Development and validation of nomogram based on lncRNA ZFAS1 for predicting survival in lymph node-negative esophageal squamous cell carcinoma patients

Abstract

BackgroundThere is increasing evidence of a relationship between long non-coding RNA (lncRNA) and cancer. This study aimed to examine the prognostic value of the lncRNA ZFAS1 in esophageal squamous cell carcinoma (ESCC).ResultsThe results showed that ZFAS1 expression was significantly higher in ESCC tissues compared with the corresponding adjacent normal tissues (P < 0.001). ESCC patients with high ZFAS1 expression had a poor overall survival (OS). Histological grade, T stage and ZFAS1 expression were integrated to develop the nomogram. The nomogram showed a significantly better prediction of OS for patients with lymph node-negative ESCC. The ROC curve also showed higher specificity and sensitivity for predicting 3- and 5-year ESCC patient survival compared with the AJCC staging system. The decision curve analysis also indicated a greater potential for the nomogram in clinical application compared with the AJCC staging system. Importantly, our findings were supported by a validation cohort.Materials and MethodsWe retrospectively investigated 398 lymph node-negative ESCC patients. Data from the primary cohort (n = 246) were used to develop a multivariate nomogram. The nomogram was internally validated for discrimination and calibration with bootstrap samples and was externally validated with an independent patient cohort (n = 152).ConclusionsOur proposed nomogram, which integrates clinicopathological factors and ZFAS1 expression, can accurately predict the prognosis of lymph node-negative ESCC patients without preoperative chemoradiotherapy.

ZFAS1 functions as an oncogenic long non-coding RNA in bladder cancer

“…Furthermore, Zhou et al [ 27 ] and Pan et al [ 28 ] similarly showed that circulating/serum ZFAS1 levels were significantly associated with clinical stage (TNM stage), lymph node metastasis (N classification), and distant metastasis. In addition, the analogous clinical significance of ZFAS1 was also reported in esophageal squamous cell carcinoma [ 30 ] and ovarian cancer [ 31 ].…”

“…Subsequently, Fan et al [ 18 ] also showed ZFAS1 expression was down-regulated in breast cancer cell lines, and acted as a tumor suppressor in breast cancer. However, ZFAS1 has been suggested to be overexpressed in most types of human cancers such as lung cancer [ 19 ], hepatocellular carcinoma [ 20 ], osteosarcoma [ 21 ], glioma [ 22 , 23 ], colorectal cancer [ 24–26 ], gastric cancer [ 27–29 ], esophageal squamous cell carcinoma [ 30 ], ovarian cancer [ 31 ], prostate cancer [ 32 ], and acute myeloid leukemia [ 33 ]. However, the expression status of ZFAS1 in bladder cancer was still unknown.…”

“…Several meta-analyses were conducted to assess the prognostic value of ZFAS1 in human cancers, and suggested that ZFAS1 high expression might act as a credible factor for unfavorable clinical outcome in various human malignancies [ 34 , 35 ]. In recent years, ZFAS1 high expression has been proven as an unfavorable prognostic biomarker for many types of cancers including lung cancer [ 19 ], hepatocellular carcinoma [ 20 ], osteosarcoma [ 21 ], glioma [ 22 , 23 ], colorectal cancer [ 24 , 25 ], gastric cancer [ 15 ], esophageal squamous cell carcinoma [ 30 ], and ovarian cancer [ 31 ]. There was no study about the prognostic value of ZFAS1 in bladder cancer.…”

Modulation of miR-10a-mediated TGF-β1/Smads signaling affects atrial fibrillation-induced cardiac fibrosis and cardiac fibroblast proliferation

“…In a study by He et al [45], Smad7 down-regulation could promote TGF-β1-mediated cardiac fibrosis, which is one of the major mechanisms of cardiac fibrosis. Liu et al also reported that osthol treatment could alleviate TGF-β1-induced cardiac fibrosis with increased Smad7 expression and reduced collagen I/III ratios and α-SMA and ECM deposition [46]. Importantly, He et al [47] found that miR-21 could down-regulate Smad 7 to enhance TGF-β1/Smad signaling and promote AF-induced cardiac fibrosis.…”

Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications

“…Additionally, the dysregulation of lncRNAs ATB [ 51 ], XIST [ 74 ], AK001796 [ 93 ], MALAT1 [ 147 ], nuclear transcription factor NF-κB interacting lncRNA (NKILA) [ 162 ], SPRY4-IT1 [ 163 ], and zinc finger antisense 1 (ZFAS1) [ 164 ] has also been demonstrated to be markedly associated with advanced lymph node metastasis, aggressive TNM stage, and shorter survival time. These lncRNAs may also serve as potential prognostic biomarkers for EC.…”