Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Mechanism study of lncRNA RMRP regulating esophageal squamous cell carcinoma through miR-580-3p/ATP13A3 axis.

OBJECTIVE: It is well-known that lncRNAs regulate energy metabolism in tumors. This study focused on the action of RMRP on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis, and glycolysis. METHODS: In the resected ESCC tissues and adjacent tissues from patients, RMRP/miR-580-3p/ATP13A3 expressions were evaluated. ESCC cell proliferation rates and apoptotic rates were measured by CCK-8 and flow cytometry, respectively. Apoptosis related markers were examined by Western blot. Moreover, glucose uptake, lactic acid, and ATP were measured by commercial kits, whereas HK2 and PKM2 were evaluated by Western blot to study ESCC cell glycolysis. Finally, the editing program of RMRP/miR-580-3p/ATP13A3 was translated by luciferase reporter assay and RIP analysis. RESULTS: RMRP and ATP13A3 were induced, while miR-580-3p was reduced in their expression in ESCC tissues. Silencing RMRP reduced proliferation, glycolysis, and anti-apoptosis ability of ESCC cells. RMRP sequestered miR-580-3p to target ATP13A3. Silenced ATP13A3 or overexpressed miR-580-3p rescued overexpressed RMRP-mediated promotion of proliferation, glycolysis, and anti-apoptosis of ESCC cells. CONCLUSION: RMRP accelerates ESCC progression through the miR-580-3p/ATP13A3 axis, renewing a reference for lncRNA-based therapies for tumors.

MYLK and CALD1 as molecular targets in bladder cancer.

Bladder cancer (BC) is a malignant tumor that occurs in bladder mucosa. However, relationship between myosin light chain kinase (MYLK) and CALD1 and BC remains unclear. The BC datasets GSE65635 and GSE100926 were downloaded from gene expression omnibus by GPL14951 and GPL14550. Multiple datasets were merged and batched. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome analysis, gene set enrichment analysis, immune infiltration analysis, survival analysis and Comparative Toxicogenomics Database were performed. TargetScan screened miRNAs that regulated central DEGs. 1026 DEGs were identified. According to GO analysis, DEGs were mainly enriched in cancer pathway, cGMP-PKG signaling pathway, Apelin signaling pathway and proteoglycans in cancer. The enrichment items are similar to GO and Kyoto Encyclopedia of Gene and Genome enrichment projects for DEGs, which were mainly enriched in cancer pathways and leukocyte trans-endothelial cell migration. Among enrichment projects of metascape, GO has regulation of the enzyme-linked receptor protein signaling pathway and silk-based process, as well as an enrichment network stained by enrichment terms and P values. Nine core genes (ACTA2, MYLK, MYH11, MYL9, ACTG2, TPM1, TPM2, TAGLN and CALD1) were obtained, which were highly expressed in tumor tissue samples and lowly expressed in normal tissue samples. Nine genes were associated with necrosis, inflammation, tumor, edema, and ureteral obstruction. MYLK and CALD1 are highly expressed in the BC. The higher expression of MYLK and CALD1, the worse prognosis.

Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency.

Esophageal cancer (EC) threatens many lives in China, especially in areas with high incidences of EC. Our previous studies proved that zinc deficiency (ZD) promotes the cell cycle, thus promoting the progression of EC in areas with a high incidence of EC. Artesunate could inhibit the cell cycle, thereby inhibiting the progression of EC. In this study, we first demonstrated the mechanism by which artesunate inhibits EC in vitro and then demonstrated that artesunate could reverse the ZD-promoted progression of EC before EC occurred in vivo. The results showed that artesunate could inhibit the cell cycle, metastasis, and glycolysis of EC cells. Artesunate could target HK1, promote HK1 degradation, and reduce the levels of HIF-1α and PKM2 expression, which are key glycolysis enzymes. The in vivo results showed that ZD could increase the expression of HK1 and increase the incidence of EC. Artesunate reduced the incidence of EC and decreased the level of HK1 expression before EC occurred. Artesunate has an anti-EC effect by inhibiting aerobic glycolysis and has the potential to be a drug that prevents EC in areas with a high risk of EC.

Clinicopathological Features and Prognoses in Patients With Brain Metastases From Small-Cell Esophageal Carcinoma: A Retrospective Analysis of 18 Patients.

Objective: This study aims to examine the clinical characteristics of patients with brain metastases (BM) from small-cell esophageal carcinoma (SCEC) and to explore the association of the corresponding factors with overall survival (OS). Methods: The data of 18 patients with brain metastases from SCEC, diagnosed from January 1, 2006, to December 31, 2018, in the Fourth Hospital of Hebei Medical University were analyzed retrospectively. Results: The 18 patients who were included in this study accounted for 6.7% of the patients with SCEC diagnosed from 2006 to 2018. Of the 18 patients, 8 (44.4%) were females. For the entire cohort, the median OS was 7 months, the 1-year OS was 22.2%, and the 2-year OS was 0%. For patients who received whole-brain radiotherapy (WBRT) and for those who did not (13 vs. 5), the median OS was 11.9 and 3 months, respectively, and the 1-year OS was 30.8 and 0%, respectively. When comparing diagnosis-specific Graded Prognostic Assessment (DS-GPA) scores of patients with BM from SCEC ranging from 2.5 to 4 and from 0 to 2, the median OS was 13.1 and 4 months, respectively, and the 1-year OS was 57.1 and 0%, respectively. In the univariable regression, patients who received WBRT had improved OS compared to those who did not (HR = 0.249, p = 0.018), and patients with a DS-GPA score of 2.5-4 were associated with improved OS compared with patients with a DS-GPA score of 0-2 (HR = 0.050, p = 0.005). Conclusion: The incidence of brain metastases in patients with SCEC is low, but the prognosis in those patients is very poor. The DS-GPA score may be a prognostic factor of patients with BM from SCEC. Brain radiotherapy could improve the survival of these patients.

MiR-139-5p regulates VEGFR and downstream signaling pathways to inhibit the development of esophageal cancer.

BACKGROUND: MiR-139-5p plays a significant role in tumorigenesis, metastasis and recurrence, suggesting that it may potentially be used as a promising biomarker for esophageal cancer diagnosis, prognosis and therapy. This study aimed to investigate the role and the mechanism of miRNA-139-5p in esophageal cancer. METHODS: This study included 11 patients from an area with a high incidence of esophageal cancer. The expression levels of miRNA-139-5p in esophageal cancer tissues and para-carcinoma tissues of 11 patients were measured. We examined the expression of miR-139-5p in serum obtained from 92 consecutive patients from Cixian, which is a region in Hebei Province with a high rate of histologically confirmed esophageal cancer. The expression of miR-139-5p in esophageal cancer cell lines was detected. In the KYSE150 cell line with the lowest expression level of miR-139-5p, we transfected a plasmid to upregulate the expression level and examined the role of miR-139-5p in esophageal squamous cell carcinoma proliferation, migration and invasion. We conducted a gene profiling study using miR-139-5p cell lines to detect the expression of significant genes related to tumor progression, including cyclinD1, E-cadherin and VEGFR-1. We then constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites to investigate the target. RESULTS: MiRNA-139-5p expression levels in esophageal cancer tissues from 11 patients were significantly higher than those in para-carcinoma tissues. MiR-139-5p expression in the serum of 92 patients with esophageal cancer was associated with gender (P = 0.039) and TNM stage (P = 0.015). Factors that were not correlated with miR-139-5p expression were age (P = 0.293), smoking history (P = 0.397), length of tumor (P = 0.309), width of tumor (P = 0.296), depth of tumor (P = 0.724), lymphoma metastasis (P = 0.531) and postoperative therapy (P = 0.884). MiR-139-5p (P = 0.013) correlated significantly with observed survival rates. The lymphoma metastasis (P = 0.005) and TNM stage (P = 0.000) were significantly associated with observed survival rates. However, no significant relationships were found between the miR-139-5p and patient characteristics including gender, age, smoking history, tumor size and postoperative therapy. In the KYSE150 cell line, the expression level of miR-139-5p was the lowest. We transfected a plasmid to upregulate the expression level and found that the cell proliferation, metastasis and invasion abilities decreased. Upregulation of miR-139-5p inhibited the expression of Cyclin D1 and VEGFR-1 and increased the expression of E-cadherin. For further confirmation, we constructed luciferase reporters containing miR-139-5p, which contained wild-type (WT) or mutated-type (Mut) VEGFR-1 binding sites for target investigation. The results show that the corresponding VEGFR-1-Mut construct no longer suppressed miR-139-5p. CONCLUSIONS: MiR-139-5p may be a novel therapeutic target and prognostic biomarker of esophageal cancer.

Comparison of elective nodal irradiation and involved-field irradiation in esophageal squamous cell carcinoma: a meta-analysis.

It remains controversial whether radical radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) still requires elective nodal irradiation (ENI), or only involved-field irradiation (IFI). In this study, a meta-analysis was conducted to compare ENI and IFI in the treatment of ESCC, in order to provide guidance for clinical practice. Literature on the use of ENI and IFI in the treatment of ESCC was retrieved, and the last access date was 31 December 2017. A meta-analysis was performed to evaluate the relative advantages and disadvantages of using ENI and IFI. Ten studies, involving a total of 1348 patients, were included in this analysis; of these, 605 patients underwent radiotherapy only, and 743 underwent radiochemotherapy. There was no significant difference in the 1-, 2- or 3-year local control rates between ENI and IFI, or in the 1-, 2- or 3-year overall survival rates. However, the incidences of ≥Grade 3 acute esophagitis and pneumonia were significantly lower in the IFI group. There were no differences in the rates of ≥Grade 3 myelosuppression or of out-field recurrence or metastasis between these two groups. Thus, neither local control rates nor overall survival rates differed significantly between the ENI and IFI groups, but in the latter group, incidences of severe radiation esophagitis and pneumonia were significantly lower. IFI was not associated with an increase in out-field recurrence or metastasis.

[Lymph node metastasis patterns and influencing factors in patients with limited esophageal small cell carcinoma].

OBJECTIVE: To explore the patterns and influencing factors of lymph node metastasis in limited esophageal small cell carcinoma (PESCC). METHODS: A total of 98 limited stage PESCC patients who underwent surgery were selected for this study. The lymph node metastasis ratio at different sites, depth of invasion, tumor length and other factors were analyzed to assess their influence on lymph node metastasis. RESULTS: Among the 98 PESCC cases, 46 cases had lymph node metastasis (46.9%). 100 out of 833 lymph nodes had metastasis, with a metastasis ratio of 12.0%. For upper thoracic esophageal small cell carcinomas, lymph node metastasis ratios were 42.9%, 12.5%, 0 and 0 in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity, respectively. In the middle thoracic PESCCs, the lymph node metastasis ratios were 18.8%, 7.7%, 15.7%, and 15.3%, respectively. In the lower thoracic PESCCs, the lymph node metastasis ratios were 0, 0, 27.3% and 23.5%, respectively. Lymph node metastasis rates in PESCCs at stages T1, T2, T3, T4 were 15.4%, 42.3%, 63.9%, and 80.0%, respectively. The lymph node metastasis ratios in PESCCs at stages T1, T2, T3, T4 were 2.0%, 8.3%, 17.8% and 25.0%, respectively. Lymph node metastasis rate and lymph node metastasis ratio at different T stages were of significant difference (P<0.05 for all). Lymph node metastasis rates in patients with tumor <3 cm, 3-5 cm, and >5 cm were 30.6%, 46.9% and 66.7%, respectively, and lymph node metastasis ratios were 5.4%, 11.0% and 21.1%, respectively. Lymph node metastasis rate and lymph node metastasis ratio in patients with different tumor length had significant differences (P<0.05 for all). Lymph node metastasis ratio was 11.6% in the Chr-A negative and weak positive group, much higher than 4.3% in the Chr-A positive group (P=0.013). There was a tendency that lymph node metastasis ratio of NSE-positive group was higher than that of NSE-negative and weak positive group (P=0.069). The logistic univariate analysis did not find high risk factors of distant lymph node metastasis (all P>0.05). Logistic multivariate analysis found that only depth of invasion was a risk factor of lymph node metastasis in limited PESCC (P=0.002). CONCLUSIONS: Esophagus small cell carcinomas sometimes have early lymph node metastases in many sites and distant range. The middle thoracic PESCCs tend to have extensive metastasis quite common in the upper mediastinal lymph nodes. Lower mediastinal and abdominal lymph node metastases are often seen in lower thoracic PESCCs. The depth of invasion and tumor length are main factors influencing mediastinal lymph node metastasis. The depth of invasion is an independent risk factor for lymph node metastasis.

[Relationship between hypoxia inducible factor-1α and esophageal squamous cell carcinoma: a meta analysis].

OBJECTIVE: To explore the expression of hypoxia inducible factor-1α(HIF-1α) in esophageal squamous cell carcinoma and its correlation with clinicopathological features. METHODS: Original literatures in foreign languages regarding correlation between HIF-1α and esophageal squamous cell carcinoma were identified from Cochrane Library, PubMed, EMbase database, and Chinese original literatures were from CBM, CNKI. All analyses were performed by Stata 11.0 software. Histological grade, degree of differentiation, T stage, lymph node metastasis, tumor stage, lymphatic invasion and vascular invasion were analyzed using pooled odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 14 studies including 1 121 patients were enrolled in this meta analysis. Comparing with normal tissue, the expression of HIF-1α in esophageal squamous cell carcinoma was significantly enhanced (OR = 0.088, 95% CI: 0.061-0.129, P = 0.000); HIF-1α was significantly associated with T stage and lymph node metastasis (OR = 0.421, 95% CI: 0.222-0.798, P = 0.008; OR = 0.387, 95% CI: 0.207-0.725, P = 0.003). High expression of HIF-1α was correlated with an increased depth of tumor invasion, more lymph node metastasis and advanced tumor stage, whereas there was no relation to the degree of differentiation, histological grade, tumor stage, lymphatic invasion and vascular invasion. CONCLUSIONS: High expression of HIF-1α protein correlates with an increased risk of esophageal squamous cell carcinoma. HIF-1α may be an indicator for T stage, lymph node metastasis and tumor stage, but further studies are needed.

Relationship between EGFR over-expression and clinicopathologic characteristics in squamous cell carcinoma of the esophagus: a meta-analysis.

Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1,150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.