scholarly journals Perineural invasion correlates with postoperative distant metastasis and poor overall survival in patients with PT1–3N0M0 esophageal squamous cell carcinoma

2015 ◽  
pp. 3153 ◽  
Author(s):  
Xianghui Du ◽  
liming sheng ◽  
Yongling Ji

2021 ◽  
Vol 9 (10) ◽  
pp. e002836
Author(s):  
Peipei Wang ◽  
Yueyun Chen ◽  
Qingqin Long ◽  
Qing Li ◽  
Jiangfang Tian ◽  
...  

BackgroundImmune checkpoint (IC) blockades (ICBs) significantly improve patients’ clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy.MethodsRNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center.ResultsThe results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence.ConclusionHigh expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.



2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15587-e15587
Author(s):  
Yuan Li ◽  
Jiagen Li ◽  
Nan Sun ◽  
Mei Luo ◽  
Chengcheng Zhou ◽  
...  

e15587 Background: Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Methods: In this study, we identified a NSUN2 methylated lncRNA (NMR), which is significantly upregulated in esophageal squamous cell carcinoma (ESCC), functions as a key regulator of ESCC tumor metastasis and drug resistance. Results: In microarray data of 119 paired ESCC and normal tissues, NMR was significantly overexpressed in ESCC (P < 0.001), and overexpression of NMR indicated poor overall survival of ESCC patients (P = 0.003); in RNA sequencing data of 20 cancer types from TCGA, including 426 head and neck squamous cell carcinoma (HNSC) patients, NMR was significantly upregulated in HNSC tissues (P < 0.01), and patients with higher T stage, N stage, and m stage had significantly higher NMR expression (P < 0.05). Dysregulation of NMR was also validated in an independent cohort with 83 ESCC patients. Consistently, NMR was significantly overexpressed in ESCC (P < 0.001), and high NMR expression was significantly associated with lymph node metastasis and poor overall survival (P < 0.05). Functional experiments demonstrated that NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. RNA sequencing after interference highlighted alterations in collagen metabolic process and ERK1 and ERK2 cascade. Further validation proved that NMR could promote the expression of MMP3 and MMP10, at least partially by ERK1/2 pathway. Conclusions: Taken together, these findings suggest that NMR functions as an oncogenic gene in ESCC and may serve as novel biomarker and therapeutic target in ESCC.





2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.



PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e63581 ◽  
Author(s):  
Yang Wang ◽  
Shijie Sheng ◽  
Jianzhi Zhang ◽  
Sijana Dzinic ◽  
Shaolei Li ◽  
...  


2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.



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