Transcription/Expression of KLRB1 Gene as A Prognostic Indicator in Human Esophageal Squamous Cell Carcinoma

2020 ◽  
Vol 23 (7) ◽  
pp. 667-674
Author(s):  
Guangwei Zhang ◽  
Ying Liu ◽  
Fajin Dong ◽  
Xianming Liu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Prediction Model ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Risk Groups ◽  
Prognostic Indicator ◽  
Dismal Prognosis ◽  
N Stage

Aim and Objective: Esophageal squamous cell carcinoma (ESCC) is the most prevalent type of cancer with worldwide distribution and dismal prognosis despite ongoing efforts to improve treatment options. Therefore, it is essential to determine the prognostic factors for ESCC. Methods and Results: We determined KLRB1 to be a prognostic indicator of human ESCC. KLRB1 was expressed at low levels in ESCC patients. Based on the risk score, patients were divided into high and low-risk groups. High-risk patients showed a poor survival rate. The prediction model based on the N stage, sex, and KLRB1 was significantly better than that based on the N stage and sex. The modified prediction model showed a robust ROC curve with an AUC value of 0.973. The knockdown of KLRB1 inhibited the growth of human ESCC cells. KLRB1 regulated Akt, mTOR, p27, p38, NF-κB, Cyclin D1, and JNK signaling, which was consistent with the result of GSEA. Conclusion: KLRB1 is a potential prognostic marker for human ESCC patients.

scholarly journals Chemotherapy alone versus definitive concurrent chemoradiotherapy for cT4b esophageal squamous cell carcinoma: a population-based study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chia-Chin Li ◽  
Chih-Yi Chen ◽  
Ying-Hsiang Chou ◽  
Chih-Jen Huang ◽  
Hsiu-Ying Ku ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Statistical Significance ◽  
Treatment Options ◽  
Population Based ◽  
Primary Analysis

Abstract Background The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. Methods Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. Results Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24–0.53, P < 0.001). Similar results were found for IECM. Statistical significance was only observed in the standard RT dose but not in the low dose in subgroup analyses. Conclusions In this population-based nonrandomized study of cT4bNanyM0 ESqCC patients from Asia (Taiwan), we found that the use of radiotherapy with chemotherapy was associated with better overall survival than chemotherapy alone. Further studies (especially RCTs) are needed to confirm our findings.

scholarly journals A predictive model for treatment response in patients with locally advanced esophageal squamous cell carcinoma after concurrent chemoradiotherapy: based on SUVmean and NLR

2020 ◽  
Author(s):  
chunsheng wang ◽  
Kewei Zhao ◽  
Shanliang Hu ◽  
Yong Huang ◽  
Li Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Prediction Model ◽  
Cell Carcinoma ◽  
Treatment Outcomes ◽  
Predictive Model ◽  
Treatment Response ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Training Set

Abstract Background: We conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT). Methods: We retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n=83) and in all sets. Results: A high SUVmean (>5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p<0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9% and 92.1% in the training set, 95.8% and 97.1% in the testing set, and 92.2% and 91.8% in all sets, respectively). Conclusions: The pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.

scholarly journals Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression

2015 ◽  
Vol 36 (1) ◽  
pp. 100-110 ◽  
Author(s):  
Kai Liu ◽  
Liyi Li ◽  
Aizemaiti Rusidanmu ◽  
Yongqing Wang ◽  
Xiayi Lv
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Pearson Correlation ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Dismal Prognosis

Aims: Changes in the expression of microRNAs (miRNAs) have been found in many cancers. This study aimed to investigate the expression of miR-1294 in patients with esophageal squamous cell carcinoma (ESCC) and its effect on prognosis. The underlying mechanism was explored as well. Methods: We examined the expression of miRNA in human ESCC cancer tissues and adjacent non-tumor controls using quantitative reverse transcription polymerase chain reaction (qRT-PCR). And the relationship between expressions of miR-1294 and ESCC prognosis was analyzed in this study. Over-expression and knock-down methods were used to investigate the biological functions of miRNA-1294. The effect of miRNA-1294 on cell proliferation was evaluated by MTT. Besides, the function of miR-1294 on cell migration and invasion were evaluated by transwell assays. Results: MiR-1294 was significantly down-regulated in human ESCC tissues compared with the non-tumor controls tissues (P=0.014). And patients with low miR-1294 expression had a significantly poorer prognosis than those with a high miR-1294 expression (P=0.040). Negative association was defined between the expression of miR-1294 and the c-MYC expression in ESCC patients (Pearson correlation, r=-0.299, P=0.0079). Additionally, it was found that miR-1294 suppress esophageal cancer cells proliferation, migration and invasion capacity through targeting c-MYC in vitro. Conclusions: Down-regulation of miR-1294 correlates with poor prognosis of ESCC. It's partially due to the reduced function of c-MYC. This study may give insight into the understanding of pathogenesis of esophageal cancer and provide evidence for diagnosis and treatment of esophageal cancer.

Sintilimab in patients with advanced esophageal squamous cell carcinoma refractory to previous chemotherapy: A randomized, open-label phase II trial (ORIENT-2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4511-4511 ◽  
Author(s):  
Jianming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Zhijun Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Phase 2 Trial ◽  
Line Chemotherapy

4511 Background: Patients (pts) with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line chemotherapy have limited treatment options. The study aims to evaluate the efficacy and safety of sintilimab, a PD-1 inhibitor, versus chemotherapy in these pts, and explore predictive value of PD-L1 and neutrophil-to-lymphocyte ratio (NLR) on efficacy of sintilimab. Methods: The open-label, multi-center phase 2 trial (NCT03116152) enrolled advanced ESCC pts refractory to first-line chemotherapy, and randomly assigned (1:1) them to receive sintilimab (200mg, Q3W) or chemotherapy (paclitaxel, 175mg/m2, Q3W; or irinotecan, 180mg/m2, Q2W), intravenously. The primary endpoint was overall survival (OS). Explorative endpoint were effects of PD-L1 and NLR on efficacy of sintilimab. Results: From May 16, 2017 to Aug 30, 2018, 190 pts were randomly assigned to sintilimab or chemotherapy (n = 95 per group). With the median follow-up of 7.2 months for sintilimab group and 6.2 months for chemotherapy group, the median OS in sintilimab was significantly higher than chemotherapy (7.2m vs. 6.2m, hazard ratio [HR] 0.70, P = 0.034). The objective response rate (ORR) was greater in sintilimab than chemotherapy with 12.6% vs. 6.3%, and the median duration of response was longer (8.3m vs. 6.2m). Incidences of treatment-related adverse events (TRAEs) of any grade (54.3% vs. 90.8%) and of grade 3-5 (20.2% vs. 39.1%) were both numerically less in sintilimab than in chemotherapy. The ORR in sintilimab versus chemotherapy in pts with tumor PD-L1 tumor proportion score (TPS) ≥1% and with TPS ≥10% were 20.2% vs. 0%, and 35.7% vs. 0%, respectively. In sintilimab group, pts with low NLR ( < 3) had a significant longer median OS (HR 0.54, P = 0.019) than with high NLR. Conclusions: Sintilimab was superior to chemotherapy with a significantly prolonged survival benefit and a favorable safety profile in pts with advanced ESCC refractory to first-line chemotherapy. High tumor PD-L1 expression (TPS ≥1% or ≥10%) might indicate more response benefit to sintilimab for these pts, and low NLR might be a positive predictive factor for sintilimab. Clinical trial information: NCT03116152 .

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