Specific gene expression profiles are associated with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma

McLaren, Patrick J.; Barnes, Anthony P.; Terrell, Willy Z; Vaccaro, Gina M.; Wiedrick, Jack; Hunter, John G.; Dolan, James P.

doi:10.1016/j.amjsurg.2017.03.024

Cited by 13 publications

(12 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biomarker studies to date have been hampered by small patient numbers and authors frequently cited the inadequate powering of their studies as a fundamental limitation [ 49 , 52 , 61 , 90 ]. Incorporating small sample sizes relative to the number of gene expression measurements means that gene expression studies are vulnerable to overfitting, often due to failure to correct for multiple hypothesis testing [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…McLaren et al . also used FFPE endoscopic biopsies to evaluate the expression of 11 genes using RT–PCR [ 49 ]. Most treatment regimens involved platinum agents and 5-FU, although exact regimens varied significantly and the majority of studies assessed pathological response but utilized a variety of classification systems and cut-offs.…”

Section: Predictive Biomarkers In Oesophageal Cancermentioning

confidence: 99%

“…McLaren et al . preselected 11 candidate genes based on their association with oesophageal cancer prognosis and found that overexpression of CCL28 and underexpression of DKK3 were significantly associated with pathological complete response to neoadjuvant chemoradiotherapy [ 49 ]. CCL28 recruits T regulatory cells, is involved in regulation of the immune response, and was previously identified as being associated with chemotherapy response by Maher et al .…”

Section: Predictive Biomarkers In Oesophageal Cancermentioning

confidence: 99%

See 2 more Smart Citations

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

Lavery

Turkington

2020

Gastroenterology Report

View full text Add to dashboard Cite

Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%–30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Predictive Biomarkers In Oesophageal Cancermentioning

confidence: 99%

Section: Predictive Biomarkers In Oesophageal Cancermentioning

confidence: 99%

See 1 more Smart Citation

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

Lavery

Turkington

2020

Gastroenterology Report

View full text Add to dashboard Cite

show abstract

“…Gene CCL28 was overexpressed in pathologic complete response patients, and it could be a potential predictor of treatment response. 44 Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, plays an important role in the biosynthesis and tumor development of extracellular matrix protein; wild-type LOXL2 (LOXL2Δ72) significantly promotes esophageal squamous cells by upregulating CCL28 cancer ESCC cell migration. 45 …”

Section: Discussionmentioning

confidence: 99%

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips

Tong

Wang

et al. 2018

OTT

View full text Add to dashboard Cite

BackgroundThe diagnosis rate of early stage esophageal squamous cell carcinoma (ESCC) is low due to the lack of specific tumor markers. Seeking for these markers is beneficial to improve the early diagnosis rate and the prognosis of patients. This study profiles the differentially expressed proteins of early stage ESCC patients via the AAH-BLG-507 protein chip, which further consolidates the clinical evidence of ESCC diagnosis.Materials and methodsIn this study, 20 serum samples were collected from Taihe Hospital between August 2016 and June 2017. Ten of them carried ESCC, while the rest were healthy controls. To profile the proteins’ expression level, the AAH-BLG-507 protein chip was used, and both highly expressed and lowly expressed proteins were fished out. Meanwhile, their biological roles were examined by using Gene Ontology (GO) database and String database, and they were further verified by ELISA.ResultsResults showed that the expression levels of AXL, ARTN, Ang2, BDNF, BMP7, cripto-1, CCL28, E-selectin, IL-6, IL-8 and SHH in the serum of early ESCC were significantly upregulated (P<0.05), particularly IL-6 and IL-8. The expression levels of TSP1 and MMP-8 were markedly downregulated (P<0.05). Analysis showed that these proteins were mainly involved in angiogenesis, signal transduction, cell proliferation and migration, indicating the close relationship with the development of ESCC.ConclusionIt suggested that IL-6 and IL-8 proteins could be considered as the markers for ESCC diagnosis.

show abstract

“…No association with miRNAs or promoter methylation status was found while treatment of MB cells with Trichostatin A (TSA), a potent inhibitor of histone deacetylases (HDAC), was able to restore both DKK3 mRNA and protein (Valdora et al, ). Recently, it was also reported that DKK3 expression can work as a predictor of response to chemotherapy with the genes CCL28 and DKK3 being potential predictors of treatment response to neoadjuvant chemotherapy in esophageal cancer (McLaren et al, ). Moreover, it was included in the seven‐gene expression signature that was demonstrated to be an accurate predictor of clinical outcome in patients with ovarian cancer (Wang, Wang, Zhou, Yu, & Zhang, ).…”

Section: Introductionmentioning

confidence: 99%

Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers?

Hamzehzadeh

Caraglia

Atkin

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Wnt signaling is an evolutionary highly conserved pathway that is modulated by several inhibitors and activators, and plays a key role in numerous physiological processes. One of the extracellular Wnt inhibitors is the DKK (Dickkopf Homolog) family which has four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy). DKK3 is a divergent member of the DKK protein family. Evidence suggests that DKK3 may serve as a potential therapeutic target in several types of human cancers. We review here the biological role of DKK3 as a tumor suppressor gene (TSG) or oncogene, and its correlation with various miRNAs. In addition, we discuss the role of polymorphisms and promoter methylation of the DKK3 gene, and of its expression in regulating cancer cell proliferation. Finally, we propose that DKK3 may be considered as both a biomarker and a therapeutic target in different cancers.

show abstract

Specific gene expression profiles are associated with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma

Abstract: EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response.

Cited by 13 publications

References 29 publications

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips

Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers?

Contact Info

Product

Resources

About