Prognostic significance of middle paraesophageal lymph node metastasis in resectable esophageal squamous cell carcinoma

Huang, Hong; Hou, Jie; Liyu, Rao; Chen, Zerui; Borong, Shu; Liang, Hongwei

doi:10.1097/md.0000000000017531

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…Liu et al [ 13 ] and Ma et al [ 17 ] reported that patients with subcarinal LNM had a worse OS than those with paraesophageal and left gastric artery LNM. In contrast, Hong and colleagues [ 12 ] reported that the 5-year survival rate of patients with paraesophageal LNM was significantly lower than that of patients with LNM around the recurrent laryngeal nerve and subcarinal nerve. The aforementioned controversies may result from the differences in research purpose, inclusion criteria and sample size.…”

Section: Discussionmentioning

confidence: 98%

“…A previous study demonstrated that the paraesophageal, paracardial, and left gastric artery LNs presented higher metastatic rates than supraclavicular and paratracheal LNs [ 11 ]. Furthermore, ESCC patients with left gastric artery and middle paraesophageal LNM had poor overall survival (OS), revealing the potential differences in survival based on LNM site [ 12 , 13 ]. However, it is still unclear whether ESCC patients with LNM around the respiratory system and digestive system have favorable survival outcomes after curative esophagectomy.…”

Section: Introductionmentioning

confidence: 99%

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Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system

et al. 2023

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Background The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. Methods This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). Results In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41–1.77, P < 0.001). The nN staging definition: nN1 (1–2 positive pararespiratory/paradigestive LNs), nN2 (3–6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3–6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. Conclusions Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system

et al. 2023

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“…Esophageal cancer is often diagnosed at an advanced stage and the patient survival rate is very low due to the lack of specific symptoms and effective early diagnostic methods (21). Although multiple treatments, such as surgical resection, chemotherapy, and radiotherapy have been applied for EScc treatment, the prognosis of EScc remains poor (22)(23)(24). Therefore, it is of utmost importance to better understand the molecular mechanisms responsible for the development of EScc and to explore novel therapies with which to improve the survival of patients with EScc.…”

Section: Discussionmentioning

confidence: 99%

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway

Jian

Liu

et al. 2020

Int J Mol Med

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Esophageal squamous cell carcinoma (EScc) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group d (XPd) in the growth and invasion of EScc and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT-qPcR were used to detect the expression level of XPd in EScc tissue samples and adjacent normal esophageal tissue samples. The pEGFP-N2/XPd plasmid was transfected into human EScc cell lines (Ec9706 and Ec109). The proliferation, apoptosis, migration and invasion of Ec9706 or Ec109 cells were assessed following transfection with the XPd overexpression plasmid. The chemosensitivity of Ec9706 or Ec109 cells to cisplatin or fluorouracil was evaluated by CCK-8 assay. The expression levels of phosphoinositide 3-kinase (PI3K)/AKT, nuclear factor (NF)-κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling pathway-related genes were detected by RT-qPcR and western blot analysis. The results demonstrated that the expression level of XPd was markedly lower in EScc tissue samples than in adjacent normal esophageal tissue samples. The pEGFP-N2/XPd plasmid was successfully transfected into Ec9706 or Ec109 cells, inducing XPd overexpression. A High XPd expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of Ec9706 and Ec109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of Ec9706 and Ec109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p-AKT, c-Myc, Cyclin D1, Bcl-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPd inhibits the growth and invasion of Ec9706 and Ec109 cells, whilst also enhancing the chemosensitivity of Ec9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for EScc treatment and drug resistance.

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“…However, most patients are already in intermediate or advanced stages at the time of diagnosis, making surgical treatment less effective [ 5 – 7 ]. Despite the use of various therapeutic approaches, such as surgical resection, chemotherapy, and radiotherapy, the prognosis of ESCC patients remains poor [ 8 – 10 ]. Therefore, elucidating the underlying molecular mechanisms leading to the development of ESCC is crucial for the development of more innovative and effective therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

IL-1β promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway

Chen,

Yang,

Zheng

et al. 2024

Cell Death Discov.

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Esophageal cancer is a common type of cancer that poses a significant threat to human health. While the pro-inflammatory cytokine IL-1β has been known to contribute to the development of various types of tumors, its role in regulating esophageal cancer progression has not been extensively studied. Our studies found that the expression of IL-1β and FOXO3A was increased in esophageal squamous cell carcinoma (ESCC). IL-1β not only increased the proliferation, migration, and invasion of two ESCC cell lines but also promoted tumor growth and metastasis in nude mice. We also observed that IL-1β and FOXO3A regulated the process of epithelial-mesenchymal transition (EMT) and autophagy. The PI3K/AKT pathway was found to be involved in the changes of FOXO3A with the expression level of IL-1β. The AKT agonist (SC79) reversed the reduction of FOXO3A expression caused by the knockdown of IL-1β, indicating that IL-1β plays a role through the PI3K/AKT/FOXO3A pathway. Furthermore, the knockdown of FOXO3A inhibited ESCC development and attenuated the pro-cancer effect of overexpressed IL-1β. Targeting IL-1β and FOXO3A may be potentially valuable for the diagnosis and treatment of ESCC.

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Prognostic significance of middle paraesophageal lymph node metastasis in resectable esophageal squamous cell carcinoma

Cited by 6 publications

References 21 publications

Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system

Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway

IL-1β promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway

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