Soluble PD-L1 Concentration Is Proportional to the Expression of PD-L1 in Tissue and Is Associated with a Poor Prognosis in Esophageal Squamous Cell Carcinoma

Oncology ◽  
2021 ◽  
Vol 100 (1) ◽  
pp. 39-47
Author(s):  
Tadashi Shiraishi ◽  
Takeshi Toyozumi ◽  
Haruhito Sakata ◽  
Kentaro Murakami ◽  
Masayuki Kano ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laboratory Data ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Specimen ◽  
Expression Levels ◽  
Worse Prognosis

<b><i>Introduction:</i></b> We determined the soluble programmed cell death-1 ligand-1 (sPD-L1) concentration in patients with esophageal squamous cell carcinoma (ESCC), and confirmed the PD-L1 expression in resected specimens. <b><i>Methods:</i></b> Blood samples were collected from 73 patients with histologically proven ESCC. The serum levels of sPD-L1 were measured using an enzyme-linked immunosorbent assay. The correlations between the sPD-L1 concentration and the expression of PD-L1 in tumor specimens and tumor depth, lymph node metastasis, disease stage, and various laboratory data were assessed. <b><i>Results:</i></b> sPD-L1 levels in patients with high PD-L1 expression levels in tumor tissue were significantly higher than in patients with low PD-L1 expression levels (<i>p</i> = 0.042). The OS of the sPD-L1-high group was significantly worse than that of the low group (<i>p</i> = 0.028). Similarly, patients in whom a tissue specimen was PD-L1-positive group showed significantly poorer OS. <b><i>Conclusion:</i></b> The sPD-L1 concentration was correlated with the PD-L1 expression in tissues. Patients with PD-L1-positive tissue specimens showed significantly higher sPD-L1 levels in comparison to PD-L1-negative cases. Furthermore, patients with high sPD-L1 expression levels had a significantly worse prognosis than those with low sPD-L1 expression levels, and patients with a PD-L1-positive tissue specimen had a significantly worse prognosis than patients in whom the tissue specimen showed a low PD-L1 expression level.

scholarly journals Immunosuppressive phenotype of esophagus tumors stroma

2020 ◽  
Author(s):  
Alexei Gratchev ◽  
Olga V. Kovaleva ◽  
Madina A. Rashidova ◽  
Daria V. Samoilova ◽  
Valeria V. Mochalnikova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Immunohistochemical Analysis ◽  
Good Prognosis ◽  
Disease Stage ◽  
Rank Test ◽  
Esophageal Tumors

Abstract Background Tumor associated macrophages and tumor infiltrating lymphocytes contribute significantly to the development of immunosuppressive properties of tumor. In this study we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods Paraffin‑embedded tissue specimens from 48 esophageal squamous cell carcinoma patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1 and iNOS were used. For T-cells detection CD8, CD3, FOXP3 were used. As well we performed staining for PD-L1 that can be expressed on tumor associated macrophagesand tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log‑rank test. The correlation analysis was performed with Spearman correlation coefficient. Results The level of CD206 expression was associated with histological grade (p = 0.034), FOXP3 expression was associated with sex and age (p = 0.041, p = 0.003 respectively) and iNOS expression was associated with the disease stage (p = 0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR = 0.5407, p = 0.0462; HR = 0.4447, p = 0.0456 respectively). Significant association between PU.1 + and CD68 + macrophages (r = 0.752; P = 0.000) and between PU.1 + and CD163 + macrophages (r = 0.585; P = 0.000) was established, positive association between PU.1 and CD206 expression was also observed (r = 0.424; P = 0.001). Conclusions Large amounts of CD163 + macrophages and FOXP3+ Т-cells appear to be markers of good prognosis of esophageal squamous cell carcinoma. The number of PU.1 + macrophages strongly correlate with the number of CD68 + macrophages therefore usage of PU.1 as a potential macrophage marker can be recommended esophageal tumors.

scholarly journals CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3982
Author(s):  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Shau-Hsuan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Independent Prognostic Factor ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Patient Responses

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.

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14511-e14511 ◽  
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.

Novel genomic prognostic factors for nonsurgical esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15589-e15589
Author(s):  
Honghai Dai ◽  
Yang Shao ◽  
Xiaoling Tong ◽  
Xue Wu ◽  
Jiaohui Pang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Free Survival ◽  
Male Patients ◽  
The Impact

e15589 Background: Definitive concurrent chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients demonstrated great variations in responses and post-treatment progression inevitably. Methods: To identify prognostic factors that could assist in clinical judgment and make predictions ahead of disease relapse, we performed a targeted next generation sequencing of 416 cancer-related genes on primary tumor biopsies from 47 ESCC patients with locally advanced or metastatic nonsurgical diseases. Patients were subjected to dCRT treatment and local recurrence free survival (LRFS), progression free survival (PFS) and overall survival (OS) times were analyzed. Results: TP53 (78%), NOTCH1 (32%), ARID1A (13%), FAT1 (13%) and CDKN2A (13%) are the most commonly mutated genes in ESCC, while copy number gains are frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%) and YAP1 (11%). Multivariate analysis including clinical variables (age, gender and disease stage) and individual genetic alterations suggested that gender is an independent prognostic factor and male tend to have longer LRFS, PFS and OS after dCRT treatment. In addition, YAP1 amplification likely increased the risk of disease progression and death. To remove the impact of gender on prognosis, gender stratified survival analysis was performed and found that male patients with YAP1 amplification had significantly shorter LRFS (p = 0.002) and OS (p = 0.03), and also demonstrated a certain trend toward a shorter PFS (p = 0.06) than male patients without YAP1 amplification. Conclusions: YAP1 amplification might be a potentially useful biomarker in predicting treatment outcomes and selecting patients with high relapse risk for closely monitoring.

DJ-1 Could Predict Worse Prognosis in Esophageal Squamous Cell Carcinoma

2008 ◽  
Vol 17 (12) ◽  
pp. 3593-3602 ◽  
Author(s):  
H.-F. Yuen ◽  
Y.-P. Chan ◽  
S. Law ◽  
G. Srivastava ◽  
M. El-tanani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Worse Prognosis

PS02.200: A COMPREHENSIVE SCREENING OF THE FRA-1 REGULATORY GENES IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 179-179
Author(s):  
Takeshi Toyozumi ◽  
Isamu Hoshino ◽  
Haruhito Sakata ◽  
Kentaro Murakami ◽  
Masayuki Kano ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Cell Lines ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Primary Tumors ◽  
Expression Levels ◽  
Hmga1 Expression

Abstract Background The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration and invasion. We previously reported that a high Fra-1 expression level is associated with lymph node metastasis and a poor prognosis in patients with esophageal squamous cell carcinoma (ESCC). In this study, we identified the genes regulated by Fra-1 in ESCC. Methods We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray experiment and Biobase Upstream Analysis (Cytoline Solutions, Tokyo, Japan), and candidate genes regulated by Fra-1 in the ESCC cell lines were detected. The actual connection of Fra-1 to the promoter region was identified in a ChIP-PCR experiment. The expression levels of the candidate genes regulated by Fra-1 in the primary tumors of surgical specimens obtained from ESCC patients (n = 135) were compared to those observed in normal tissues using real-time PCR and immunohistochemical staining, and the clinicopathological features were analyzed. Results The results of the Biobase Upstream Analysis and ChIP-PCR showed high mobility group protein 1 (HMGA1) and hyaluronan mediated motility receptor (HMMR) to be significant genes regulated by Fra-1. The expression levels of both HMGA1 and HMMR were found to closely correlate with the Fra-1 expression in the clinical specimens. The patients with a positive HMGA1 expression had a poorer prognosis than those with a negative expression (P = 0.017) and the patients with positive HMMR expression also had a poorer prognosis (P = 0.018). Moreover, a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor in the ESCC patients. Conclusion HMGA1 and HMMR are regulated by Fra-1 in the setting of ESCC and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulating the HMGA1 and HMMR expression may become a practical treatment strategy against ESCC in the future. Disclosure All authors have declared no conflicts of interest.

scholarly journals Significance of Circular FAT1 as a Prognostic Factor and Tumor Suppressor for Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Wataru Takaki ◽  
Hirotaka Konishi ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
Satoshi Kataoka ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Cancer Specific Survival ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Migration And Invasion

Abstract Background Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC). Method CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed. Results CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels. Conclusion The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.

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