BackgroundPerineural invasion (PNI) is a malignant metastatic mode of tumors and has been reported in many tumors including esophageal cancer (EC). However, the role of PNI in EC has been reported differently. This systematic review and meta-analysis aims to focus on the role of PNI in EC.MethodsEight databases of CNKI, VIP, Wanfang, Scopus, Wiley, ISI, PubMed, and EBSCO are used for literature search. The association of PNI with gender, pathological stages of T and N (pT and pN), lymphovascular invasion (LVI), lymph node metastasis, 5-year overall survival (OS), and 5-year disease-free survival (DFS) was examined in the meta-analysis by Revman5.0 Software. The pooled OR/HR and 95% CI were used to assess the risk and prognostic value.ResultsSixty-nine published studies were screened for analysis of PNI in EC. The incidence of PNI in esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC) was different, but not statistically significant (p > 0.05). The PNI-positive patients had a significantly higher risk of pT stage (OR = 3.85, 95% CI = 2.45–6.05, p < 0.00001), pN stage (OR = 1.86, 95% CI = 1.52–2.28, p < 0.00001), LVI (OR = 2.44, 95% CI = 1.55–3.85, p = 0.0001), and lymph node metastasis (OR = 2.87, 95% CI = 1.56–5.29, p = 0.0007). Furthermore, the cumulative analysis revealed a significant correlation between PNI and poor OS (HR = 1.37, 95% CI = 1.24–1.51, p < 0.0001), as well as poor DFS (HR = 1.55, 95% CI = 1.38–1.74, p < 0.0001).ConclusionPNI occurrence is significantly related to tumor stage, LVI, lymph node metastasis, OS, and DFS. These results indicate that PNI can serve as an indicator of high malignant degree and poor prognosis in EC.
Drug repositioning is a better way to cancer drug discovery. As a common used oral contraceptive, Levonorgestrel (LNG) was found to play important anticancer roles in several cancers, but its role in human esophageal squamous cell carcinoma (ESCC) was little known. Using ESCC cell line of Ec1 and human normal esophageal epithelial cell line of Het-1A, this study was aim to investigate the effect and molecular mechanism of LNG on the ESCC. The results showed that LNG inhibit the cell proliferation; LNG also induced the cell apoptosis of ESCC related to mitochondrial apoptotic pathway for its disruption of mitochondrial capacity and upregulation of cleaved-Caspase 3 and the declining of the ratio of Bcl-2/Bax; LNG can inhibit the cell migration of ESCC with the E-cadherin overexpression. The anticancer effect of LNG on ESCC mainly associated with Wnt/β-catenin signaling pathway through up-regulation the phosphorylation level of β-catenin. At last, the study declared that LNG combined with cisplatin (CDDP) significantly suppressed the proliferation of Ec1. In conclusions, the LNG serves as efficient anticancer drug in ESCC cells and maybe used for drug repositioning to adjunctive therapy ESCC.
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