243 PROGNOSTIC IMPACT OF CXCR7 AND CXCL12 EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
High Expression ◽  
Average Score ◽  
Prognostic Impact ◽  
Cell Trafficking ◽  
Multiple Cancer ◽  
Cxcl12 Expression ◽  
Potential Biomarker

Abstract   Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.

High Expression of the ETS Transcription Factor ERG Predicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults

2006 ◽  
Vol 24 (29) ◽  
pp. 4714-4720 ◽  
Author(s):  
Claudia D. Baldus ◽  
Thomas Burmeister ◽  
Peter Martus ◽  
Stefan Schwartz ◽  
Nicola Gökbuget ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Real Time ◽  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
High Expression ◽  
Prognostic Impact ◽  
Free Survival ◽  
Molecular Aberrations

Purpose In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL. Patients and Methods ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG′s median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR. Results High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS. Conclusion High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.

scholarly journals Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Functional Enrichment ◽  
Prognostic Impact ◽  
Clinical Value ◽  
Immune Infiltration ◽  
Potential Biomarker

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.

scholarly journals A-kinase interacting protein 1, a potential biomarker associated with advanced tumor features and CXCL1/2 in prostate cancer

2020 ◽  
Vol 35 (2) ◽  
pp. 74-81
Author(s):  
Danlan Wang ◽  
Yuanfang Luo ◽  
Yonglian Guo ◽  
Guohao Li ◽  
Fan Li
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
High Expression ◽  
Interacting Protein ◽  
Free Survival ◽  
T Stage ◽  
Potential Biomarker ◽  
Disease Free ◽  
Cxcl1 Expression

Objective: This study aimed to investigate the correlation of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand 1 (CXCL1) and CXCL2, as well as their associations with clinical characteristics and prognosis in prostate cancer patients. Methods: A total of 248 eligible prostate cancer patients who underwent surgery were consecutively recruited, and tumor tissues were collected during the surgery. AKIP1, CXCL1, and CXCL2 expression in tumor tissues were assessed by immunohistochemistry. Disease-free survival and overall survival were recorded, and the median follow-up time was 27 months. Results: The proportion of patients with AKIP1, CXCL1, and CXCL2 high expression was 56.5%, 63.7%, and 56.9%, respectively. Additionally, AKIP1 expression positively correlated with CXCL1 expression ( P<0.001) and CXCL2 expression ( P<0.001), and CXCL1 expression was positively associated with CXCL2 expression ( P<0.001). Furthermore, AKIP1 expression positively correlated with pathological T stage ( P<0.001) and pathological N stage ( P=0.003). CXCL1 expression was positively associated with pathological T stage ( P<0.001) and pathological N stage ( P<0.001) as well. However, the CXCL2 expression only positively correlated with pathological T stage ( P=0.002). Also, AKIP1 high expression correlated with worse disease-free survival ( P=0.049) and OS ( P=0.013), and CXCL1 high expression was associated with unfavorable disease-free survival ( P=0.023) but not overall survival ( P=0.052). CXCL2 expression was not correlated with disease-free survival ( P=0.083) or overall survival ( P=0.065). Multivariate Cox’s regression disclosed that AKIP1 high expression independently predicted worse overall survival ( P=0.009). Conclusion: AKIP1 positively associates with CXCL1/2 and is a potential biomarker for disease monitoring as well as prognosis in prostate cancer.

Prolonged neutrophilia is associated with worse outcomes after Esophagectomy

2021 ◽  
Author(s):  
Ian C Bostock ◽  
Nicolas Zhou ◽  
Mara B Antonoff ◽  
Mariela Blum Murphy ◽  
Steven Lin ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Neoadjuvant Treatment ◽  
Multivariable Analysis ◽  
Distant Recurrence ◽  
Oncologic Outcomes ◽  
P Value ◽  
Salvage Procedure ◽  
Potential Biomarker ◽  
Complete Blood Counts ◽  
Biomarker Research

Abstract Neutrophilia is a potential biomarker for postoperative complications and oncologic outcomes. There is a paucity of data regarding neutrophilia in patients with esophageal adenocarcinoma. Our Institutional Database was queried for esophageal adenocarcinoma patients who underwent esophagectomy from 2006 to 2019. Complete blood counts (CBC), demographic characteristics, perioperative and oncologic outcomes were evaluated. Two groups were created based on the presence of prolonged neutrophilia (PN, &gt;7,000 absolute neutrophils 90 days after surgery). Univariate, multivariable, and survival analysis were performed (P-value &lt; 0.05). We identified 686 patients with complete CBC data: 565 in the no prolonged neutrophilia (NPN) and 121 in the PN groups (17.6%). The mean age was 54 versus 48 years in the NPN and PN groups (P = 0.01). There was no difference in height, weight, gender, race, tumor size, histology, pTNM, PS, ASA, salvage procedure, neoadjuvant treatment and comorbidities. On multivariable analysis, the PN group had increased transfusions (19.8% vs. 11.9%; P = 0.02), aspiration (13.2% vs. 2.5%; P = 0.002), pulmonary embolus (3.3% vs. 0.4%; P = 0.02), cardiac arrest (5% vs. 0.4%; P = 0.02) and hematologic complications (23.1% vs. 12.6%; P = 0.01). After controlling for any postoperative complication, PN had increased distant recurrence (24% vs. 12.7%; hazard ration [HR]: 2.3, 95% confidence interval [CI] 1.42–3.9; P = 0.001) and decreased OS (33.8% vs. 49.7%, HR: 1.83, 95% CI: 1.19–2.81; P = 0.006); median follow up 77 months (46–109). PN was predictive of distant recurrence and decreased overall survival. Further work investigating these neutrophil populations represents a potential area for biomarker research, immunomodulation, and may guide postoperative surveillance strategies.

Prognostic Impact of CXCR7 and CXCL12 Expression in Patients with Esophageal Adenocarcinoma

2021 ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Jonathan C. Yeung ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Prognostic Impact ◽  
Cxcl12 Expression

scholarly journals Prognostic Impact of Body Mass Index Stratified by Smoking Status in Patients With Esophageal Adenocarcinoma

2011 ◽  
Vol 29 (34) ◽  
pp. 4561-4567 ◽  
Author(s):  
Harry H. Yoon ◽  
Mark A. Lewis ◽  
Qian Shi ◽  
Maliha Khan ◽  
Stephen D. Cassivi ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Esophageal Adenocarcinoma ◽  
Body Mass ◽  
Cox Regression ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Prognostic Impact ◽  
Free Survival ◽  
Never Smokers

Purpose Given that smoking affects body mass index (BMI) and survival, stratification by smoking status may be required to determine the true prognostic impact of BMI. Although obesity increases risk for developing esophageal adenocarcinoma (EAC), the prognostic influence of obesity and its potential modification by smoking status is unknown in this disease. Patients and Methods All patients (N = 778) underwent potentially curative esophagectomy. BMI was calculated using measured height and weight at surgery and categorized as obese (≥ 30 kg/m2), overweight (25 to 29.9 kg/m2), or normal (18.5 to 24.9 kg/m2). Cigarette smoking was categorized as never or ever. The association of BMI with disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) was determined by Cox regression. Results Excess BMI was significantly associated with DSS in a manner that differed substantially by smoking status (P for interaction = .023). Among never smokers, obesity was significantly associated with adverse DSS (hazard ratio [HR] = 2.11; 95% CI, 1.31 to 3.43; P = .002), DFS (HR = 2.03; 95% CI, 1.30 to 3.18; P = .002), and OS (HR = 1.97; 95% CI, 1.24 to 3.14; P = .004), as compared with normal weight, after adjusting for covariates. By contrast, among ever smokers, obesity was not prognostic, and overweight status was significantly associated with favorable survival in univariate, but not multivariate, analysis. Conclusion Obesity among never smokers was independently associated with two-fold worsening of DSS, DFS, and OS after surgery for EAC, after adjusting for known prognostic factors. These data, in one of the largest reported resected EAC cohorts, are the first to show an adverse prognostic impact of obesity in EAC.

scholarly journals CD37 high expression as a potential biomarker and association with poor outcome in acute myeloid leukemia

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Qi Zhang ◽  
Qi Han ◽  
Jie Zi ◽  
Chunhua Song ◽  
Zheng Ge
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Analysis Data ◽  
High Expression ◽  
Cycle Phase ◽  
Potential Biomarker ◽  
Acute Myeloid

Abstract Background: CD37, a member of the transmembrane 4 superfamilies (TM4SF), has been proved to be abnormally expressed in a range of malignancies. Herein, we investigate the effects of CD37 expression and analyze its clinical outcome in acute myeloid leukemia (AML) patients. Methods: The RNA-seq and clinical data of AML patients were obtained from cBioPortal database. CD37 correlated genes, the expression prolife and survival curve of eight key genes were acquired from Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN. Pathway enrichment and protein–protein interaction (PPI) network analysis were performed based on metascape databases. Results: Our results showed that CD37 mRNA expression level was significantly up-regulated in patients with AML compared with healthy persons. Patients with high CD37 expression had shorter overall survival (OS) and disease-free survival (DFS). Pathway analysis data showed that CD37 is involved in DNA replication, RNA transport, Salmonella infection, ribonucleoprotein complex biogenesis, cell cycle phase transition and so on. Furthermore, we found eight genes correlated with CD37 are all highly expressed in AML patients, and high expression is associated with poor prognosis. Conclusion: Our study described systematical expression profiles and the prognostic values of CD37 in AML; our data suggested CD37 might be novel therapeutic target and promising prognostic biomarker in the patients.

scholarly journals Expression and prognostic impact of FZDs in pancreatic adenocarcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Li ◽  
Zirong Liu ◽  
Yamin Zhang
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Pancreatic Adenocarcinoma ◽  
Multivariable Analysis ◽  
Wnt Signaling Pathway ◽  
Small Sample ◽  
High Expression ◽  
Prognostic Impact ◽  
Expression Levels ◽  
High Expression Group

Abstract Background Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. Methods PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan–Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. Results In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/β-catenin pathway.

Association of KMT2C mutations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2600-2600
Author(s):  
Chunling Liu ◽  
Qianqian Duan ◽  
Qin Zhang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Multiple Cancer ◽  
Multiple Tumor ◽  
Potential Biomarker ◽  
Chinese Cohort ◽  
Pan Cancer

2600 Background: The KMT2 (lysine methyltransferase) family of histone modifying proteins play important roles in regulating developmental pathways, and mutations in the genes encoding these proteins have been strongly linked to many solid tumor cancers. Recently, there is emerging evidence that KMT2 family genes are involved in sensitivity to immune checkpoint inhibitors (ICIs) by modulating the immune environment. Here we explored the relationship between KMT2C mutation and its efficacy of immunotherapy. Methods: 1661 patients with next-generation sequencing (NGS) and immunotherapy data obtained from MSKCC clinical cohort were used to explore the association with KMT2C mutation and TMB and efficacy of ICIs. TMB was defined as the total number of somatic nonsynonymous mutations in the coding region. NGS data of 6624 pan-cancer patients who also detected MSI and PD-L1 expression from the Chinese clinical dataset were also analyzed relevance of mutation and these immune-related indicators. Results: In total, 9.81% (163/1661) patients in MSKCC cohort harbored KMT2C mutation. In the Chinese cohort, the KMT2C mutation ratio (11.19%, 741/6624) was similar to MSKCC. The TMB level of KMT2C mutation group in both MSKCC cohort and Chinese pan-cancer patient cohort was significantly higher than wild-type group (P < 0.001). A multivariable analysis across the pan-cancer cohort using Cox proportional-hazards regression demonstrated that KMT2C mutation was significantly associated with better OS (hazard ratio, 0.69; 95%CI, 0.52-0.90; P = 0.006), and association remained significant with bladder (P = 0.039), colorectal (P = 0.024), melanoma (P < 0.001) and renal (P < 0.001), adjusting for cancer age, sex, metastases or primary. In addition, in Chinese cohort, KMT2C mutation was associated with higher PD-L1 positive expression (≥1%) (P = 0.01203) and MSI-H (P < 0.001). Conclusions: KMT2C mutation shows impressive association with efficacy of ICIs. Meanwhile, KMT2C-mutant group has a higher TMB, PD-L1 expression and MSI-H. These results indicated that KMT2C mutation may serve as a good potential biomarker of ICI benefit in patients with multiple cancer types.

scholarly journals High-expression of LncRNA MAFG-AS1 is associated with the prognostic of patients with colorectal cancer

2020 ◽  
Vol 66 (11) ◽  
pp. 1530-1535
Author(s):  
Weichun Cui ◽  
Yong Wang ◽  
Xiangji Shen ◽  
Xudong Wu ◽  
Hui Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Expression ◽  
Rank Test ◽  
Depth Of Invasion ◽  
Chi Square ◽  
Potential Biomarker ◽  
Chi Square Test

SUMMARY OBJECTIVE: Long noncoding RNAs (lncRNAs) have been proven to exhibit distinct functions on the convoluted processes of tumor developments. Some studies on the biological functions of lncRNA MAFG-AS1 (MAFG-AS1) in cancers revealed that they may serve as an oncogene in some kinds of tumors, including colorectal cancer (CRC). However, little is known about the role of MAFG-AS1 in the prognostic of CRC. METHODS: A public dataset was mined for the screening of dysregulated lncRNAs in CRC. Quantitative real-time reverse transcription-polymerase chain reaction(qPCR) was used to compare the levels of MAFG-AS1 between paired MAFG-AS1 specimens and normal adjacent tissues. The correlations between MAFG-AS1 and clinic pathological features in CRC were analyzed using the chi-square test. The log-rank test and Kaplan-Meier test were carried out to compare the survival time of patients with high and low expressions of MAFG-AS1. Cox regression was applied for univariate and multivariate assays to validate whether MAFG-AS1 could be an independent factor in the prognosis of CRC. RESULTS: We found that the distinct upregulation of MAFG-AS1 in various tumors was a common event. MAFG-AS1 was distinctly up-regulated in CRC specimens compared to matched non-tumor specimens (p < 0.01). High MAFG-AS1 expressions were closely associated with depth of invasion (p = 0.011) and TNM stage (p = 0.022). Survival assays revealed that patients with high expression of MAFG-AS1 have a shorter overall survival (p = 0.0030) and disease-free survival (p = 0.0002). CONCLUSIONS: MAFG-AS1 can serve as a novel potential biomarker to predict CRC patients’ survival time.

Sign in / Sign up

Export Citation Format

Share Document