Development of a novel liquid biopsy test to diagnose and locate gastrointestinal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1557-1557
Author(s):  
Yuying Wang ◽  
Jianchao Zheng ◽  
Zhilong Li ◽  
Ruijingfang Jiang ◽  
Jiaxi Peng ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Cross Validation ◽  
Validation Cohort ◽  
Classification Model ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Training Cohort ◽  
Cancer Types ◽  
Gi Cancers ◽  
Tissue Of Origin

1557 Background: Cancers of the gastrointestinal (GI) system, including esophagus, stomach, pancreas, gallbladder, liver, bile duct, colon, and rectum are estimated to account for 38% of all cancer incidences and nearly 46% of cancer-related deaths in China. We conducted a multi-center study to evaluate the feasibility of using genetic and epigenetic abnormalities in plasma cfDNA to diagnose and locate GI cancers. Methods: We performed parallel genetic and epigenetic profiling of plasma cfDNA from hepatocellular carcinoma (HCC), colorectal cancer (CRC) and pancreatic cancer (PC) patients as well as age-matched healthy individuals by ultra-deep sequencing targeting cancer driver genes, and by targeted bisulfite sequencing covering genome-wide CpG islands, shelves, and shores. Results: Using a pre-specified mutation scoring system, we found that cfDNA mutation profiling achieved a sensitivity of 59.6%, 67.2%, and 46.8% for detecting HCC (n = 322), CRC (n = 244) and PC (n = 141) respectively, with a specificity of 95% in healthy controls (n = 207). For 901 plasma cfDNA samples that underwent methylome profiling, we first applied a machine learning approach to classify each cancer type versus healthy controls in the training cohort (HCC: n = 125; CRC: n = 105; PC: n = 97; healthy individuals: n = 84). Random Forest models with 10-fold cross validation achieved an AUC of 0.96±0.04,0.89±0.06, 0.91±0.07 for HCC, CRC, and PC, respectively. Further analyses were performed on the validation cohort, including 172 HCC patients, 162 CRC patients, 60 PC patients, and an independent cohort of healthy individuals (HCC validation: n = 63; HCC independent validation: n = 109; CRC validation: n = 104; CRC external validation: n = 58; PC validation: n = 60; healthy controls: n = 96). The trained model achieved a sensitivity of 83.1% (specificity = 95.8%), 89.5% (specificity = 95.8%), and 76.7% (specificity = 91.7%) for HCC, CRC, and PC, respectively. Using regional methylation markers from diagnostic models for individual cancer types, we built a tissue-of-origin classification model, which achieved a cross-validation accuracy of 83.3% in the training cohort and an accuracy of 80.1% in the validation cohort in assigning correct cancer types. Conclusions: Plasma cfDNA methylome profiling identified effective biomarkers for the detection and tissue-of-origin determination of GI cancers, and outperformed mutation-based detection approach. Therefore, a liquid biopsy test capable of detecting and locating GI cancers is feasible and may serve as a valuable tool for early detection and intervention.

scholarly journals AB1242 A NOVEL BIOMARKER OF MMP-CLEAVED PROLARGIN IS ELEVATED IN PATIENTS WITH PSORIATIC ARTHRITIS COMPARED TO OTHER FIBRO-INFLAMMATORY DISEASES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1912-1913
Author(s):  
D. Sinkeviciute ◽  
A. Schlemmer ◽  
E. Berg Schmidt ◽  
A. C. Bay-Jensen ◽  
M. Karsdal ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Validation Cohort ◽  
Full Time ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Discovery Cohort ◽  
Low Disease Activity ◽  
Technical Validation ◽  
Full Time Employee

Background:Psoriatic Arthritis (PsA) is a chronic inflammatory disease, characterized by involvement of skin, axial and peripheral skeleton. Prolargin is a class II small leucine-rich proteoglycan found to be expressed in connective tissues of patients with PsA, and previously suggested to be remodelled upon treatment. Fragments of prolargin could quantify tissue turnover in individuals with PsA and reflect pathological tissue changes in these patients.Objectives:This study aimed at developing an immunoassay targeting a neo-epitope of prolargin cleaved by matrix metalloproteinases (MMPs), named PROM; and measure PROM levels in serum from two cohorts of patients affected by PsA and healthy controls.Methods:Development of a novel immunoassay targeting a specific MMP-generated neo-epitope fragment of prolargin (PROM) together with technical validation was performed, and then evaluated in serum from two independent cohorts. The technical validation included inter- and intra-variation, linearity, spiking recovery, stability and specificity. Specificity was tested using an elongated peptide, a truncated peptide and a non-sense peptide. The Discovery Cohort consists of 13 healthy individuals and 11 PsA patients, mean age 58, 60.3% female and 100% caucasian. The Validation Cohort included 35 healthy individuals and 112 PsA patients with low disease activity included in a 24-week randomized, double-blind, placebo-controlled trial of 3g n-3 polyunsaturated fatty acids (PUFA), a cohort of patients diagnosed with PsA by the CASPAR criteria. These patients had a mean age of 50.8, 57.8 % female and 100 % caucasian. Clinical variables and serum samples were collected at baseline and after 24 weeks of follow-up. An unpaired t-test was used for evaluation of healthy individuals and patients affected by PsA, while a paired t-test was used for evaluation of treatment at baseline and after 24 weeks.Results:A technically robust and specific assay was developed. The inter- and intra-assay variation of PROM was determined as 14% and 4 % respectively. PROM showed a good dilution recovery, spiking recovery, and storage /freeze-thaw stability (All, 100%±20%). PROM showed to be specific towards the targeted sequence, and did not show any reactivity towards the truncated peptide, elongated peptide or non-sense peptide. In the Discovery Cohort, serum levels of PROM were increased in patients with PsA compared to healthy individuals (p=0.032, Figure 1A). This increase was confirmed by the Validation Cohort, where PsA patients were significantly increased compared to healthy individuals at baseline (p=0.002, Figure 1B). After 24 weeks, the levels of PROM were unchanged in the n-3 PUFA treated group.Figure 1.Conclusion:The novel biomarker PROM, reflecting connective tissue remodeling, is elevated in PsA patients compared to healthy controls in two independent cohorts. No significant association was found for PROM in a low disease activity group of PsA patients treated with n-3 PUFA.References:NoneAcknowledgments:We thank the Innovation Foundation and Danish Research Foundation for providing funding for this study.Disclosure of Interests:Dovile Sinkeviciute Grant/research support from: Industrial PhD Student, Employee of: Industrial PhD Student, Annette Schlemmer: None declared, Erik Berg Schmidt: None declared, Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S., Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Jeppe Hagstrup Christensen: None declared, Salome Kristensen: None declared, Signe Holm Nielsen Employee of: Full time employee at Nordic Bioscience

Multi-cancer detection and tissue of origin determination based on 5-hydroxymethylcytosine biomarkers in circulating cell-free DNA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3123-3123
Author(s):  
Zhou Zhang ◽  
Wenju Chang ◽  
Jiabin Cai ◽  
Yijiu Ren ◽  
Qiancheng You ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Classification Model ◽  
Protein Markers ◽  
Training Set ◽  
Cell Free Dna ◽  
Free Dna ◽  
Cancer Types ◽  
Tissue Of Origin ◽  
Testing Set ◽  
Circulating Cell Free Dna

3123 Background: Early detection may reduce cancer mortality. Systematic screening programs are available only for a limited number of cancers (e.g., colorectal cancer). The majority of common cancers are detected after the onset of signs and symptoms, making treatment difficult or less effective. We describe here a multi-cancer epigenetic approach for simultaneous cancer detection of common cancers (̃70% of adult cancers) and determination of tissue of origin (TOO) using circulating cell-free DNA (cfDNA) from plasma. Methods: A total of 2241 cancer cases, including patients with newly diagnosed primary colorectal, gastric, esophageal, liver, lung, and breast cancer (stages I-III or equivalent) and 2289 non-cancer controls were recruited from participating hospitals in China. Study participants were randomly assigned into a training set (70%) and a testing set (30%), and patients were matched for cancer types and stages. Plasma samples were collected before radical treatment or surgery. The 5hmC-Seal, a highly sensitive chemical labeling technique, was used to profile genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA from ̃5mL of plasma per person, followed by the next-generation sequencing, data summarization at gene-level, and normalization. We applied the elastic net regularization to establish a predictive rule based on the multivariable logistic regression model for cancer detection in the training set as well as a multiclass classification model for determining TOO. The final solution for simultaneous cancer detection and TOO determination was established by integrating the 5hmC-based models and protein markers (e.g., AFP). Overall sensitivity and specificity were computed and reported in the testing set of 670 cancer cases and 686 non-cancer controls. Results: For the primary scenario (i.e., stages I-III or equivalent), at specificity of 95%, the overall sensitivity achieved 79.3% for detecting a cancer patient in all six cancer types in the testing set, except stage I lung cancer, for which the multi-cancer detection solution showed a sensitivity of 51%. Notably, for individuals with a negative result from conventional protein markers (e.g., AFP, CEA), the 5hmC-only models showed 67.6% sensitivity at 98.2% specificity in the testing set, representing significant improvement. In the testing set, among the 500 cancer patients who were detected from the multi-cancer detection solution, 435 patients were assigned a TOO; of those, 362 (83.2%) TOO were correctly determined. Conclusions: The 5hmC-Seal in cfDNA shows the potential as a non-invasive tool that could be integrated into a screening program for simultaneous detection of common cancers and TOO localization. This approach can be expanded to additional cancer types and is currently undergoing validation in prospectively recruited cohorts.

scholarly journals Albumin platelet product as a novel score for liver fibrosis stage and prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koji Fujita ◽  
Kazumi Yamasaki ◽  
Asahiro Morishita ◽  
Tingting Shi ◽  
Joji Tani ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Validation Cohort ◽  
Activity Grade ◽  
Fibrosis Stage ◽  
Strongly Correlated ◽  
The Novel ◽  
Training Cohort ◽  
Blood Examination ◽  
Retrospective Multicenter Study ◽  
Overall Mortality

AbstractFibrosis-4 index, a conventional biomarker for liver fibrosis stage, is confounded by age and hepatitis activity grade. The current retrospective multicenter study aimed to formulate the novel indices of liver fibrosis by mathematically combining items of peripheral blood examination and to evaluate ability of prognosis prediction. After a novel index was established in a training cohort, the index was tested in a validation cohort. Briefly, a total of 426 patients were enrolled in a training cohort. Albumin and platelet most strongly correlated to fibrosis stage among blood examination. Albumin platelet product (APP) = Albumin × platelet/1000 could differentiate the four stages of liver fibrosis (p < 0.05). APP indicated fibrosis stage independent from hepatitis activity grade. A cut-off value = 4.349 diagnosed cirrhosis with area under ROC more than 0.8. Multivariate analysis revealed that smaller APP independently contributed to HCC prevalence and overall mortality. The results were validated in another 707 patients with HCV infection. In conclusion, APP was not confounded by age or hepatitis activity grade contrary to Fibrosis-4 index. APP is as simple as physicians can calculate it by pen calculation. The product serves physicians in managing patients with chronic liver disease.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

Spanish Version of the Mini-Linguistic State Examination for the Diagnosis of Primary Progressive Aphasia

2021 ◽  
pp. 1-8
Author(s):  
Jordi A. Matias-Guiu ◽  
Vanesa Pytel ◽  
Laura Hernández-Lorenzo ◽  
Nikil Patel ◽  
Katie A. Peterson ◽  
...  
Keyword(s):  
Primary Progressive Aphasia ◽  
Spanish Version ◽  
Classification Model ◽  
Healthy Controls ◽  
Language Test ◽  
Cross Sectional ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Clinical Variants ◽  
State Examination

Background: Primary progressive aphasia (PPA) is a neurodegenerative syndrome with three main clinical variants: non-fluent, semantic, and logopenic. Clinical diagnosis and accurate classification are challenging and often time-consuming. The Mini-Linguistic State Examination (MLSE) has been recently developed as a short language test to specifically assess language in neurodegenerative disorders. Objective: Our aim was to adapt and validate the Spanish version of MLSE for PPA diagnosis. Methods: Cross-sectional study involving 70 patients with PPA and 42 healthy controls evaluated with the MLSE. Patients were independently diagnosed and classified according to comprehensive cognitive evaluation and advanced neuroimaging. Results: Internal consistency was 0.758. The influence of age and education was very low. The area under the curve for discriminating PPA patients and healthy controls was 0.99. Effect sizes were moderate-large for the discrimination between PPA and healthy controls. Motor speech, phonology, and semantic subscores discriminated between the three clinical variants. A random forest classification model obtained an F1-score of 81%for the three PPA variants. Conclusion: Our study provides a brief and useful language test for PPA diagnosis, with excellent properties for both clinical routine assessment and research purposes.

scholarly journals Radiomic nomogram based on MRI to predict grade of branching type intraductal papillary mucinous neoplasms of the pancreas: a multicenter study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sijia Cui ◽  
Tianyu Tang ◽  
Qiuming Su ◽  
Yajie Wang ◽  
Zhenyu Shu ◽  
...  
Keyword(s):  
Calibration Curve ◽  
Main Pancreatic Duct ◽  
Validation Cohort ◽  
External Validation ◽  
High Grade ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Training Cohort ◽  
Independent Validation ◽  
Medical Centers ◽  
Mucinous Neoplasms

Abstract Background Accurate diagnosis of high-grade branching type intraductal papillary mucinous neoplasms (BD-IPMNs) is challenging in clinical setting. We aimed to construct and validate a nomogram combining clinical characteristics and radiomic features for the preoperative prediction of low and high-grade in BD-IPMNs. Methods Two hundred and two patients from three medical centers were enrolled. The high-grade BD-IPMN group comprised patients with high-grade dysplasia and invasive carcinoma in BD-IPMN (n = 50). The training cohort comprised patients from the first medical center (n = 103), and the external independent validation cohorts comprised patients from the second and third medical centers (n = 48 and 51). Within 3 months prior to surgery, all patients were subjected to magnetic resonance examination. The volume of interest was delineated on T1-weighted (T1-w) imaging, T2-weighted (T2-w) imaging, and contrast-enhanced T1-weighted (CET1-w) imaging, respectively, on each tumor slice. Quantitative image features were extracted using MITK software (G.E.). The Mann-Whitney U test or independent-sample t-test, and LASSO regression, were applied for data dimension reduction, after which a radiomic signature was constructed for grade assessment. Based on the training cohort, we developed a combined nomogram model incorporating clinical variables and the radiomic signature. Decision curve analysis (DCA), a receiver operating characteristic curve (ROC), a calibration curve, and the area under the ROC curve (AUC) were used to evaluate the utility of the constructed model based on the external independent validation cohorts. Results To predict tumor grade, we developed a nine-feature-combined radiomic signature. For the radiomic signature, the AUC values of high-grade disease were 0.836 in the training cohort, 0.811 in external validation cohort 1, and 0.822 in external validation cohort 2. The CA19–9 level and main pancreatic duct size were identified as independent parameters of high-grade of BD-IPMNs using multivariate logistic regression analysis. The CA19–9 level and main pancreatic duct size were then used to construct the radiomic nomogram. Using the radiomic nomogram, the high-grade disease-associated AUC values were 0.903 (training cohort), 0.884 (external validation cohort 1), and 0.876 (external validation cohort 2). The clinical utility of the developed nomogram was verified using the calibration curve and DCA. Conclusions The developed radiomic nomogram model could effectively distinguish high-grade patients with BD-IPMNs preoperatively. This preoperative identification might improve treatment methods and promote personalized therapy in patients with BD-IPMNs.

scholarly journals 1358. Using natural language processing to optimize case ascertainment of acute otitis media in a large, state-wide pediatric practice network

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S690-S691
Author(s):  
Joshua C Herigon ◽  
Amir Kimia ◽  
Marvin Harper
Keyword(s):  
Natural Language Processing ◽  
Natural Language ◽  
Otitis Media ◽  
Language Processing ◽  
Validation Cohort ◽  
Recursive Partitioning ◽  
Acute Otitis Media ◽  
Clinical Documentation ◽  
Training Cohort ◽  
Icd Codes

Abstract Background Antibiotics are the most commonly prescribed drugs for children and frequently inappropriately prescribed. Outpatient antimicrobial stewardship interventions aim to reduce inappropriate antibiotic use. Previous work has relied on diagnosis coding for case identification which may be inaccurate. In this study, we sought to develop automated methods for analyzing note text to identify cases of acute otitis media (AOM) based on clinical documentation. Methods We conducted a cross-sectional retrospective chart review and sampled encounters from 7/1/2018 – 6/30/2019 for patients &lt; 5 years old presenting for a problem-focused visit. Complete note text and limited structured data were extracted for 12 randomly selected weekdays (one from each month during the study period). An additional weekday was randomly selected for validation. The primary outcome was correctly identifying encounters where AOM was present. Human review was considered the “gold standard” and was compared to ICD codes, a natural language processing (NLP) model, and a recursive partitioning (RP) model. Results A total of 2,724 encounters were included in the training cohort and 793 in the validation cohort. ICD codes and NLP had good performance overall with sensitivity 91.2% and 93.1% respectively in the training cohort. However, NLP had a significant drop-off in performance in the validation cohort (sensitivity: 83.4%). The RP model had the highest sensitivity (97.2% training cohort; 94.1% validation cohort) out of the 3 methods. Figure 1. Details of encounters included in the training and validation cohorts. Table 1. Performance of ICD coding, a natural language processing (NLP) model, and a recursive partitioning (RP) model for identifying cases of acute otitis media (AOM) Conclusion Natural language processing of outpatient pediatric visit documentation can be used successfully to create models accurately identifying cases of AOM based on clinical documentation. Combining NLP and structured data can improve automated case detection, leading to more accurate assessment of antibiotic prescribing practices. These techniques may be valuable in optimizing outpatient antimicrobial stewardship efforts. Disclosures All Authors: No reported disclosures

scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

Refining TNM-8 M1 categories with anatomic subgroups for previously untreated de novo metastatic nasopharyngeal carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6046-6046
Author(s):  
Sik-Kwan Chan ◽  
Cheng Lin ◽  
Shao Hui Huang ◽  
Tin Ching Chau ◽  
Qiaojuan Guo ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Nasopharyngeal Carcinoma ◽  
Bone Metastases ◽  
Validation Cohort ◽  
De Novo ◽  
Multivariable Analysis ◽  
Term Survival ◽  
Training Cohort ◽  
Study Results ◽  
Multivariable Analyses

6046 Background: The eighth edition TNM (TNM-8) classified de novo metastatic (metastatic disease at presentation) nasopharyngeal carcinoma (NPC) as M1 without further subdivision. However, survival heterogeneity exists and long-term survival has been observed in a subset of this population. We hypothesize that certain metastatic characteristics could further segregate survival for de novo M1 NPC. Methods: Patients with previously untreated de novo M1 NPC prospectively treated in two academic institutions (The University of Hong Kong [n = 69] and Provincial Clinical College of Fujian Medical University [n = 114] between 2007 and 2016 were recruited and re-staged based on TNM-8 in this study. They were randomized in 2:1 ratio to generate a training cohort (n = 120) and validation cohort (n = 63) respectively. Univariable and multivariable analyses (MVA) were performed for the training cohort to identify the anatomic prognostic factors of overall survival (OS). We then performed recursive partitioning analysis (RPA) which incorporated the anatomic prognostic factors identified in multivariable analyses and derived a new set of RPA stage groups (Anatomic-RPA groups) which predicted OS in the training cohort. The significance of Anatomic-RPA groups in the training cohort was then validated in the validation cohort. UVA and MVA were performed again on the validation cohorts to identify significant OS prognosticators. Results: The training and the validation cohorts had a median follow-up of 27.2 months and 30.2 months, respectively, with the 3-year OS of 51.6% and 51.1%, respectively. Univariable analysis (UVA) and multivariable analysis (MVA) revealed that co-existing liver and bone metastases was the only factor prognostic of OS. Anatomic-RPA groups based on the anatomic prognostic factors identified in UVA and MVA yielded good segregation (M1a: no co-existing liver and bone metastases and M1b: co-existing both liver and bone metastases; median OS 39.5 and 23.7 months respectively; P =.004). RPA for the validation set also confirmed good segregation with co-existing liver and bone metastases (M1a: no co-existing liver and bone metastases and M1b: co-existing liver and bone metastases), with median OS 47.7 and 16.0 months, respectively; P =.008). It was also the only prognostic factor in UVA and MVA in the validation cohort. Conclusions: Our Anatomic-RPA M1 stage groups with anatomical factors provided better subgroup segregation for de novo M1 NPC. The study results provide a robust justification to refine M1 categories in future editions of TNM staging classification.

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