scholarly journals Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 943 ◽  
Author(s):  
Jeong Il Yu ◽  
Hee Chul Park ◽  
Jeeyun Lee ◽  
Changhoon Choi ◽  
Won Ki Kang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemoradiotherapy ◽  
Recurrence Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Rna Analysis ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Independent Variable ◽  
Formalin Fixed

Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21–3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31–3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.

scholarly journals Protein Classification of Diffuse-Type Gastric Cancer Using Formalin-Fixed Paraffin-Embedded Samples

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 224s-224s
Author(s):  
W. Huang ◽  
X. Xia ◽  
J. Gao ◽  
Z. Li ◽  
S. Ge ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rna Processing ◽  
Protein Classification ◽  
Diffuse Type ◽  
Proteome Profiling ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Diffuse Type Gastric Cancer ◽  
Formalin Fixed

Background: Gastric cancer (GC) is the third leading cause of cancer deaths in the world. It is highly heterogeneous. Many molecular therapies for GC have entered clinical trials but, apart from trastuzumab, apatinib and ramucirumab, all have failed. One important reason is that insufficient attention is paid to the underlying subtypes and characteristics of GC, especially the diffuse-type gastric cancer (DGC) according to the Lauren classification with worst clinical outcomes. Aim: Here we firstly investigated formalin-fixed paraffin-embedded (FFPE) samples of DGC to establish clinically relevant molecular classification based on proteomics analysis. Also, we tried to generate a suitable classifier of DGC that can guide patient therapy. Methods: We screened a total of 2548 cases retrospectively, who underwent GC resection at Beijing Cancer Hospital from October 2006 to December 2011. We used a fast mass spectrometry workflow for proteome profiling. Finally we carried out proteome profiling of 99 DGC paired tumor-nearby tissues from FFPE sections. Median overall survival of the whole population was 55.0 months. Proteome profiling data from these samples were used to develop a subtype prediction model. We used consensus clustering to identify molecular subtypes based on differentially expressed proteins. The pathway enrichment was performed by GSEA, and the prediction classifier was generated by elastic-net machine learning. Kaplan-Meier survival analysis and Cox regression multivariate analysis were used. Results: A total of 8201 gene products were identified in this study, and 1249 differential expressed proteins between tumor and nearby-normal tissue was detected (FDR q-value < 0.01 by SAM). Tumor upregulated proteins mostly enriched into pathways including RNA processing, epithelial-mesenchymal transition (EMT), immune response and inflammation related pathways. Tumor downregulated proteins mostly enriched into metabolic pathways such as oxidative phosphorylation pathway. Based on proteome profiling alone, DGC can be subtyped into 3 major classes (PX1-3) that exhibit distinct proteome features and correlate with distinct clinical outcomes. PX1 (31 patients) exhibits RNA processing proteins and associates with the best prognosis; PX2 (26 patients) exhibits highly expressed cell cycle features, and the patients have poorer prognosis than those with cluster1 but better prognosis than those with cluster3; PX3 (42 patients) features EMT and the worst prognosis. We built a classifier of 12 marker proteins that can stratify DGC patients into these 3 subtypes, opening a door for protein classification in clinical application and intervention. Conclusion: Our study demonstrated that proteome profiling alone from FFPE samples was able to subtype DGC into 3 protein subtypes that were linked to distinct patterns of molecular alterations and prognosis. The prediction model need to be further verified in more clinical cohorts.

NY-ESO-1 as a predictive and prognostic marker in NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17539-e17539
Author(s):  
Tom John ◽  
Prudence Russell ◽  
Stephen Barnett ◽  
Zoe Wainer ◽  
Shane White ◽  
...  
Keyword(s):  
Predictive Marker ◽  
Curative Surgery ◽  
Cancer Testis Antigens ◽  
N2 Disease ◽  
Formalin Fixed Paraffin ◽  
Significant Survival ◽  
Formalin Fixed Paraffin Embedded ◽  
Iiia Nsclc ◽  
Formalin Fixed ◽  
Mutation Profiling

e17539 Background: Cancer-testis antigens (CTAgs) have previously been shown to be markers of poor prognosis and to be associated with chemoresistance in short interference RNA screens. In contradistinction, we recently reported the CTAg NY-ESO-1 predicted improved responses to neoadjuvant chemotherapy in pathological stage IIIA NSCLC. Despite this, no significant survival benefit was seen in NY-ESO-1 positive (NY-ESO-1+) patients. Given that tissues available for staining in the neoadjuvant setting were limited, we investigated a retrospective cohort of patients who underwent curative surgery for pathological N2 disease. As some of these patients were operated on prior to the broad acceptance of adjuvant chemotherapy (ACT), half did not receive chemotherapy. We investigated NY-ESO-1 as a prognostic and/or predictive marker in these patients. Methods: Formalin fixed paraffin embedded tissues were reviewed and stained using standard methods for a panel of CTAgs including NY-ESO-1 by immunohistochemistry. Tumors were categorized as NY-ESO-1+ or NY-ESO-1-. Isolated DNA was subjected to mutation profiling using Sequenom’s MassArray platform. Molecular markers were correlated with clinicopathological features and survival. Results: NY-ESO-1 stained 26/104 (25%) samples, including 15 cases that received ACT and 11 that did not. NY-ESO-1+ tumors were enriched for squamous cell carcinomas over adenocarcinomas (12/29 vs. 8/57; p = 0.01). They also lacked EGFR mutants and were enriched for KRAS mutants amongst adenocarcinomas relative to NY-ESO-1- tumors (5/8 vs. 9/49; p=0.02). NY-ESO-1+ patients who did not receive ACT had significantly worse outcome than NY-ESO-1- patients who did not receive ACT (HR 2.66 1.2-5.86, p=0.01). Median survival favored NY-ESO-1+ patients who received chemotherapy (37.7 months) compared to NY-ESO-1- patients regardless of chemotherapy (28.2 ACT vs 15.7 No ACT; p= 0.25) and NY-ESO-1+ patients who did not receive ACT (7.75). Conclusions: In this dataset, NY-ESO-1 was poorly prognostic but also predictive for more favorable outcomes with chemotherapy. These data support our previous observation of increased responses to chemotherapy in NY-ESO-1+ N2 patients and warrant further study.

Genetic Activation of the MET Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric Cancer

2011 ◽  
Vol 29 (36) ◽  
pp. 4789-4795 ◽  
Author(s):  
Francesco Graziano ◽  
Nadia Galluccio ◽  
Paola Lorenzini ◽  
Annamaria Ruzzo ◽  
Emanuele Canestrari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Quantitative Polymerase Chain Reaction ◽  
Disease Free Survival ◽  
Copy Number Gain ◽  
Free Survival ◽  
Prognostic Effect ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Purpose To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. Patients and Methods A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). Results In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. Conclusion In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.

scholarly journals MicroRNA profiling of gastric cancer patients from formalin-fixed paraffin-embedded samples

2011 ◽  
Vol 2 (4) ◽  
pp. 613-619 ◽  
Author(s):  
SOSHI OSAWA ◽  
YUTAKA SHIMADA ◽  
SHINICHI SEKINE ◽  
TOMOYUKI OKUMURA ◽  
TAKUYA NAGATA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Microrna Profiling ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Gastric Cancer Patients ◽  
Formalin Fixed

scholarly journals RNA analysis of cancer predisposing genes in formalin-fixed paraffin-embedded tissue determines aberrant splicing

2018 ◽  
Vol 26 (8) ◽  
pp. 1143-1150 ◽  
Author(s):  
Anne ML Jansen ◽  
Heleen M van der Klift ◽  
Marieke AE Roos ◽  
Jaap DH van Eendenburg ◽  
Carli MJ Tops ◽  
...  
Keyword(s):  
Aberrant Splicing ◽  
Rna Analysis ◽  
Formalin Fixed Paraffin ◽  
Predisposing Genes ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

scholarly journals Prognostic Value of Postoperative Neutrophil and Albumin: Reassessment One Month After Gastric Cancer Surgery

2021 ◽  
Vol 11 ◽  
Author(s):  
Ali Guner ◽  
Minah Cho ◽  
Yoo-Min Kim ◽  
Jae-Ho Cheong ◽  
Woo Jin Hyung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Neutrophil Count ◽  
Prognostic Value ◽  
Risk Groups ◽  
Cancer Surgery ◽  
Recurrence Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Pathologic Stage

ObjectiveThe prognostic value of postoperative parameters reflecting the inflammatory and nutritional status of patients undergoing cancer surgery has been rarely studied. This study investigated the prognostic value of inflammatory and nutritional parameters measured preoperatively and 1 month after curative gastrectomy for gastric cancer.MethodsData from a prospectively maintained database of 1,194 patients with gastric cancer who underwent curative surgery in 2009–2018 were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative data, survival data, and laboratory parameters were extracted. Neutrophil counts, lymphocyte counts, and albumin levels before surgery and 1 month postoperatively were analyzed.ResultsIn multivariable analysis adjusted for age, sex, and pathologic stage, high neutrophil count (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.01–1.17, p = 0.022) and low albumin (HR 0.45, 95% CI 0.27–0.74, p = 0.002) 1 month postoperatively were independent prognostic factors for overall survival. High neutrophil count (HR 1.09, 95% CI 1.02–1.16, p = 0.015) 1 month postoperatively was also an independent prognostic factor for recurrence-free survival after adjusting for age, sex, body mass index, extent of gastrectomy, and pathologic stage. Patients were classified into risk groups based on thresholds of 4.2 × 103 cells/mm3 and 4.1 g/dl for 1-month neutrophil count and albumin. High-risk groups had a significantly worse prognosis than low-risk groups for overall survival (HR 5.87, 95% CI 3.28–10.51, p &lt;0.001) and recurrence-free survival (HR 1.52, 95% CI 1.07–2.16, p = 0.021).ConclusionsNeutrophil count and albumin level 1 month after curative surgery reflect long-term prognosis better than preoperative values. These parameters can be used to stratify patients with the same stage into different prognostic groups.

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