Correlation of Overall Survival With Gene Expression Profiles in a Prospective Study of Resectable Esophageal Cancer

2011 ◽  
Vol 10 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Sheela Rao ◽  
Lyndsey Welsh ◽  
David Cunningham ◽  
Robert H. te-Poele ◽  
Martin Benson ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
pp. 31113.1-31113.6
Author(s):  
Touraj Asvadi Kermani ◽  
◽  
Seyed Ziaeddin Rasihashemi ◽  
Hoseinpour Feyzi ◽  
Moein Hoseinpour Feyzi ◽  
...  

Background: Esophagectomy is performed in all patients with resectable esophageal cancer. Transthoracic-Laparoscopic Esophagectomy (TLE) is a minimally invasive method and considered to be the most appropriate method. In this study, we aim to evaluate and compare the perioperative outcome, and 1-year overall survival of TLE and Transhiatal Esophagectomy (THE) approaches. Methods: In this retrospective study, we reviewed the medical records of 108 patients with esophageal cancer undergoing TLE (n=44) or THE (n=64) between 2015 and 2018. The patients were followed for one year. The intraoperative and postoperative findings, as well as 1-year overall-survival, were compared between the two groups. Results: TLE compared to THE had a longer surgery duration (278.63±33.28 vs 223.28±33.99 min, P=0.001), a higher number of dissected lymph nodes (15.06±2.95 vs 10.21±2.58, P=0.001), less blood loss (345.45±178.76 vs 585.15±294.75 mL, P<0.001), and need for transfusion (20.5% vs 45.3%, P=0.006) during surgery as well as lower ICU stay (2.59±0.77 vs 3.90±0.83 days, P<0.001) and ward stay (8.77±0.96 vs 11.42±1.71 days, P<0.001). THE had somewhat higher complication than TLE, but with no significant differences. Conclusion: TLE had a similar rate of complication to THE approach, but with lower blood loss and lower ICU and hospital stay, it is a more appropriate method for esophagectomy.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 51-51
Author(s):  
Patrick James McLaren ◽  
Anthony P Barnes ◽  
Willy Z Terrell ◽  
Gina M. Vaccaro ◽  
Jack Wiedrick ◽  
...  

51 Background: Predicting prognosis in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to therapeutic response. In this study, we analyzed specific predictor genes expressed in tumor specimens from our institutional repository. Our aim was to determine if specific gene expression profiles are associated with pathologic complete response (pCR) after neoadjuvant chemo-radiotherapy (CRT). Methods: We investigated eleven genes identified from prior studies (CCL28, SPARC, S100A2, SPRR3, SIRT2, NOV, PERP, PAPSS2, DCK, DKK3, ALDH1) that have significant association with esophageal cancer progression. Patients with esophageal adenocarcinoma treated with neoadjuvant CRT followed by esophagectomy at our institution between January 2011 and July 2015 were included. Quantitative real-time polymerase chain reaction was conducted on pre-treatment biopsy specimens to determine gene expression. Patients were classified into two groups: 1) pCR and, 2) no or poor response (NR) after CRT based on final pathology report. An omnibus test using Mahalanobis distance was applied to evaluate overall genetic expression differences between groups. Log-rank tests compared the differential expression of individual genes. Results: 29 patients (11 pCR and 18 NR) were analyzed. Overall, gene expression profiles were significantly different between pCR and NR patients (p < 0.01). In particular, CCL28 was over-expressed in pCR (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3-was under-expressed in pCR patients (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). Conclusions: Esophageal adenocarcinoma patients with a pCR after neoadjuvant therapy have genetic profiles that are significantly different from typical NR profiles. In our population, the genes CCL28 and DKK3 are potential predictors of treatment response.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 389-389
Author(s):  
Kolja Eppert ◽  
Katsuto Takenaka ◽  
Björn Nilsson ◽  
Eric R Lechman ◽  
Vicki Ling ◽  
...  

Abstract Abstract 389 Normal hematopoiesis and acute myeloid leukemia (AML) are organized as hierarchies with stem cells, which possess extensive self-renewal and proliferative capacity, at the apex. Although there is definitive evidence from experimental models for the existence of leukemic stem cells (LSC) in some human leukemias, the relevance of LSC to human disease progression is still lacking. While chemotherapeutic treatment of AML patients typically results in disease remission, the majority of patients will eventually relapse and succumb to the disease, indicating that residual LSC are not eliminated by current treatment. We hypothesize that stem cell derived gene expression profiles may be more clinically relevant than those derived from examination of bulk leukemia samples. Here we show the clinical significance of novel stem cell related expression profiles derived from 25 functionally validated human leukemia stem cell populations and 6 normal hematopoietic stem cell populations. Little is currently known about the molecular regulatory networks that govern human LSC or hematopoietic stem cells (HSC). Therefore, we have carried out global mRNA gene expression profiling of FACS sorted subpopulations of cells enriched for human stem cells, progenitor cells and mature cells from 16 AML primary patient samples and 3 cord blood samples to investigate these pathways. Similar to normal hematopoietic stem cells, leukemia stem, progenitor and mature cells can be sorted using CD34 and CD38 markers. Due to the heterogeneous nature of AML, it is vital that quantitative functional assays are used to characterize the LSC and progenitor activity in each sorted fraction. In vitro cell suspension cultures and methylcellulose colony formation assays were performed to characterize progenitor and blast populations. Importantly, we applied a novel and improved in vivo SCID leukemia initiating cell assay to substantiate the presence of LSC activity in each sorted fraction of 16 AML patient samples. With this enhanced assay, LSC were detected in the expected CD34+/CD38- population. However, in the majority of AML samples, LSC were detected in at least one additional fraction, demonstrating the importance of functional validation when interpreting global gene expression profiles of sorted stem cell populations. LSC and HSC specific signatures were identified following a statistical analysis that compared fractions with stem cell activity against those without (25 LSC vs 29 non-LSC; 6 HSC vs 6 non-HSC). When applied to an independent gene expression data set from 160 cytogenetically normal AML samples, a 25 probe LSC signature was the strongest predictor of overall survival (p<0.0001, HR=2.6, 95%CI 1.8-4.0, median survival 236 vs 999 days; Figure 1a). Furthermore, the 225 probe HSC specific signature derived from normal cells also provided a strong predictor of survival (p<0.0001, HR=2.3, 95%CI 1.5-3.4, median survival 238 vs 741 days; Figure 1b). We queried the gene expression-based chemical genomic database Connectivity Map with the LSC-related gene list and found a negative correlation between the genes in the LSC profile and the expression of genes that are transcriptionally induced following treatment with common chemotherapeutic compounds such as doxorubicin, suggesting resistance to chemotherapy as one possible mechanism for the correlation of the stem cell signatures with survival. Together these data support the hypothesis that the biological determinants that underlie stemness in both normal and leukemic cells are predictors of poor outcome, and are potential targets for novel therapy. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Chengtao Sun ◽  
Xianfeng Cheng ◽  
Chaoyu Wang ◽  
Xi Wang ◽  
Bing Xia ◽  
...  

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy, however, specific tumor-associated genes and signaling pathways are yet to be deciphered. Differentially expressed genes (DEGs) were computed based on gene expression profiles from GSE32018, GSE56315, and The Cancer Genome Atlas (TCGA) DLBC. Overlapping DEGs were then evaluated for gene ontology (GO), pathways enrichment, DNA methylation, protein–protein interaction (PPI) network analysis as well as survival analysis. Seventy-four up-regulated and 79 down-regulated DEGs were identified. From PPI network analysis, majority of the DEGs were involved in cell cycle, oocyte meiosis, and epithelial-to-mesenchymal transition (EMT) pathways. Six hub genes including CDC20, MELK, PBK, prostaglandin D2 synthase (PTGDS), PCNA, and CDK1 were selected using the Molecular Complex Detection (MCODE). CDC20 and PTGDS were able to predict overall survival (OS) in TCGA DLBC and in an additional independent cohort GSE31312. Furthermore, CDC20 DNA methylation negatively regulated CDC20 expression and was able to predict OS in DLBCL. A two-gene panel consisting of CDC20 and PTGDS had a better prognostic value compared with CDC20 or PTGDS alone in the TCGA cohort (P=0.026 and 0.039). Overall, the present study identified a set of novel genes and pathways that may play a significant role in the initiation and progression of DLBCL. In addition, CDC20 and PTGDS will provide useful guidance for therapeutic applications.


Oncology ◽  
2007 ◽  
Vol 73 (5-6) ◽  
pp. 366-375 ◽  
Author(s):  
Tetsuo Ito ◽  
Eiji Tanaka ◽  
Tadashi Kadowaki ◽  
Takatsugu Kan ◽  
Motoshige Higashiyama ◽  
...  

2007 ◽  
Vol 14 (12) ◽  
pp. 3602-3609 ◽  
Author(s):  
Cuong Duong ◽  
Danielle M. Greenawalt ◽  
Adam Kowalczyk ◽  
Marianne L. Ciavarella ◽  
Garvesh Raskutti ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16013-16013
Author(s):  
A. Nickles Fader ◽  
S. A. Vaziri ◽  
L. Rojas-Espaillat ◽  
P. W. Faber ◽  
P. Elson ◽  
...  

16013 Background: CCL2, a determinant of macrophage infiltration in tumors, is expressed in normal human ovarian surface epithelium but silenced or down-regulated in ovarian adenocarcinomas (Br J Cancer 92:2024, 2005). We determined the association between quantitative expression of CCL2 with platinum-taxane based chemotherapy response and clinical outcome in patients with primary ovarian cancer. Methods: Tumor samples from chemotherapy-naïve patients with advanced serous ovarian adenocarcinoma were obtained at the time of primary cytoreductive surgery. Gene expression profiles using RNA extracted from tissue enriched for >90% tumor from 2 chemotherapy sensitive (CS) and 8 chemotherapy resistant (CR) patients were performed using the Illumina Sentrix Human-6 Expression Bead-Chip microarray. Gene expression was quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger patient cohort. Statistics were generated using Wilcoxon rank sum tests and Kaplan-Meier survival curves. Results: Clustering analysis of gene expression profiles identified several genes, including CCL2, that were differentially expressed between the CS and CR tumor specimens. Levels of CCL2 were significantly (p<.001) under-expressed in all 8 CR patient tumors as compared to the 2 CS tumors. Quantification of CCL2 gene expression in 9 CS and 16 CR tumors by RT-PCR demonstrated that CCL2 was significantly down-regulated in the CR tumors when compared to the CS tumors (p<.001). Using normalized PCR cycle threshold scores, 22 of the 25 tumors were correctly classified, i.e., 8/9 CS had low CCL2 expression (sensitivity = 89%) and 14/16 CR had high expression (specificity = 88%). For patients with low CCL2 expression, progression free survival was 12 months versus 18.6 months for those with high CCL2 expression (p=.05). Median overall survival (OS) was 20.8 months for patients with low CCL2 expression, while OS was not yet reached for those with high CCL2 levels (p=.01). Conclusions: Results demonstrate that expression of CCL2 correlates with response to chemotherapy and survival in patients with primary ovarian cancer. Expression of CCL2 may be a useful independent biomarker of response to treatment and clinical outcome. No significant financial relationships to disclose.


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