Dataset Information

High Serum Elafin Prediction of Poor Prognosis of Locoregional Esophageal Squamous Cell Carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor known to have locally advanced and metastatic features which cause a dismal prognosis. We sought to determine whether elafin, a non-invasive and secretory small-molecule marker, could be used to predict prognosis in locoregional ESCC patients in human and in vitro studies. In our human study, 119 subjects were identified as having incident and pathologically-proved ESCC with stage I-IIIA tumors from southern Taiwan between 2000 and 2016. We measured their serum elafin levels at baseline and followed them until the date of cancer death or until January 2020, the end of this study. Those with high serum elafin levels were found to have a 1.99-fold risk (95% confidence interval: 1.17-3.38) shorter survival than those who did not. In our in vitro experiments, elevated elafin levels were found to drive ESCC cell proliferation, migration and invasion, while attenuation of elafin level by shRNA abrogated those effects. We concluded that elafin promotes ESCC motility and invasion and leads to a worse clinical prognosis in ESCC patients without distant metastasis.

SUBMITTER: Wu IC

PROVIDER: S-EPMC8233752 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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High Serum Elafin Prediction of Poor Prognosis of Locoregional Esophageal Squamous Cell Carcinoma.

Wu I-Chen IC Wang Yao-Kuang YK Chen Yi-Hsun YH Wu Chun-Chieh CC Wu Meng-Chieh MC Chen Wei-Chung WC Wang Wen-Lun WL Lin Hung-Shun HS Chen Chou-Cheng CC Chou Shah-Hwa SH Liu Yu-Peng YP Wu Ming-Tsang MT

Cancers 20210621 12

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor known to have locally advanced and metastatic features which cause a dismal prognosis. We sought to determine whether elafin, a non-invasive and secretory small-molecule marker, could be used to predict prognosis in locoregional ESCC patients in human and in vitro studies. In our human study, 119 subjects were identified as having incident and pathologically-proved ESCC with stage I-IIIA tumors from southern Taiwan between 20 ...[more]

PMID: 34205756

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a severe disease with high mortality, and is associated with poor prognosis and frequent lymphatic metastasis. Therefore, prognostic indicators for ESCC are urgently needed. A-kinase anchor-protein 8-like (AKAP8L) is a member of the A kinase anchor-protein (AKAPs) family and is overexpressed in many cancers. However, the role of AKAP8L in ESCC remains unclear. The aim of this study is to investigate the expression patterns and prognostic value of AKAP8L in ESCC.MethodsThe mRNA expression of AKAP8L was analyzed from the dataset of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry was applied to detect the AKAP8L expression in tissue microarray. Pearson's chi-square test was carried out for the correlation analysis of clinicopathological features and AKAP8L expression. The prognostic significance of clinicopathological features and AKAP8L expression was determined by univariate and multivariate Cox hazard models. Kaplan-Meier survival curve was used for survival analysis.ResultsWe found that the mRNA level of AKAP8L was higher in tumor tissues than in adjacent tissues in TCGA and GEO dataset. High AKAP8L expression was associated with poor overall survival (OS) in ESCC patients (p = 0.0039). Besides, AKAP8L expression was highly expressed in patients with lymph node metastasis detected by ESCC tissue microarray (p = 0.0014). The comparison of the different clinicopathological features of ESCC between high and low AKAP8L expression groups revealed that high AKAP8L expression was related to lymph node stage (p = 0.041). Kaplan-Meier survival analysis revealed that high AKAP8L expression indicates an unfavorable progression-free survival (PFS) and OS in ESCC patients (p < 0.0001). Univariate and multivariate analyses confirmed that AKAP8L was an independent prognostic factor for PFS and OS in ESCC (p = 0.003 and p < 0.0001).ConclusionsIn conclusion, this study demonstrated that high expression of AKAP8L is associated with poor prognosis of ESCC and can be considered an independent risk factor for ESCC.

Project description:BackgroundThe identification of effective tumor markers is of paramount importance for the early diagnosis, treatment, and prognosis of esophageal squamous cell carcinoma (ESCC). The present study endeavors to identify efficacious serological markers that can differentiate patients with early-stage ESCC from those with benign esophageal lesions and healthy controls (HC). Cystatin-SN (CST1), an active cysteine protease inhibitor belonging to the Cystatin (CST) superfamily, is implicated in the pathogenesis of inflammation and tumorigenesis. The objective of this investigation is to assess the diagnostic, therapeutic, and prognostic potential of serum CST1 in ESCC.MethodsIn our prior RNA sequencing and screening endeavors, we have identified ten genes that are up-regulated in relation to esophageal cancer. Subsequently, we have verified the gene CST1 from the transcriptome data of the The Cancer Genome Atlas Program (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Following this, we conducted an enzyme-linked immunosorbent assay (ELISA) to ascertain the expression levels of CST1 in serum samples from clinical cohorts.ResultsThe study revealed a significant elevation in serum CST1 levels among patients with early-stage esophageal squamous cell carcinoma (ESCC) (7.41 ± 4.32 ng/ml) compared to those with esophageal benign lesions (4.67 ± 2.43 ng/ml) (p < 0.0001) and healthy controls (4.87 ± 2.77 ng/ml) (p < 0.0001). The diagnostic sensitivity of CST1 for ESCC was 75.68% (specificity 70.83%, AUC 0.775). Combination of CST1 and SCC-Ag exhibited the AUC up to 0.819. Additionally, serum CST1 levels exhibited a significant decrease at 1-2 weeks post-surgery (4.49 ± 3.31 ng/ml) compared to pre-surgery levels (7.68 ± 3.71 ng/ml) (p<0.0001). Survival analysis demonstrated a strong association between high (844/415-1543 d) or low (1490/645-1710 d) serum CST1 levels at diagnosis and overall survival time (p < 0.001). Furthermore, multivariate regression analysis confirmed CST1 (p=0.024, HR=2.023, 95%CI 1.099-3.725) as an independent prognostic factor.ConclusionSerum CST1 has the potential to function as a diagnostic indicator for distinguishing early-stage esophageal squamous cell carcinoma (ESCC) from individuals with benign esophageal lesions and healthy individuals. Additionally, it could serve as a prognostic predictor and therapeutic efficacy indicator for patients with ESCC.

Dataset Information

High Serum Elafin Prediction of Poor Prognosis of Locoregional Esophageal Squamous Cell Carcinoma.

Publications

High Serum Elafin Prediction of Poor Prognosis of Locoregional Esophageal Squamous Cell Carcinoma.

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