The Prognostic Role of Expression of Nectin-4 in Esophageal Cancer

Abstract

Background:Nectin-4 is overexpressed in several human malignant tumors. This study aimed to investigate the expression of Nectin-4 in esophageal cancer tissues compared with adjacent normal esophageal tissue and its association with clinicopathological parameters and prognosis. Material/Methods:Nectin-4 expression in esophageal cancer tissues was compared with adjacent normal esophageal tissue from 94 patients using immunohistochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The chi-squared (c 2 ) test and Fisher's exact test compared categorical variables. The logrank test and Kaplan-Meier survival analysis assessed the relationship between Nectin-4 expression and overall survival (OS). Univariate and multivariate Cox proportional risk models compared Nectin-4 expression, patient prognosis, and clinicopathological parameters. Results:Nectin-4 expression was significantly increased in esophageal cancer tissue compared with normal tissue (P<0.001), tumor size ³4.5 cm, and tumor invasion in T3/T4 compared with T1/T2 stage. Kaplan-Meier survival analysis showed that the OS of patients with increased Nectin-4 expression was significantly reduced compared with patients with low levels of Nectin-4 expression. Patient prognosis in men was less than women, tumor diameter ³4.5 cm, lymph node involvement, and depth of invasion were associated with poor prognosis. Independent prognostic factors were Nectin-4 expression, lymph node involvement, and depth of invasion. Conclusions:In patients with esophageal cancer, the expression levels of Nectin-4, lymph node involvement, and depth of tumor invasion were independent prognostic factors. Further studies should be performed to evaluate the diagnostic and prognostic roles of Nectin-4 and its potential role as a therapeutic target.

Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p

“…It also has a key role in modulating cellular viability and movement capacity [13][14][15][16]. Importantly, an increasing number of studies have demonstrated that Nectin-4 is specifically overexpressed in various cancers [20][21][22]. For example, Challita-Eid et al [35] collected more than two thousand tumor samples containing head/neck, lung, bladder, breast, pancreatic, ovarian, and esophageal tumors; in two-thirds of all specimens obviously high expression of Nectin-4 was detected by IHC staining.…”

“…For example, Challita-Eid et al [35] collected more than two thousand tumor samples containing head/neck, lung, bladder, breast, pancreatic, ovarian, and esophageal tumors; in two-thirds of all specimens obviously high expression of Nectin-4 was detected by IHC staining. Moreover, a large number of studies demonstrated that overexpression of Nectin-4 served as a tumor-associated inducer in various malignant tumors, including colorectal, lung, pancreatic, ovarian, and breast cancers [18][19][20][21][22][23]. Until now, little is known about whether or not Nectin-4 exerts a vital influence on OS oncogenesis and development.…”

“…Nectin 1 ~ 3 is commonly enriched in normal adult tissues, while Nectin-4 was found to be specifically upregulated in various tumors, having a significant role in tumor occurrence and development [15][16][17][18][19][20][21]. Nevertheless, little is known about the role of Nectin-4 protein in OS.…”

“…The Nectin cell adhesion molecule (Nectin) family comprises Nectin-1 ~ 4, which belong to immunoglobulin-semblable transmembrane proteins involved in the Ca 2+ independent adherens junctions (AJs) of cell-cell and have a vital role in enhancing cellular viability and movement ability [15][16][17]. However, numerous studies revealed that Nectin-4 is specifically up-regulated in various cancers, including breast, lung, ovarian, gastric, and pancreatic cancer, and its expression is closely related to tumor oncogenesis and worse prognosis of the patients [18][19][20][21][22][23]. In addition, it has also been reported that Nectin-4 could activate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway and is related to tumor proliferation, metastasis, and angiogenesis in the gallbladder and gastric cancer [24,25].…”

Expression of nectin-4 in papillary renal cell carcinoma

“…Nectin-4 has been identified as a prognostic marker in different cancers such as esophageal, lung, breast and pancreatic cancer [17,18,[20][21][22].…”