ◽  
Score Model

Abstract Background To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. Methods The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. Results PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). Conclusion PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

Retinal vascular speed <0.5 disc diameter per week as an early sign of retinopathy of prematurity requiring treatment

2018 ◽  
Vol 28 (4) ◽  
pp. 441-445 ◽  
Author(s):  
Ana M Solans Pérez de Larraya ◽  
José M Ortega Molina ◽  
José Uberos Fernández ◽  
Júlia Escudero Gómez ◽  
Andrés D Salgado Miranda ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Retinopathy Of Prematurity ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Standard Of Care ◽  
University Hospital ◽  
Disc Diameter ◽  
Unit Of Length ◽  
Stage 1 ◽  
Careful Documentation

Purpose: To analyse the speed of temporal retinal vascularisation in preterm infants included in the screening programme for retinopathy of prematurity. Material and methods: A total of 185 premature infants were studied retrospectively between 2000 and 2017 in San Cecilio University Hospital of Granada, Spain. The method of binocular indirect ophthalmoscopy with indentation was used for the examination. The horizontal disc diameter was used as a unit of length. Speed of temporal retinal vascularisation (disc diameter/week) was calculated as the ratio between the extent of temporal retinal vascularisation (disc diameter) and the time in weeks. Results: The weekly temporal retinal vascularisation (0–1.25 disc diameter/week, confidence interval) was significantly higher in no retinopathy of prematurity (0.73 ± 0.22 disc diameter/week) than in stage 1 retinopathy of prematurity (0.58 ± 0.22 disc diameter/week). It was also higher in stage 1 than in stages 2 (0.46 ± 0.14 disc diameter/week) and 3 of retinopathy of prematurity (0.36 ± 0.18 disc diameter/week). The rate of temporal retinal vascularisation (disc diameter/week) decreases when retinopathy of prematurity stage increases. The area under the receiver operating characteristic curve was 0.85 (95% confidence interval: 0.79–0.91) for retinopathy of prematurity requiring treatment versus not requiring treatment. The best discriminative cut-off point was a speed of retinal vascularisation <0.5 disc diameter/week, with a sensitivity and a specificity of 84.8% and 77%, respectively. Conclusion: The rate of temporal retinal vascularisation is a quantifiable observation that can help to alert a clinician that treatment of retinopathy of prematurity may be required. However, before becoming a new standard of care for treatment, it requires careful documentation, with agreement between several ophthalmologists.

Completion time in prostate cancer treated with proton beam therapy: Do interruptions matter?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Shaakir Hasan ◽  
Lane Rosen ◽  
Henry Tsai ◽  
Christopher Sinesi ◽  
George E Laramore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Completion Time ◽  
Characteristic Curve ◽  
Proton Beam Therapy ◽  
Collaborative Group ◽  
Kaplan Meier ◽  
Treatment Interruptions ◽  
Risk Patients ◽  
Prostate Cancers

e17553 Background: The association between completion time of proton therapy(PT) in prostate cancer and biochemical control is unknown. Methods: We queried the multi-institutional, prospectively collected, proton collaborative group registry for prostate cases treated definitively with PT. Kaplan meier methodology was used for biochemical failure free (bFF) rates and multivariable regression analyses (MVA) were used to identify correlates of treatment interruptions (TI) and bF. Results: After exclusion, 2794 men with 693 low, 869 favorable intermediate, 627 unfavorable intermediate, and 605 high risk prostate cancers had available data. The median age was 68 years(40-92), 90% were white and 8% were black. Androgen deprivation therapy (ADT) was given to 676 patients, 312 treatments were hypofractionated, and median EQD2 dose = 75(74-86) GyE1.5. Kaplan-meier median follow-up was 79 months. In total 900 patients (32%) had at least one TI. Shorter treatments (HR = 0.95 per day, P < 0.01) and high risk (HR = 0.72, P < 0.04) cases were less likely to have Tis on MVA. There was no difference in 5-year bFF rate with (92.7) and without (93.1%) TIs. In a subset of only high risk patients treated with ADT (n = 385), the 5-year bFF was 83% without TIs and 75% with TIs (HR = 2.10, P = 0.06). This discrepancy was significant with multivariable binomial regression (HR = 2.36, P = 0.03), and the bF difference was greatest when > 5 treatment days were missed per receiver operating characteristic curve. Conclusions: Largely, there was no correlation between TIs and bF in prostate cancer treated with PT, however completion time may play a more significant role in high risk disease.

scholarly journals Prediction and Analysis of Skin Cancer Progression using Genomics Profiles of Patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sherry Bhalla ◽  
Harpreet Kaur ◽  
Anjali Dhall ◽  
Gajendra P. S. Raghava
Keyword(s):  
Cancer Progression ◽  
Cutaneous Melanoma ◽  
Prediction Models ◽  
Survival Rates ◽  
Validation Dataset ◽  
Support Vector ◽  
Melanoma Metastasis ◽  
Primary Tumors ◽  
Genomic Features ◽  
Optimal Therapeutic Strategy

Abstract The metastatic Skin Cutaneous Melanoma (SKCM) has been associated with diminished survival rates and high mortality rates worldwide. Thus, segregating metastatic melanoma from the primary tumors is crucial to employ an optimal therapeutic strategy for the prolonged survival of patients. The SKCM mRNA, miRNA and methylation data of TCGA is comprehensively analysed to recognize key genomic features that can segregate metastatic and primary tumors. Further, machine learning models have been developed using selected features to distinguish the same. The Support Vector Classification with Weight (SVC-W) model developed using the expression of 17 mRNAs achieved Area under the Receiver Operating Characteristic (AUROC) curve of 0.95 and an accuracy of 89.47% on an independent validation dataset. This study reveals the genes C7, MMP3, KRT14, LOC642587, CASP7, S100A7 and miRNAs hsa-mir-205 and hsa-mir-203b as the key genomic features that may substantially contribute to the oncogenesis of melanoma. Our study also proposes genes ESM1, NFATC3, C7orf4, CDK14, ZNF827, and ZSWIM7 as novel putative markers for cutaneous melanoma metastasis. The major prediction models and analysis modules to predict metastatic and primary tumor samples of SKCM are available from a webserver, CancerSPP (http://webs.iiitd.edu.in/raghava/cancerspp/).

scholarly journals Early and multiple origins of metastatic lineages within primary tumors

2016 ◽  
Vol 113 (8) ◽  
pp. 2140-2145 ◽  
Author(s):  
Zi-Ming Zhao ◽  
Bixiao Zhao ◽  
Yalai Bai ◽  
Atila Iamarino ◽  
Stephen G. Gaffney ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Evolutionary Process ◽  
Driver Mutations ◽  
Cancer Evolution ◽  
Driver Genes ◽  
Genetic Changes ◽  
Primary Tumors ◽  
Multiple Origins

Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.

scholarly journals NAA10 as a New Prognostic Marker for Cancer Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8010
Author(s):  
Sun Myung Kim ◽  
Eunyoung Ha ◽  
Jinyoung Kim ◽  
Chiheum Cho ◽  
So-Jin Shin ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Survival Rates ◽  
Cancer Prognosis ◽  
Biological Functions ◽  
Invasion And Metastasis ◽  
Lysine Residues ◽  
Terminal Amino ◽  
Prostate Cancers

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.

669 Mortality Risk Prediction for Emergency Laparotomy: Are We Utilising the Best Tool?

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
M Barghash ◽  
A Iskandar ◽  
S Fawzy ◽  
T Elghobashy ◽  
F Salimi ◽  
...  
Keyword(s):  
Predictive Power ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Scoring Systems ◽  
Emergency Laparotomy ◽  
Discriminative Power ◽  
Entire Cohort ◽  
Possum Score ◽  
The Common ◽  
The Uk

Abstract Aim Emergency laparotomy is one of the common operations performed in the UK. To aid in more objective decision making, several scoring systems have been formulated. In this project, we aimed to explore the predictive power of both NELA and P-Possum mortality scores against 30 days and 90 days observed mortality for emergency laparotomy patients. Method Patient details from two large district general hospitals were extracted from the NELA database over a period of three years. Pre-operative NELA, post-operative NELA, and P-POSSUM predicted mortality were calculated and compared with the observed 30 days and 90 days mortality for the entire cohort. Model discrimination (statistical accuracy) was tested by calculating the area under the receiver operating characteristic curve (AUC), which was used to assess how accurately the model could discriminate. Results There were 378 patients eligible for inclusion with a median age of 64. 39 patients (10.3%) died within 30 days and 52 patients (13.8%) died within 90 days. P-POSSUM score, pre-operative NELA, and post-operative NELA scores predicted the 30 days mortality as (2.7%, 3.7%, and 2.4%) and 90 days mortality as (2.9%, 4.8%, and 4%) respectively. The discriminative power for 30 days and 90 days mortality was highest for the pre-operative NELA score (AUC 0.870, CI: 0.824 – 0.916), (AUC 0.826, CI: 0.769 – 0.884) respectively. Conclusions Both NELA and P-Possum scores underpredicted actual 30 days and 90 days mortality. It was however noted that the pre-operative NELA mortality score showed more accurate mortality discriminative power than the other 2 tested tools.

scholarly journals P297 Novel serum soluble markers of histological healing in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S302-S302
Author(s):  
O M Nardone ◽  
L Jeffery ◽  
A Bazarova ◽  
A Acharjee ◽  
G Gkoutos ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Operating Characteristic ◽  
Demographic Data ◽  
Characteristic Curve ◽  
Standard Of Care ◽  
Inflammatory Proteins ◽  
Histological Remission ◽  
Cell Adhesion Molecule 1 ◽  
Enhancement Technologies

Abstract Background The recent introduction of a commercial panel of soluble biomarkers, that can predict endoscopic healing, may support the monitoring and management of Crohn’s disease reducing the need of repeated endoscopy.1 Achieving histological remission (HR) is currently considered to be an important target in ulcerative colitis (UC).2 The aim of this study was to identify serological markers of HR in patients with UC and determine their diagnostic accuracy individually and in combination to predict HR. Methods We enrolled 40 UC patients referred to a tertiary academic centre for colonoscopy as part of standard of care. Demographic data and histologic data (RHI, Nancy) were collected. Concentrations of these biomarkers were compared with the histology at the time that the patients underwent colonoscopy with advanced enhancement technologies and targeted biopsies. Histological healing was defined as Nancy ≤1 and RHI ≤3. A total of 55 soluble analytes, relevant to inflammation or shown to be altered in IBD, were measured in serum using Procartaplex luminex assays (ThermoFisher). Finally, 24 analytes that were detected in more than 40% of patients were selected in downstream modelling and used to train a logistic regression model. Results We identified Brain-Derived Neurotrophic Factor (BDNF) and Macrophage Inflammatory Proteins (MIP-1 α) that, when combined together, showed the highest predictive power for predicting RHI≤3 and Nancy ≤ 1 with an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% CI: 0.69–0.97). When we investigated analytes separately for predicting the same outcome, univariate logistic regression was significant for two other markers: Leukemia Inhibitory Factor (LIF) and Vascular Cell Adhesion Molecule 1 (sVCAM1) showing higher values associated with the lack of healing. The AUROC was 0.74 for LIF (95% CI: 0.591–0.89) and 0.72 for sVCAM1 (95% CI: 0.53–0.90). Conclusion BDNF, MIP-1α, LIF and sVCAM may be promising markers to assess histological healing in UC patients. Replication in larger cohorts of patients is now required. *OMN and LJ contributed equally. References

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