scholarly journals Circulating exosome-derived miR-191-5p is a novel therapeutic biomarker for radiotherapy in esophageal squamous cell carcinoma patients

2020 ◽  
Author(s):  
HUAN WANG ◽  
Masayuki Kano ◽  
Yasunori Matsumoto ◽  
Takeshi Toyozumi ◽  
Satoshi Endo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Gene Set Enrichment Analysis ◽  
Free Survival ◽  
Patient Prognosis ◽  
Low Expression

Abstract Background: Exosomes are nano-sized extracellular vesicles and are detectable in most body fluids. Circulating exosomal microRNAs are an easily obtained, and they could be minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. Radiotherapy is one of the most important treatment option for ESCC, and it would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance. Methods: A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma before radiotherapy. miR-191-5p was selected because it was found to be associated with the prognosis in ESCC based on the findings of previous reports. As a result, we decided to perform more studies to elucidate the significance of miR-191-5p. Gain-of-function analyses were performed to evaluate the functional significance of miR-191-5p in ESCC progression. The effects of miR-191-5p on ESCC radiosensitivity were determined by cell proliferation, a clonogenic survival assay and an apoptosis assay. A gene set enrichment analysis was used to investigate the downstream signaling pathway related to the miR-191-5p functions. The 5-year progression-free survival (PFS) rate was used to directly compare the usefulness of these biomarkers for determining the patient prognosis between the miR-191-5p high expression patients and low expression patients. Results: A subset of seven microRNAs (miR-628, miR-363, miR-191-5p, miR-185, miR-148a, miR-320d, miR-30e) was identified to be candidates of therapeutic biomarker for ESCC patients underwent radiotherapy in a global microRNA expression analysis. A high miR-191-5p expression promoted ESCC cell proliferation, invasion and migration and induced G0/G1 to S/G2M transition. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may directly target death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression. Conclusion: Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.

scholarly journals A Radiomics Nomogram for Non-Invasive Prediction of Progression-Free Survival in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Ting Yan ◽  
lili liu ◽  
Meilan Peng ◽  
Zhenpeng Yan ◽  
Qingyu Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Validation Cohort ◽  
Progression Free Survival ◽  
Tnm Staging ◽  
Free Survival ◽  
Training Cohort ◽  
Radiomics Signature

Abstract Objectives: To construct a prognostic model for preoperative prediction based on computed tomography (CT) images of esophageal squamous cell carcinoma (ESCC). Methods: Radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) with high throughput radiomics features that extracted from the CT images of 272 patients (204 in training and 68 in validation cohort), who were pathologically confirmed ESCC. Multivariable logistic regression was adopted to build the radiomics signature and another predictive nomogram model, which was composed with radiomics signature, traditional TNM stage and clinical features. Then its performance was assessed by the calibration and decision curve analysis (DCA). Results: 16 radiomics features were selected from 954 to build a radiomics signature，which were significantly associated with progression-free survival (PFS) (p<0.001). The area under the curve (AUC) of performance was 0.891 (95% CI: 0.845-0.936) for training cohort and 0.706 (95% CI: 0.583-0.829) for validation cohort. The radscore of signatures’ combination showed significant discrimination for survival status in both two cohort. Kaplan-Meier survival curve further confirmed the radscore has a better prognostic performance in training cohort. Radiomics nomogram combined radscore with TNM staging showed significant improvement over TNM staging alone in training cohort (C-index, 0.802 vs 0.628; p<0.05), and it is the same with clinical data (C-index, 0.798 vs 0.660; p<0.05). Findings were confirmed in the validation cohort. DCA showed CT-based radiomics model will receive benefit when the threshold probability was between 0 and 0.9. Heat maps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric CT-based radiomics nomograms provided improved prognostic ability in ESCC.

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.

scholarly journals Expression of HDAC8 indicates poor prognosis of esophageal squamous cell carcinoma and progression to advanced stage

2019 ◽  
Vol 6 (1) ◽  
pp. 19-25
Author(s):  
Cheng Yufeng ◽  
Effat Un Nesa ◽  
Xuan Chen ◽  
Cong Wang ◽  
Xue Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Lymph Node Status ◽  
Nuclear Staining ◽  
Operating Characteristics ◽  
Free Survival

Background: We determined to assess the HDAC8 expression in esophageal squamous cell carcinoma (ESCC) patients and prognostic potential though there is only a little research contribution regarding HDAC8 to tumorigenesis of ESCC. Methods: The immunohistochemical expression of HDAC8 was investigated on tissue microarrays (TMAs) from 110 patients with esophageal squamous cell carcinoma.The nuclear staining intensity is calculated by the immune reactivity score ranging from (0-12) and divides them into two groups: no expression group and overexpression. Results: The median follow-up duration was 70 months. Highly regulated HDAC8 protein significantly predicted decreased 5-year overall survival (p = 0.001) and progression-free survival (p = 0.001) demonstrated by the log-rank test. Furthermore, HDAC8 protein acts as an independent prognostic factor for overall survival and progression-free survival, which determined after multivariate analyses. By Receiver operating characteristics (ROC) analysis, the value of HDAC8 was (0.63±0.54,p=0.04) according to advance cancer stage and (0.59±0.06,p=0.04) according to the lymph node status found in the Area under the curve (AUC). Conclusion: HDAC8 protein is highly regulated in ESCC tissues and potential prognostic indicator for diagnosing patients with decreased survival period.

A prospective, nonrandomized phase II/III trial of definitive chemoradiation, with or without cetuximab, in advanced esophageal squamous cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14645-e14645
Author(s):  
Yongshun Chen ◽  
Jianhua Wang ◽  
Xiaoyuan Wu ◽  
Chunyu He ◽  
Wen Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Free Survival ◽  
Group A ◽  
Group B

e14645 Background: Chemoradiotherapy is the standard treatment option for patients with esophageal cancer unsuitable for surgery, but the majority of patients will die of their disease, most commonly with local tumor progression/recurrence. We initiated this study to determine the efficacy and safety of the addition of cetuximab with paclitaxel, cisplatin, and radiation for patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 127 patients with clinical stage II–IVa disease were selected to receive combined-modality therapy consisting of cetuximab (400 mg/m2/wk week 1, then 250 mg/m2/wk week 2-8), paclitaxel (45 mg/m2/wk) and cisplatin (20 mg/m2/wk) in weeks 2-8 with 59.4 Gy of radiation (Group A, n = 29) versus the same chemoradiotherapy schedule but without cetuximab (Group B, n = 98). Results: At the time of this analysis, 27 and 88 patients were available for evaluation of response and survival in Group A and B respectively. In Group A, 20 patients (74.1%) achieved complete response (CR) and 7 (25.9%) achieved partial response (PR), resulting in an objective response rate (ORR) of 100%. The 1- and 2-year progression-free survival (PFS) was 91.2% and 85.1%, the median PFS was not reached. No association between tumor EGFR expression and response or survival was found. In Group B, 33 patients (37.5%) achieved CR, 51 (58.0%) achieved PR and 4 (4.5%) had stable disease, thus the ORR was 95.5%. The 1- and 2-year PFS was 89.0% and 50.5%, with the median PFS of 24.3 months. The difference in PFS between the two groups was statistically significant (p = 0.011). Treatment-related toxicities were generally grade 1 or 2. The most common toxicities were rash (89.3%), followed by neutropenia (71.4%) and esophagitis (60.7%) in chemoradiation-plus-cetuximab group. Adverse events were most often neutropenia (81.8%) and esophagitis (76.1%) in chemoradiation group. Locoregional failure rate was 3.7% and 15.9% in Group A and B, respectively. Conclusions: Cetuximab can be safely administered with chemoradiation and may prolong progression-free survival for Chinese patients with ESCC.

Efficacy and Safety Assessment of Paclitaxel in Patients with Docetaxel-Resistant Esophageal Squamous Cell Carcinoma

Chemotherapy ◽  
2016 ◽  
Vol 61 (5) ◽  
pp. 262-268 ◽  
Author(s):  
Hiroo Imai ◽  
Keigo Komine ◽  
Shin Takahashi ◽  
Ken Saijo ◽  
Yoshinari Okada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Cross Resistance ◽  
Survival Times ◽  
Free Survival ◽  
Development Of Resistance ◽  
Suitable Treatment

Background: Incomplete cross-resistances between paclitaxel (PTX) and docetaxel (DTX) has been demonstrated in several types of cancer. The objective of the present study was to assess the existence of cross-resistance between PTX and DTX in esophageal squamous cell carcinoma. Methods: Patients in the PTX group received PTX without DTX pretreatment, patients in the prior DTX (Pr-DTX) group received PTX after the development of resistance to DTX, and patients in the DTX group received DTX without subsequent PTX treatment. Results: A total of 73 patients were enrolled. The response rates to PTX in the PTX and Pr-DTX groups were 22.7 and 20.0%, respectively. The median progression-free survival times from the first day of PTX treatment in the PTX and Pr-DTX groups were 113 (95% CI 56-154) and 97 days (95% CI 36-189), respectively. The median overall survival times from the first day of DTX treatment in the Pr-DTX and DTX groups were 315 (95% CI 124-453) and 148 days (95% CI 139-177), respectively. Conclusions: There is no or incomplete clinical cross-resistance between PTX and DTX in esophageal squamous cell carcinoma. Replacement of DTX with PTX is a suitable treatment option for patients with DTX-resistant esophageal squamous cell carcinoma.

The Clinical Prognostic Value of LRG1 in Esophageal Squamous Cell Carcinoma

2019 ◽  
Vol 19 (9) ◽  
pp. 756-763 ◽  
Author(s):  
Yuanyuan Wang ◽  
Qian Xing ◽  
Xue Chen ◽  
Jianbo Wang ◽  
Shanghui Guan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Prognostic Prediction ◽  
Invasion Assays

Background:Leucine-rich-alpha-2-glycoprotein1 (LRG1) is a new oncogene-related gene, which has been proven important for the development and poor prognosis of human cancers. However, whether it participates in esophageal squamous cell carcinoma (ESCC) progression remains unclear.Objective:To investigate the expression level and functional influence of LRG1 in ESCC.Methods:The expression of LRG1 was evaluated on the mRNA and protein level in ESCC patients. Then, correlation of LRG1 expression with clinicpathological variables was analyzed in ESCC. Besides, to clarify the biological function of LRG1, Eca109 and KYSE150 cells were transfected with LRG1 shRNA, the cell viability, clonal efficiency, apoptosis and invasion assays in vitro were performed.Results:LRG1 was significantly over-expressed in ESCC and related to deeper invasion depth (T stage) and distal metastasis (M stage). Kaplan-Meier analysis indicated that LRG1 up-regulation in ESCC was closely correlated to worse clinical survival (overall survival and progression-free survival), all P<0.001. LRG1 was confirmed to be an independent poor premonitory indicator for clinical outcomes in ESCC through the univariate and multivariate analyses. Down-regulation of LRG1 in ESCC cells markedly suppressed cell proliferation and invasion, stimulated apoptosis (all p <0.01).Conclusion:LRG1 might play a significant role in the progression of ESCC, and could be served as a promising prognostic prediction for ESCC patients.

scholarly journals A Radiomics Nomogram for Non-Invasive Prediction of Progression-Free Survival in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Ting Yan ◽  
Lili Liu ◽  
Meilan Peng ◽  
Zhenpeng Yan ◽  
Qingyu Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Validation Cohort ◽  
Progression Free Survival ◽  
Tnm Staging ◽  
Free Survival ◽  
Training Cohort ◽  
Radiomics Signature

Abstract To construct a prognostic model for preoperative prediction on computed tomography (CT) images of esophageal squamous cell carcinoma (ESCC), we constructed radiomics signature with high throughput radiomics features extracted from CT images of 272 patients (204 in training and 68 in validation cohort). Multivariable logistic regression was adopted to build the radiomics signature and another predictive nomogram model, which was composed with radiomics signature, traditional TNM stage and clinical features. 16 radiomics features were selected from 954 to build a radiomics signature，which were significantly associated with progression-free survival (PFS) (p<0.001). The area under the curve (AUC) of performance was 0.891 (95% CI: 0.845-0.936) for training cohort and 0.706 (95% CI: 0.583-0.829) for validation cohort. The radscore of signatures’ combination showed significant discrimination for survival status. Radiomics nomogram combined radscore with TNM staging showed significant improvement over TNM staging alone in training cohort (C-index, 0.802 vs 0.628; p<0.05), and it is the same with clinical data (C-index, 0.798 vs 0.660; p<0.05), which were confirmed in validation cohort. DCA showed the model will receive benefit when the threshold probability was between 0 and 0.9. Collectively, multiparametric CT-based radiomics nomograms provided improved prognostic ability in ESCC.

scholarly journals Nomogram based on SIS predicting the survival of non-surgical thoracic esophageal squamous cell carcinoma treated by IMRT

2021 ◽  
Author(s):  
Xingyu Du ◽  
Shuchai Zhu ◽  
Jing Dong ◽  
Ke Yan ◽  
Xiaobin Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Inflammatory Markers ◽  
Progression Free Survival ◽  
Data Set ◽  
Free Survival

Abstract Background: Several inflammatory markers have been reported to be associated with clinical outcomes in patients with esophageal squamous cell carcinoma (ESCC). This study was to evaluate several pre-radiotherapy serum inflammatory indicators, including the neutrophil / lymphocytes ratio (NLR), platelet / lymphocyte (PLR), systemic immune-inflammatory index (SII), systemic inflammation score(SIS), and compare which one has the highest predicted survival value. Finally, combining inflammatory markers with traditional prognostic factors, a new Nomogram model was developed to predict overall survival (OS) and progression-free survival (PFS) for ESCC patients receiving radiotherapy (RT) or chemoradiotherapy (CRT). Methods: This study retrospectively reviewed the data of 245 patients with thoracic esophageal squamous cell carcinoma (ESCC) underwent RT or CRT in the Fourth Hospital of Hebei Medical University from January 2013 to December 2015. The survival differences of these indexes were compared by the Kaplan-Meier method, and the univariate and the multivariate analyses were performed to determine these prognostic factors of overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional hazards regression models were used to create nomogram for OS and PFS.Results: 239 patients met the eligibility criteria. The estimated 1-, 3-, and 5-year OS and PFS rates were 74.6%, 36.8%, 26.5% and 58.4%, 31.3%, 20.5%, respectively, for the whole group. The difference in survival between OS and PFS was significant when univariate analysis were applied based on these inflammation-based measures. Multivariate analysis showed that tumor length, T stage, TNM stage, chemotherapy, SIS were predictive variables for OS and PFS in the multivariate model. The nomogram model established based on multivariate models of training data set had good predictive ability, the unadjusted C-index was 0.701 (95% CI, 0.662– 0.740) and 0.695 (95% CI, 0.656 - 0.734) for OS and PFS. Conclusions: This study show that SIS, as a comprehensive indicator of inflammation and nutrition, had the strongest predictive power for evaluating prognosis. Moreover, our nomogram can accurately predict OS and PFS after treatment and may provide guidance regarding adjuvant therapy and surveillance.

scholarly journals Definitive chemoradiotherapy has comparable survival outcomes to esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: real world data

2021 ◽  
Author(s):  
Kentaro Sawada ◽  
Hiroki Yukami ◽  
Saori Mishima ◽  
Hisashi Fujiwara ◽  
Tomohiro Kadota ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Real World ◽  
Progression Free Survival ◽  
Real World Data ◽  
Free Survival

Abstract Background Recently, the JCOG0502 has shown a comparable efficacy of chemoradiotherapy and esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma. However, few studies have compared the clinical outcomes of these treatments in esophageal squamous cell carcinoma patients (including elderly patients) based on real-world data. Methods This retrospective study determined real-world outcomes in patients who underwent chemoradiotherapy or esophagectomy, including those with clinical T1N0M0 esophageal squamous cell carcinoma, between 2009 and 2017 at the National Cancer Center Hospital East. Results Among a total of 156 patients, 120 and 36 patients underwent esophagectomy and chemoradiotherapy, respectively; 138, 12 and 6 patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively; and 33 and 123 patients had clinical tumor depth MM-SM1 and SM2-SM3, respectively. In a median follow-up of 72 months, 5-year progression-free survival and overall survival were respectively 77.0% and 81.5% in the esophagectomy group and 74.4% and 82.6% in the chemoradiotherapy group (P = 0.48 and, P = 0.89). Moreover, no treatment-related death was detected in both groups. In elderly patients (75 years or older), 5-year progression-free survival and overall survival were not significantly different between esophagectomy and chemoradiotherapy groups (5-year progression-free survival: 72.3% vs. 81.8%, P = 0.38; 5-year overall survival: 76.9% vs. 81.8%, P = 0.59). Conclusions This real-world study confirms the results of a previous clinical trial, and the present findings support chemoradiotherapy as one of the standard treatment options in patients of all ages with clinical T1N0M0 esophageal squamous cell carcinoma.

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