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Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.

ABSTRACT: BACKGROUND:RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer. METHODS:RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data. RESULTS:While nuclear RBM3 expression was always high in benign esophageal epithelium, high RBM3 expression was only detectable in 66.4% of interpretable EACs and 59.3% of ESCCs. Decreased RBM3 expression was linked to a subset of EACs with advanced UICC stage and presence of distant metastasis (P?=?0.0031 and P?=?0.0024). In ESCC, decreased RBM3 expression was associated with advanced UICC stage, high tumor stage, and positive lymph node status (P?=?0.0213, P?=?0.0061, and P?=?0.0192). However, RBM3 expression was largely unrelated to survival of patients with esophageal cancer (EAC: P?=?0.212 and ESCC: P?=?0.5992). CONCLUSIONS:In summary, the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis.

SUBMITTER: Grupp K

PROVIDER: S-EPMC6233549 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.

Grupp Katharina K Hofmann Bianca B Kutup Asad A Bachmann Kai K Bogoevski Dean D Melling Nathaniel N Uzunoglu Faik Guntac FG El Gammal Alexander Tarek AT Koop Christina C Simon Ronald R Steurer Stefan S Krech Till T Burdak-Rothkamm Susanne S Jacobsen Frank F Sauter Guido G Izbicki Jakob J Wilczak Waldemar W

BMC cancer 20181112 1

<h4>Background</h4>RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer.<h4>Methods</h4>RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data.<h4>Results</h4>While ...[more]

PMID: 30419865

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Project description:The incidence of oesophageal adenocarcinoma (OeC) has been increasing rapidly in most Western countries during the last few decades. Although multimodal treatment combining pre-operative chemotherapy with radical surgical resection has become the standard of care in the UK for all patients with locally advanced resectable disease, the 5-year survival rate in this patient group is less than 25%. Only 30% of all patients will benefit from pre-operative chemotherapy. Hence, there is an urgent clinical need to identify genomic markers that allow stratification of patients for a more individualised therapy approach. The goal of this study is to use whole genome high-resolution array CGH to examine the DNA copy number profile of a subset of OeC patients recruited into the OE02 trial and establish it’s relationship with clinicopathological variables including pathological tumor regression and patient survival. High-resolution array CGH analysis was conducted on 84 formalin fixed paraffin embedded resection samples obtained from subjects enrolled in the Oe02 trial. We compared the DNA copy number profiles between patients treated with chemotherapy and surgery and those treated with surgery alone. DNA copy number entropy was assessed to identify differences in overall copy number aberrations between the two treatment groups. Furthermore, the association between DNA copy number aberrations and tumor regression grade was investigated. The genetic make-up of OeCs investigated in the current study proved to be highly complex reducing our ability to determine the background normal copy number level in a tumor sample. Using DNA copy number entropy as a measure to compare sample profiles, we identified significant treatment arm specific DNA copy number aberration patterns predominantly in chromosome 1 and 5. High DNA copy number entropy was associated with longer overall survival. Differential DNA copy number entropy was observed between the two treatment groups, and the positions of the driving DNA regions were identified. To our surprise, the differences between the treatment groups went unnoticed when a standard test was applied. We also found that the DNA copy number entropy was strongly correlated with patients’ overall survival and clinicopathological characteristics. To the best of our knowledge, this is the first study in OeC quantitatively showed that the tumor heterogeneity was reduced by chemotherapy. And, the observed tumor heterogeneity was shown to has prognostic value. However, further research is needed to narrow down these regions to a few driving genes/probes that may aid in predicting whether a new patient will benefit from chemotherapy.

Project description:Purpose The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin ?6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin ?6 in ESCC remain unknown. Methods To investigate the differential expression of integrin ?6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin ?6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan–Meier method, with significant variables further evaluated by multivariate Cox regression analyses. Results The expression of integrin ?6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin ?6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin ?6 and HAX-1. Furthermore, the expression of integrin ?6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin ?6 and high HAX-1 expression demonstrated worst outcomes. Conclusion The present findings suggested the predictive value of integrin ?6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin ?6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.

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Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.

Publications

Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.

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