Glucose transporter 1 expression as a marker of  prognosis in oesophageal adenocarcinoma

Blayney, Jaine K.; Cairns, Lauren; Li, Gerald; McCabe, Niamh; Stevenson, Leanne; Peters, Christopher J.; Reid, N.; Spence, Veronica J; Chisambo, Chintapuza; McManus, Damian; James, Jacqueline; McQuaid, Stephen; Craig, Stephanie G.; Arthur, Ken; McArt, Darragh G.; Ong, Chin-Ann Johnny; Lao‐Sirieix, Pierre; Hamilton, Peter; Salto-Tellez, Manuel; Eatock, Martin; Coleman, Helen; Fitzgerald, Rebecca C.; Kennedy, Richard D.; Turkington, Richard; Clinical, Oesophageal Cancer

doi:10.18632/oncotarget.24906

Cited by 13 publications

(18 citation statements)

References 42 publications

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“…Clinical data and information on study outcomes up until 31 December 2014 was retrieved via patient note review at the Northern Ireland Cancer Centre, as previously described [17]. Patient information included age at diagnosis, date of diagnosis, date of surgery, and patient sex.…”

Section: Clinical Datamentioning

confidence: 99%

“…The primary aim of this study is to investigate the potential association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival. A secondary aim was to investigate the impact of these lifestyle factors on survival, according to the expression of the selected biomarkers, P53, HER2, GLUT1, and CD8 which have been shown to be associated with prognosis in esophageal adenocarcinoma [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

McCain¹,

McManus

McQuaid³

et al. 2019

Cancer Causes Control

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Purpose To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. Methods A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. Results In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13-3.38) but not adjusted (HR 1.70 95% CI 0.95-3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. Conclusions In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival.

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Section: Clinical Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

McCain¹,

McManus

McQuaid³

et al. 2019

Cancer Causes Control

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“…However, elevated GLUT1 expression has been observed in many epithelial malignancies, and high GLUT1 levels have been reported to be a prognostic marker for esophageal cancer. 6 Analysis of datasets from The Cancer Genome Atlas confirmed that patients with head and neck squamous cell carcinoma with a favorable immune and metabolic gene signature (high CD8A, high COX5B and low GLUT1) had better short-term and long-term survival compared with patients with an unfavorable signature. 7 Positive GLUT1 expression has also been associated with tumor regression grade and may be a useful predictive marker for response to chemoradiotherapy in rectal cancer.…”

Section: Introductionmentioning

confidence: 90%

“…GLUT1 expression is normally restricted to erythrocytes, endothelial cells at the blood–brain barrier and the placenta, and it is generally absent from normal epithelial cells. However, elevated GLUT1 expression has been observed in many epithelial malignancies, and high GLUT1 levels have been reported to be a prognostic marker for esophageal cancer . Analysis of datasets from The Cancer Genome Atlas confirmed that patients with head and neck squamous cell carcinoma with a favorable immune and metabolic gene signature (high CD8A, high COX5B and low GLUT1) had better short‐term and long‐term survival compared with patients with an unfavorable signature .…”

Section: Introductionmentioning

confidence: 96%

Glucose transporter 1 regulates the proliferation and cisplatin sensitivity of esophageal cancer

et al. 2019

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Glucose transporter 1 ( GLUT 1) expression is a prognostic marker for esophageal squamous cell carcinoma ( ESCC ). Recent work on GLUT 1 and development of specific inhibitors supports the feasibility of GLUT 1 inhibition as a treatment for various cancers. The anti–proliferative effects of GLUT 1‐specific small interfering RNA (si RNA ) and a GLUT 1 inhibitor were evaluated in ESCC cell lines. Expression of pro–proliferative and anti–proliferative signaling and effector molecules was examined by western blotting and quantitative RT ‐ PCR . GLUT 1 expression in pretreatment clinical biopsy samples was measured by immunohistochemistry and correlated with various clinicopathological parameters and response to chemotherapy. The reduction in standardized uptake value ( SUV ) of 18 F‐fluoro‐deoxyglucose was calculated using the formula: ([pretreatment SUV max – posttreatment SUV max ]/pretreatment SUV max ) × 100. GLUT 1‐specific si RNA expression in ESCC cells inhibited their proliferation, increased expression of p27kip, and decreased expression of cyclin‐dependent kinase 6, pyruvate kinase muscle isozyme M2, lactate dehydrogenase A and phospho‐ ERK 1/2. Suppression of GLUT 1 by si RNA increased low‐dose cisplatin‐induced inhibition of proliferation of TE ‐11 ESCC cells, which express high GLUT 1 levels. Similarly, BAY ‐876, a GLUT 1 inhibitor, enhanced cisplatin‐mediated inhibition of ESCC cell proliferation. GLUT 1 expression in pretreatment biopsy samples was associated with the response to chemotherapy as well as the pathological tumor stage and histological response grade after esophagectomy. Finally, GLUT 1‐negative tumors showed a significantly larger reduction in SUV max (61.2% ± 4.5%) compared with GLUT 1‐positive tumors (46.2% ± 4.4%). GLUT 1 expression may be a surrogate marker of response to chemotherapy, and inhibition of GLUT 1 may be a potential novel therapy for ESCC patients.

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“…A detailed description of TMA construction methods within the Northern Ireland Biobank is given elsewhere. 21,22…”

Section: T I S S U E M I C R O a R R A Y ( T M A ) C O N S T R U C T mentioning

confidence: 99%

High PTGS2 expression in post‐neoadjuvant chemotherapy‐treated oesophageal adenocarcinoma is associated with improved survival: a population‐based cohort study

et al. 2019

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Aims High prostaglandin endoperoxide synthase‐2 (PTGS2) enzyme expression in oesophageal adenocarcinoma has been shown to independently predict poor prognosis; however, the evidence is inconsistent. The aim of this study was to investigated the association between PTGS2 expression and prognosis in patients with oesophageal adenocarcinoma. Methods and results A cohort of 135 patients with oesophageal adenocarcinoma who received neoadjuvant chemotherapy and surgery from 2004 to 2012 was identified in the Northern Ireland Cancer Centre. Tissue microarrays were created in the Northern Ireland Biobank, with triplicate cores being sampled from each tumour. Immunohistochemical PTGS2 expression was scored by two independent assessors, with intensity and proportion of tumour staining being used to calculate H‐scores for each patient. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer‐specific survival, and recurrence‐free survival by PTGS2 expression, with adjustment for potential confounders. Patients were followed up for a mean of 3.0 years (standard deviation 1.8 years). The PTGS2 expression cut‐off value was determined from the median H‐score of the cohort (270/300). High (n = 79), as compared with low (n = 56), PTGS2 expression was associated with improved cancer‐specific survival (adjusted HR 0.56, 95% CI 0.33–0.94; P = 0.03). PTGS2 expression was not significantly associated with recurrence‐free survival (adjusted HR 0.85, 95% CI 0.52–1.38; P = 0.51). Conclusions High PTGS2 expression in oesophageal adenocarcinoma tissue was associated with improved overall and cancer‐specific survival, in contrast to previous evidence. As this is the first study of its kind to include patients who had undergone neoadjuvant chemotherapy, further studies are needed to clarify these associations.

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Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma

Cited by 13 publications

References 42 publications

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

Glucose transporter 1 regulates the proliferation and cisplatin sensitivity of esophageal cancer

High PTGS2 expression in post‐neoadjuvant chemotherapy‐treated oesophageal adenocarcinoma is associated with improved survival: a population‐based cohort study

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