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Retrospective analysis of predictive factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

ABSTRACT: This study aimed to identify the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma and use these factors to establish a prediction model. We retrospectively analyzed the data from training set (n = 280) and validation set (n = 240) underwent radical esophagectomy between March 2005 and April 2018. Our results of univariate and multivariate analyses showed that tumor size, tumor invasion depth, tumor differentiation and lymphovascular invasion were significantly correlated with LNM. Incorporating these 4 variables above, model A achieved AUC of 0.765 and 0.770 in predicting LNM in the training and validation sets, respectively. Adding macroscopic type to the model A did not appreciably change the AUC but led to statistically significant improvements in both the integrated discrimination improvement and net reclassification improvement. Finally, a nomogram was constructed by using these five variables and showed good concordance indexes of 0.765 and 0.770 in the training and validation sets, and the calibration curves had good fitting degree. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. It is possible to predict the status of LNM using this nomogram score system, which can aid the selection of an appropriate treatment plan.

SUBMITTER: Ruan R

PROVIDER: S-EPMC8368005 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Clinical nomogram for lymph node metastasis in pathological T1 esophageal squamous cell carcinoma: a multicenter retrospective study.

Project description:Background:Endoscopic resection is increasingly used to treat pathological T1 (pT1) esophageal cancer (EC) patients. However, the procedures are limited by lymph node metastasis (LNM) and remain controversial. We aimed to construct a nomogram to predict the risk of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). Methods:A total of 243 patients with pT1 ESCC who underwent esophagectomy and lymph node dissection at two different institutes between February 2013 and June 2019 were analyzed retrospectively. Patients were categorized into the negative group and the positive group according to whether there was LNM. Risk factors for LNM were evaluated by univariate and multivariate analyses. The nomogram was used to estimate the individual risk of LNM. Results:Forty-six (18.9%) of the 243 patients with pT1 ESCC exhibited LNM. The LNM rate in patients with stage T1a disease was 5.7% (5/88), and the rate in patients with stage T1b disease was 26.5% (41/155). Multivariable logistic regression analysis showed that tumor differentiation [odds ratio (OR) =1.942, 95% confidence interval (CI): 1.067-3.536, P=0.030], the T1 sub-stage (OR =4.750, 95% CI: 1.658-13.611, P=0.004), the preoperative alanine aminotransferase/aspartate aminotransferase ratio (LSR) (OR =5.371, 95% CI: 1.676-17.210, P=0.005), and the high-density lipoprotein cholesterol (HDL-C) level (OR =5.894, 95% CI: 1.917-18.124, P=0.002) were independent risk factors for LNM. The nomogram had relatively high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.803 (95% CI: 0.732-0.873). The calibration curve showed that the predicted probability of LNM was in good agreement with the actual probability. Conclusions:Clinicopathological and hematological parameters of tumor differentiation, the T1 sub-stage, the preoperative LSR, and the HDL-C level may predict the risk of LNM in T1 ESCC. The risk of LNM can be predicted by the nomogram.

| S-EPMC7186726 | biostudies-literature

A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma.

Project description:Treatment modalities in esophageal squamous cell carcinoma (ESCC) depend largely on lymph node metastasis (LNM) status. With suboptimal detection sensitivity of existing imaging techniques, we propose a methylation signature which identifies patients with LNM with greater accuracy. This would allow precise stratification of high-risk patients requiring more aggressive treatment from low-risk ESCC patients who can forego radical surgery. An unbiased genome-wide methylation signature for LNM detection was established from an initial in silico discovery phase. The signature was tested in independent clinical cohorts comprising of 249 ESCC patients. The prognostic potential of the methylation signature was compared to clinical variables including LNM status. A 10-probe LNM associated signature (LNAS) was developed using stringent bioinformatics analyses. The area under the curve values for LNAS risk scores were 0.81 and 0.88 in the training and validation cohorts respectively, in association with lymphatic vessel invasion and tumor stage. High LNAS risk-score was also associated with worse overall survival [HR (95% CI) 3 (1.8-4.8), p < 0.0001 training and 3.9 (1.5-10.2), p = 0.001 validation cohort]. In conclusion, our novel methylation signature is a powerful biomarker that identifies LNM status robustly and is also associated with worse prognosis in ESCC patients.

| S-EPMC7331270 | biostudies-literature

Prognostic impact of thoracic duct lymph node metastasis in esophageal squamous cell carcinoma.

Project description:AimWe have previously reported the existence of lymph nodes surrounding the thoracic duct ( TDLN) and transthoracic esophagectomy (TTE) with thoracic duct (TD) resection increased the number of lymph nodes (LNs) retrieved. The current study aims to evaluate the prognostic impact of TDLN metastasis in esophageal cancer patients subdivided by its location and comparing the patients' survival with those with extra-regional LN metastasis.MethodsPatients who underwent TTE with TD resection for esophageal squamous cell carcinoma (ESCC) were reviewed. Patients were classified into those with or without TDLN metastasis, and clinicopathological factors were compared between groups. TDLN was further divided into TDLN-Ut/Mt/Lt based on the location in the mediastinum. The relapse-free survival (RFS) and overall survival (OS) were compared between groups.ResultsOf 232 patients, TDLN metastasis was observed in 17 (7%). RFS and OS were significantly worse in the TDLN metastasis group. TDLN metastasis was shown to be an independent prognostic factor for RFS and OS in the multivariate analysis. The negative prognostic impact of TDLN metastasis was evident in TDLN-Mt/Lt. The RFS and OS of patients with TDLN metastasis were almost identical to those with positive LN metastasis in extra-regional LNs.ConclusionTDLN metastasis was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be independently classified from the current regional LNs. Given that neoadjuvant therapy has been a standard, we might need to introduce adjuvant therapy when TDLN metastasis is observed.

| S-EPMC8164460 | biostudies-literature

Risk factors for lymph node metastasis of the left recurrent laryngeal nerve in patients with esophageal squamous cell carcinoma.

Project description:BackgroundThe factors for left recurrent laryngeal nerve (RLN) lymph node (LN) metastasis have important guiding significance for whether the left RLN LNs should be dissected in patients with esophageal squamous cell carcinoma (ESCC), but few studies are currently available. To analyze the risk factors of LN metastasis of the left RLN area and to assess which LNs should be dissected in ESCC.MethodsThis was a retrospective study of patients who underwent McKeown minimally invasive esophagectomy (MIE) (no neoadjuvant therapy) at Tianjin Medical University Cancer Institute and Hospital (from January 2016 to December 2019). The detection of left RLN LNs using enhanced computed tomography (CT) was compared with the pathological examination.ResultsOf the total 94 participants, 43 had LN metastasis. The metastatic LNs were mainly located next to left (18.1%) and right (14.9%) RLN, and the left gastric artery (13.8%). Tumor size, LN size, tumor invasion (T stage), N stage, and tumor node metastasis (TNM) stage were associated with left RLN LNs metastasis, while LN size was the only independently associated factor [odds ratio (OR) =1.569, 95% confidence interval (CI): 0.259-1.956, P=0.0012]. The area under receiver operating characteristic (ROC) curve (AUC) reached 0.877, with 64% sensitivity and 75% specificity using a cutoff of 5.5 mm LN size.ConclusionsThe size of left RLN LN is independently associated with metastasis. Left RLN LNs >5.5 mm at CT examination are more likely to be positive and should probably be dissected.

| S-EPMC8039656 | biostudies-literature

Is Routine Subcarinal Lymph Node Dissection Necessary in Superficial Esophageal Squamous Cell Carcinoma? A Propensity Score Matching Analysis.

Project description:Background: The purpose of this study was to investigate the impact of subcarinal lymph node dissection on short-term and long-term outcomes after esophagectomy in patients with superficial esophageal squamous cell carcinoma (ESCC). Methods: From January 2010 to December 2015, 490 patients with pT1 ESCC were enrolled in the study. Patients in subcarinal dissection or non-dissection group were matched randomly in a 2:1 ratio, eventually, 255 patients were selected for further statistical analysis. Results: The metastasis rate of subcarinal lymph nodes in superficial ESCC was 1.24% and significantly lower than the other stations (7.14-9.96%). Compared with dissection group, non- dissection group had shorter operation time (193±35 vs. 204±39, P=0.016), less blood loss (157±48 vs. 178±29, P=0.011) as well as lower incidence of pulmonary complications (9.4 vs. 20%, P=0.032). At a median follow-up of 46 months, the recurrent rate in each group was similar (16.5 vs. 15.3%, P=0.809). Survival analysis revealed no overall survival (P=0.992) and disease-free survival (P=0.665) reductions in non-dissection group. In univariate and multivariate analyses, subcarinal lymph node dissection was not a predictive factor of overall and disease-free survival in superficial ESCC. Conclusion: Subcarinal lymph node dissection was not beneficial and could be omitted in superficial ESCC.

| S-EPMC6584403 | biostudies-literature

Relationship of lymphovascular invasion with lymph node metastasis and prognosis in superficial esophageal carcinoma: systematic review and meta-analysis.

Project description:BACKGROUND:The development of tumor cells inside the lymphatics or blood vessels is known as lymphovascular invasion (LVI). The correlation between LVI, lymph node metastasis (LNM), and the diagnosis of superficial esophageal carcinoma (SEC) remains unclear. METHODS:We searched Embase, PubMed, Web of Science, and Cochrane Library databases for prospective articles to better understand the relationship between LVI, LNM, and SEC diagnosis. RESULTS:We included 23 articles containing data for 4749 patients (range: 54-598) in our meta-analysis. The hazard ratio between LVI and overall survival (OS) was 1.85 with 95% confidence interval (CI) (1.10-3.11, P?=?0.02). LNM rate was higher in SEC patients with LVI than SEC patients without LVI (univariate: OR?=?4.94, 95% CI: 3.74-6.53, P?<?0.0001; multivariate: OR?=?5.72, 95%CI: 4.38-7.4, P?<?0.0001). No obvious publication was found. CONCLUSIONS:The results indicate that LVI plays a dominant role in the prognosis of LNM in SEC and in the prognostic prediction for SEC.

| S-EPMC7057611 | biostudies-literature

Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma.

Project description:Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip. In this screening, we focused on differentially methylated regions (DMRs) that were associated with LNM of ESCC, as prime candidates for DNA methylation markers. We extracted three genes, HOXB2, SLC15A3, and SEPT9, as candidates predicting LNM of ESCC, using pyrosequencing and several statistical analyses in the discovery cohort. We confirmed that HOXB2 and SEPT9 were highly methylated in LNM-positive tumors in 59 ESCC validation samples. These results suggested that HOXB2 and SEPT9 may be useful epigenetic biomarkers for the prediction of the presence of LNM in ESCC.

| S-EPMC5514945 | biostudies-literature

Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma.

Project description:Human pituitary tumor-transforming 1 (PTTG1)/securin is a putative oncoprotein that is overexpressed in various tumor types. However, the involvement of PTTG1 in gastrointestinal cancer development and progression remains unclear. In this study, we investigated the clinical significance and biological effects of PTTG1 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical studies performed on 113 primary ESCC specimens revealed a high prevalence of PTTG1 overexpression (60.2%), which was significantly associated with lymph node metastasis (regional, P = 0.042; distant, P = 0.005), advanced tumor stage (P = 0.028), and poorer overall survival (P = 0.017, log-rank test; P = 0.044, Cox proportional hazard model). Eleven ESCC cell lines expressed PTTG1 protein at levels 2.4 to 6.6 times higher than those in normal esophageal epithelial cells (HEEpiC). PTTG1 protein expression was confined to the nucleus in HEEpiC cells but present in both the cytoplasm and nucleus in ESCC cells. Two small interfering RNAs (siRNA) inhibited PTTG1 mRNA and protein expression in three ESCC cell lines by 77% to 97%. In addition, PTTG1 down-regulation by these siRNAs significantly reduced cell motility in all three ESCC cell lines (P < 0.01) in vitro, as well as popliteal lymph node metastases of ESCC cells in nude mice (P = 0.020). Global gene expression profiling suggested that several members of the Ras and Rho gene families, including RRAS, RHOG, ARHGAP1, and ARHGADIA, represented potential downstream genes in the PTTG1 pathway. Taken together, these findings suggest that PTTG1 overexpression promotes cell motility and lymph node metastasis in ESCC patients, leading to poorer survival. Thus, PTTG1 constitutes a potential biomarker and therapeutic target in ESCCs with lymph node metastases.

| S-EPMC2988648 | biostudies-literature

Profiling circular RNA in esophageal squamous cell carcinoma (ESCC) with lymph node metastasis

Project description:Circular RNAs (circRNAs) have been identified as a novel class of non-conding RNAs, which are stable and have covalently single-stranded loop configuration.With the improvement of RNA-sequencing and bioimofrmatics, numerous dysregulated expression of circRNAs has been identified in kinds of physiological and pathological processes, especially in tumorigenesis. To date, however, the discovery of cirtical circRNA abnormalities, as well as their functions and underlying mechanisms, in the progress of esophageal squamous cell carcinoma (ESCC), is still unknown.

2021-08-31 | GSE150476 | GEO

Inter- and intratumor DNA methylation heterogeneity associated with lymph node metastasis and prognosis of esophageal squamous cell carcinoma.

Project description:Background: Esophageal squamous cell carcinoma (ESCC), one of the leading causes of cancer mortality worldwide, is a heterogeneous cancer with diverse clinical manifestations. However, little is known about the epigenetic heterogeneity and its clinical relevance for this prevalent cancer. Methods: We generated 7.56 Tb single-base resolution whole-genome bisulfite sequencing data for 84 ESCC and paired paraneoplastic tissues. The analysis identified inter- and intratumor DNA methylation (DNAm) heterogeneity, epigenome-wide DNAm alterations together with the functional regulators involved in the hyper- or hypomethylated regions, and their association with clinical features. We then validated the correlation between the methylation level of specific regions and clinical outcomes of 96 ESCC patients in an independent cohort. Results: ESCC manifested substantial inter- and intratumor DNAm heterogeneity. The high intratumor DNAm heterogeneity was associated with lymph node metastasis and worse overall survival. Interestingly, hypermethylated regions in ESCC were enriched in promoters of numerous transcription factors, and demethylated noncoding regions related to RXR transcription factor binding appeared to contribute to the development of ESCC. Furthermore, we identified numerous DNAm alterations associated with carcinogenesis and lymph node metastasis of ESCC. We also validated three novel prognostic markers for ESCC, including one each in the promoter of CLK1, the 3' untranslated region of ZEB2, and the intergenic locus surrounded by several lncRNAs. Conclusions: This study presents the first population-level resource for dissecting base-resolution DNAm variation in ESCC and provides novel insights into the ESCC pathogenesis and progression, which might facilitate diagnosis and prognosis for this prevalent malignancy.

| S-EPMC7053185 | biostudies-literature

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