Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.

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Serum microRNAs to predict the response to nivolumab in patients with esophageal squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14511 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14511-e14511 ◽

Cited By ~ 1

Author(s):

Kazuki Sudo ◽

Ken Kato ◽

Juntaro Matsuzaki ◽

Junpei Kawauchi ◽

Satoko Takizawa ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Squamous Cell ◽

Phase Ii Study ◽

Progression Free Survival ◽

Free Survival ◽

Linear Discriminant ◽

Expression Levels

e14511 Background: A phase II study demonstrated that nivolumab (Nivo), a PD-1 inhibitor, had a meaningful activity for patients with esophageal squamous cell carcinoma. Although several biomarkers, including PD-L1 expression levels in tumor tissue, are explored to predict the efficacy of Nivo, further investigation is needed. Here we evaluated whether serum levels of microRNA (miRNA) could be a candidate of predictive markers. Methods: Among 65 patients who participated in the phase II study (JapicCTINo.142422) and received Nivo 3 mg/kg IV Q2W, 19 patients were treated at our institution. Patients were classified into responder and non-responder by investigators based on modified ir-RECIST. Serum samples were stored before and during treatment in the National Cancer Center Biobank. Comprehensive miRNA microarray analyses were performed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.), which was designed to detect 2565 miRNA expression levels. miRNA were compared between responders and non-responders using Fisher’s linear discriminant analysis, and then we calculated the area under curve (AUC) values of receiver operating characteristic curve. We explored the miRNA that showed AUC values of more than 0.8 and difference by 0.5 in the average log2 value of miRNA levels (log2miRNA) between responders and non-responders, and investigated their relation to progression-free survival using Kaplan-Meier curves and log-rank tests. Results: Among 19 patients, 5 responded (CR/PR, 1/4) to Nivo. We identified 3 miRNAs in the serum before treatment that were related to response to Nivo with AUC of 0.84 (log2miRNA of non-responder/responder: 13.16/12.47), 0.90 (8.65/10.20) and 0.81 (7.18/6.57), respectively. In the serum after the first treatment, 5 miRNAs were related to response to Nivo with AUC of 0.93 (11.93/11.09), 0.93 (11.87/11.13), 0.85 (7.92/8.53), 0.92 (6.61/5.82) and 0.93 (7.77/ 7.09), respectively. Among these 8 miRNAs, 4 miRNAs were significantly associated with progression-free survival. Conclusions: We identified miRNA candidates that could predict the response to Nivo. Further validation is warranted to confirm the results of our explorative research.

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