Clinical significance of YAP1 and TAZ in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the eighth most frequent and sixth most fatal cancer worldwide. This study aimed to investigate the clinical characteristics and prognostic significance of yes related protein 1 (YAP1) and transcriptional co-activator with PDZ binding motif (TAZ) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 306 ESCC pathological specimens and adjacent tissues (as control; tissues from the esophageal mucosa >5 cm from the edge of the tumor) were collected between January, 2008 and December, 2018. Immunohistochemical staining was used to assess the expression of YAP1 and TAZ proteins in the ESCC and adjacent tissues, and their relationship with clinicopathological parameters was evaluated using SPSS 21.0 software. RESULTS: YAP1 and TAZ proteins were highly expressed in ESCC, and their expression was closely related to TNM stage and lymph node metastasis. Expression of YAP1 was associated with tumor size (P = .029), differentiation (P = .000), depth of invasion (P = .001), and TNM stage (P = .000). Expression of TAZ was associated with tumor size (P = .034), differentiation (P = .000), depth of invasion (P = .029), lymph node metastasis (P = .006), and ethnicity (P < .001). The expression of YAP1 protein was positively correlated with the expression of TAZ protein (r = 0.257, P < .05). YAP1 and TAZ expression (P = .039 and .000, respectively), tumor size (P = .041), and lymph node metastasis (P = .001) significantly affected the overall survival of patients with ESCC, and represent independent factors for overall survival. CONCLUSION: YAP1 and TAZ proteins are highly expressed in ESCC, and closely related to the clinical and pathological parameters such as the diameter of the tumor, degree of differentiation, and depth of invasion, indicating that YAP1 and TAZ may be involved in the development of ESCC. YAP1 and TAZ may be used as prognostic markers in ESCC.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

Investigation of IL-4, IL-10, and HVEM polymorphisms with esophageal squamous cell carcinoma: a case-control study involving 1929 participants.

It is believed that an individual's hereditary factors may be involved in the development of esophageal cancer (EC). The present study recruited 721 esophageal squamous cell carcinoma (ESCC) cases and 1208 controls and explored the roles of single nucleotide polymorphisms (SNPs) in the interleukin-4 (IL-4), IL-10, and herpesvirus entry mediator (HVEM) genes in contributing to ESCC risk. IL-4, IL-10, and HVEM SNPs were analyzed by employing an SNPscan method. After adjustment for body mass index (BMI), smoking, drinking, age and gender, we identified that the rs2070874 T>C locus in IL-4 gene decreased the risk of ESCC (CC vs. TT: P=0.008; CC vs. TT/TC: P=0.010). After a stratified analysis, we suggested that the IL-4 rs2070874 T>C variants might be a protective factor for ESCC in male, ≥63 years old, never smoking, drinking and BMI < 24 kg/m2 subgroups. In addition, we identified that the rs2243263 G>C polymorphism in IL-4 gene was a risk factor for ESCC development in the BMI ≥ 24 kg/m2 subgroup (GC vs. GG: P=0.030 and GC/CC vs. GG: P=0.018). We identified an association of the IL-4 rs2070874 T>C SNP with the decreased susceptibility of ESCC in stage I/II subgroup. Finally, we found an association of the IL-10 rs1800872 T>G SNP with a worse differentiation (TG vs. TT: P=0.048 and GG/TG vs. TT: P=0.032). In conclusion, the findings indicate a potential importance of IL-4 rs2070874 T>C, IL-4 rs2243263 G>C and IL-10 rs1800872 T>G SNPs in the development of ESCC.

Presentation, Treatment, and Outcomes of Vulnerable Populations With Esophageal Cancer Treated at a Safety-Net Hospital.

Social determinants of health have been associated with poor outcomes in esophageal cancer. Primary language and immigration status have not been examined in relation to esophageal cancer outcomes. This study aims to investigate the impact of these variables on stage of presentation, treatment, and outcomes of esophageal cancer patients at an urban safety-net hospital. Clinical data of patients with esophageal cancer at our institution between 2003 and 2018 were reviewed. Demographic, tumor, and treatment characteristics were obtained. Outcomes included median overall survival, stage-specific survival, and utilization of surgical and perioperative therapy. Statistical analysis was conducted using Chi-square test, Fisher's exact tests, Kaplan-Meier method, and logistic regression. There were 266 patients; 77% were male. Mean age was 63.9 years, 23.7% were immigrants, 33.5% were uninsured/Medicaid, and 16.2% were non-English speaking. Adenocarcinoma was diagnosed in 55.3% and squamous cell in 41.0%. More patients of non-Hispanic received esophagectomies when compared to those of Hispanic origin (64% vs 25%, P = 0.012). Immigrants were less likely to undergo esophagectomy compared to US-born patients (42% vs 76%, P = 0.001). Patients with adenocarcinoma were more likely than squamous cell carcinoma patients to undergo esophagectomy (odds ratio = 4.40, 95% confidence interval 1.61-12.01, P = 0.004). More commercially/privately insured patients (75%) received perioperative therapy compared to Medicaid/uninsured (54%) and Medicare (49%) patients (P = 0.030). There was no association between demographic factors and the utilization of perioperative chemoradiation for patients with operable disease. Approximately 23% of patients with operable disease were too frail or declined to undergo surgical intervention. In this small single-center study, race and primary language were not associated with median survival for patients treated for esophageal cancer. US-born patients experienced higher surgical utilization and privately insured patients were more likely to receive perioperative therapy. Many patients with operable cancer were too frail to undergo a curative surgery. Studies should expand on the relationships between social determinants of health and nonclinical services on delivery of care and survival of vulnerable populations with esophageal cancer.

[Expression pattern of FAM135B and K (lysine) acetyltransferase 5 in esophageal squamous cell carcinoma in Uygur patients].

OBJECTIVE: To explore the expression of the family with sequence similarity 135 member B (FAM135B) and K(lysine) acetyltransferase 5 (KAT5) in esophageal squamous cell carcinoma (ESCC) in Uygur patients. METHODS: The expression of FAM135B and KAT5 in ESCC tissues and paired adjacent tissues from 40 Uygur patients were detected using Roche Benchmark XT. The correlation of FAM135B and KAT5 and their correlation with the clinicopathological characteristics of the patients were analyzed. RESULTS: The positivity rates of FAM135B and KAT5 in ESCC tissues were 92.50% (37/40) and 15.00%(6/40) in these patients, respectively. The ESCC tissues showed a significantly higher rate of strong FAM135B expression than the adjacent tissues [45.00% (18/40) vs 22.50% (9/40); Χ2=4.528, P=0.033], but the rates of negative KAT5 expression was similar between ESCC and adjacent tissues [85.00% (34/40) vs 87.50% (35/40); Χ2=0.105, P=0.745]. Strong expressions of FAM135B in ESCC tissues and the paired adjacent tissues were well correlated (Kendall's coefficient = 0.707, P<0.001). In ESCC tissues, a strong expression of FAM135B showed a significant negative correlation with KAT5 expression (Kendall's coefficient=-0.946, P<0.001). Neither FAM135B nor KAT5 expression was associated with the patients' gender, age, tumor site, tumor differentiation, invasion, lymph node metastasis and clinical stage (all P>0.05). CONCLUSION: A strong expression of FAM135B may be an important molecular basis for the occurrence of ESCC in Uygur patients and plays its role by negatively regulating the expression of KAT5.