Factor In Esophageal Cancer Research Articles

CDC73 serves as a tumour-promoting factor in oesophageal cancer

The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both in vitro and in vivo. Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.

Genetic Impact of HOTAIR, LINC00951, POLR2E and HULC Polymorphisms in Histopathological and Laboratory Prognostic Factors in Esophageal Cancer in the West: A Case-Control Study

Long non-coding RNAs’ HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016, and HULC rs7763881 are progressively reported having a close genetic affinity with esophageal carcinogenesis in the East. Nonetheless, their correlation with variables already endorsed as significant prognostic factors in terms of staging, guiding treatment and predicting recurrence, metastasis, and survival have yet to be explored. Herein, we investigated their prognostic value by correlating them with clinicopathological and laboratory prognostic markers in esophageal cancer in the West. Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated on for esophageal cancer between 2014 and 2018 were compared with 121 healthy community controls. HULC was not detected differently in any of the cancer prognostic subgroups. LINC00951 was underrepresented in Ca19.9 elevated subgroup. HOTAIR was more frequent in both worse differentiation grade and positive Signet-Ring-Cell and Ca19.9 subgroups. POLR2E was identified less frequently in Adenocarcinoma, Signet-Ring-Cell, and Diffuse histologies, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was overrepresented in CEA positive subgroup. These lncRNAs polymorphisms may hold great potential not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk, clinical outcome, and survival. Clinical implications of these findings need to be validated with prospective larger sample-size studies.

Visfatin upregulates VEGF-C expression and lymphangiogenesis in esophageal cancer by activating MEK1/2-ERK and NF-κB signaling.

Lymph node metastasis is a recognized prognostic factor in esophageal cancer. Adipokines, including visfatin, and the molecule vascular endothelial growth factor (VEGF)-C, are implicated in lymphangiogenesis, but whether any association exists between esophageal cancer, adipokines and VEGF-C is unknown. We examined the relevance of adipokines and VEGF-C in esophageal squamous cell carcinoma (ESCC) in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We found significantly higher levels of visfatin and VEGF-C expression in esophageal cancer tissue than in normal tissue. Immunohistochemistry (IHC) staining identified that higher levels of visfatin and VEGF-C expression were correlated with advanced stage ESCC. Visfatin treatment of ESCC cell lines upregulated VEGF-C expression and VEGF-C-dependent lymphangiogenesis in lymphatic endothelial cells. Visfatin induced increases in VEGF-C expression by activating the mitogen-activated protein kinase kinases1/2-extracellular signal-regulated kinase (MEK1/2-ERK) and Nuclear Factor Kappa B (NF-κB) signaling cascades. Transfecting ESCC cells with MEK1/2-ERK and NF-κB inhibitors (PD98059, FR180204, PDTC, and TPCK) and siRNAs inhibited visfatin-induced increases in VEGF-C expression. It appears that visfatin and VEGF-C are promising therapeutic targets in the inhibition of lymphangiogenesis in esophageal cancer.

CircKRT14 upregulates E2F3 by interacting with miR-1256 to act as an oncogenic factor in esophageal cancer.

A growing number of studies have focused on the regulatory role of circular RNAs (circRNAs) in a variety of cancers. The purpose of this study was to investigate the effect of circRNA Keratin 14 (circKRT14) on the progression of esophageal cancer (EC). The levels of circKRT14, miR-1256 and E2F transcription factor 3 (E2F3) were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. The circular structure of circKRT14 was confirmed by RNase R digestion assay. Cell apoptosis, migration and invasion were detected by flow cytometry and transwell assay. The protein levels of related factors were determined by western blot. The relationship between miR-1256 and circKRT14 or E2F3 was verified by dual-luciferase reporter assay. The in vivo function of circKRT14 was studied by xenograft tumor assay. CircKRT14 was significantly increased in EC tissues and cells. CircKRT14 silencing inhibited EC cell proliferation, migration, and invasion, but promoted EC cell apoptosis in vitro. CircKRT1 acted as a sponge for miR-1256 in EC, and in-miR-1256 abolished the inhibitory effect of circKRT14 suppression on EC cell progression. E2F3 was a target of miR-1256 and functioned as an oncogene in EC cells. MiR-1256 curbed EC progression by downregulating E2F3. CircKRT14 could affect E2F3 expression by targeting miR-1256. CircKRT14 regulated EC progression in vivo through miR-1256/E2F3 axis. These results uncovered that circKRT14 up-regulated the expression of E2F3 and promoted the malignant development of EC through sponging miR-1256.

Analysis of Postoperative Hospital Infection Characteristics and Influencing Factors in Esophageal Cancer

Analysis of Postoperative Hospital Infection Characteristics and Influencing Factors in Esophageal Cancer

Nutrition Impact on the Prognosis of Patients with Esophageal Cancer

Obesity is one of the most important risk factors for esophageal cancer. Case-control studies performed in people with body mass index (BMI) over 30 kg/m2 have statistically favorable results for the occurrence of esophageal adenocarcinoma. The purpose of this study is to analyze the role of obesity in the prognosis of patients with squamous cell carcinoma and esophageal adenocarcinoma. The results of the study showed a similar profile of survival curves in patients with squamous cell carcinoma, regardless of the BMI. For patients with esophageal adenocarcinoma, there were statistically significant differences between the BMI value and their survival.

Recurrent metastasis risk factors in esophageal cancer after salvage endoscopic resection for local failure following chemoradiotherapy.

Although salvage endoscopic resection is an optimal treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma, recurrent metastasis (lymph node and/or distant metastasis) after salvage endoscopic resection may occur with a certain degree of unavoidable frequency and is associated with a poor prognosis. However, the risk factors for recurrent metastasis are unclear. This study aimed to evaluate the risk factors for recurrent metastasis after salvage endoscopic resection. Patients who underwent salvage endoscopic resection for local failure after chemoradiotherapy/radiotherapy were analyzed in this single-center, retrospective study. We evaluated the cumulative incidence rates of recurrent metastases, overall survival, and the risk factors for recurrent metastasis after salvage endoscopic resection. We analyzed 132 patients. The 5-year cumulative incidence rate of recurrent metastases after salvage endoscopic resection was 25.7%. The 5-year overall survival rates in all patients and in patients with recurrent metastasis were 66.8% and 22.5%, respectively. Local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy (subdistribution hazard ratio 2.34; P = 0.012) and the presence of lymphatic invasion in salvage endoscopic resection specimen (subdistribution hazard ratio 3.20; P = 0.002) were significant risk factors for recurrent metastasis. Patients with local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy and presence of lymphatic invasion have a high risk for recurrent metastasis. Thus, appropriate surveillance for these patients should be considered.

PO-1287 FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with multimodal therapy

PO-1287 FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with multimodal therapy

PO-1294 clinical prognostic factors for esophageal cancer treated with definitive chemo-radiotherapy

PO-1294 clinical prognostic factors for esophageal cancer treated with definitive chemo-radiotherapy

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Purpose[18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis prediction in different tumors, but its role in esophageal cancer is still debated. The aim of this study was to evaluate the role of semiquantitative baseline PET parameters as possible prognostic and predictive factors in a series of esophageal carcinomas treated with combined modalities.Methods43 patients with esophageal carcinoma were treated with chemoradiotherapy (CRT) followed by surgery in 20 cases and underwent pre-treatment 18F-FDG-PET/CT. Semiquantitative PET parameters were evaluated including Standardized Uptake Value (SUVmax e SUVmean), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) with isocontour of 41 and 50%. Further variables analyzed were gender, primary tumor site, histological type, use of surgery, achievement of a radical resection and the type of chemotherapy regimen. The correlation of all variables with treatment response, loco-regional control (LR), Overall survival (OS) and Disease-Free Survival (DFS) was evaluated.ResultsSUVmax, SUVmean50 and SUVmean41 were significantly higher in node-positive cases and in squamous cell carcinomas. With respect to prognostic factors, MTV was found to be correlated with OS: patients with MTV41 < 11.32 cm3 and MTV50 < 8.07 cm3 (both p values = 0.04) showed better 3-year OS rates (33 vs. 20%). Further factors predicting a better prognosis were the use of surgery and radical resection (R0) (both p values < 0.01).ConclusionsPre-treatment MTV values were significant prognostic factors for OS, together with the use of surgery and R0 resection in esophageal cancers treated with multimodal therapies.

Knockdown of long non-coding RNA SNHG8 suppresses the progression of esophageal cancer by regulating miR-1270/BACH1 axis

ABSTRACT The emerging evidence showed that lncRNAs (long non-coding RNAs) could regulate the progression and affect the malignant behaviors of cancers. LncRNA SNHG8 (small nucleolar RNA host gene 8) has been reported to participate in most cancers development. Here in this study, the role of lncRNA SNHG8 in esophageal cancer was uncovered by a series of functional experiments. The expression pattern of SNHG8 in tumor tissues or cells was first detected by qRT-PCR. Using a lentivirus knockdown shRNA is to repress the expression of SNHG8. Subsequently, the in vitro and in vivo experiments were utilized to evaluate whether the malignant behaviors of esophageal cancer were influenced by knockdown SNHG8. The results indicated that lncRNA SNHG8 should be a cancer-promoting factor with a relatively high expression level in esophageal cancer. Moreover, knockdown SNHG8 inhibited the cell viability and induced cell apoptosis in KYSE30 and TE-1 cells. In addition, based on the results of the binding site analysis and the luciferase reporter system, SNHG8 functions by the miR-1270/BACH1 axis. The follow-up experiments verified that lncRNA SNHG8 could down-regulate the expression of miR-1270 to increase the BACH1 expression. Finally, we confirmed that knockdown SNHG8 retarded the progression of esophageal cancer with a xenograft model. To sum up, our findings suggested that lncRNA SNHG8 is a cancer-promoting factor in esophageal cancer. Knockdown SNHG8 could suppress the progression of esophageal cancer, which implies SNHG8 could be used as a therapeutic target in esophageal cancer.

Identification of Preoperative Fat-Free Mass Index for the Prognosis of Curatively Resected Esophageal Cancer.

The progressive, systemic depletion of muscle mass is a poor prognostic factor for various types of cancers. However, the assessment of body composition for patients with esophagectomy remains unclear. Therefore, we evaluated the significance of the fat-free mass index (FFMI) and estimated the appropriate cutoff value. We compiled clinicopathological characteristics of patients who underwent curative operation for esophageal cancer between October 2013 and March 2018 at Toranomon Hospital and reviewed them until December 2020. We analyzed the short- and long-term outcomes, compared to conventional nutritional factors, and calculated the area under the receiver operating characteristic (ROC) curve. A total of 200 patients were eligible for inclusion. FFMI was ineffective in predicting postoperative complications, with no correlation with other nutritional biomarkers. Preoperative low FFMI led to poor overall survival (OS), and the lower cutoff values based on the time-dependent ROC analysis were 14.4 and 16.8kg/m2 in women and men, respectively. Multivariate analysis for OS revealed that low FFMI (p = 0.010, HR 2.437, 95% CI 1.234-4.815) and clinical stage (p = 0.010, HR 4.781, 95% CI 1.447-15.796) were independent prognostic factors. The 3-year survival rates were 68.9% in low FFMI and 88.6% in normal FFMI. The low FFMI was not predictive of postoperative complications but an independent prognostic factor in esophageal cancer with curative resection, having no correlation with other biomarkers. Our cutoff FFMI values could be useful in selecting the target for muscle improvement programs.

Clinical Significance of Circulating Tumor Cells in Patients with Esophageal Cancer.

In recent years, circulating tumor cells (CTCs) have attracted attention for prediction of metastasis in breast, prostate, and colon cancers. This study aimed to investigate whether detection of CTCs could be prognostic factor in esophageal cancer. This study involved 38 patients treated at Juntendo University from May 2010 to April 2013 who provided consent. CTCs were measured using CellSearch® system in preoperative peripheral blood. Clinicopathological parameters and prognostic factors were retrieved from our medical records. CTCs were detected in 6 of 38 patients (15.8%). Among patients' characteristics and clinicopathological features, CTC-positive group had higher serum SCC levels and tended to have more advanced cStages than the CTC-negative group. The CTC-negative group showed better survival curves than CTCs positive-group in both overall survival (OS) and disease-free survival (DFS) although the differences were not statistically significant. CTCs positivity has a possibility to be prognostic marker according to multivariable analysis of OS and DFS. Although this study has some limitations, our results suggest that CTCs in preoperative peripheral blood has potential to be a prognostic marker for esophageal cancer.

YpN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer

Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

555 VISCERAL OBESITY: PREVALENCE, AND IMPACT ON OPERATIVE AND ONCOLOGIC OUTCOMES IN THE CURATIVE MANAGEMENT OF ESOPHAGEAL CANCER

Abstract Obesity, in particular visceral obesity, is a risk factor for esophageal cancer, but its prevalence and impact on operative and oncologic outcomes is unclear. The aim of this study was to study adipose distribution in esophageal cancer (EC), and to assess its independent impact. Methods 11 consecutive patients undergoing treatment with curative intent for esophageal cancer were studied. Total (TFA), subcutaneous (SFA) and visceral fat areas (VFA), and fat mass (FM), were determined pre-treatment, preoperatively, and 1 year postoperatively. Visceral obesity was defined by CT at L3 as VFA greater than 163.8 cm2 for men and 80.1 cm2 for women. All complications were recorded prospectively, including comprehensive complications index, Clavien-Dindo, and pulmonary complications (PPC). Multivariable logistic and Cox proportional hazards regression were utilized to determine independent predictors of operative and oncologic outcome. Results Visceral obesity (VO) was evident in 290 patients (47.5%), and was associated with BMI-defined obesity, diabetes, metabolic syndrome, Barrett’s esophagus (P = 0.001), well-differentiated tumors (P = 0.027), and lower cN stage (P = 0.012). VO did not impact tumor regression grade (TRG) after neoadjuvant therapy. Postoperatively, VO independently predicted anastomotic leak (P = 0.033, OR2.42 [1.07-5.45]) and pneumonia (P = 0.046, OR1.53 [1.01–2.32]), but not in-hospital mortality (P = 0.466), which was 1% overall. VO was associated with significantly improved overall and disease-specific survival on univariable (P = 0.005, Figure), and multivariable analysis (P = 0.026, 0.74 [0.57–0.97]). In survivorship, VO significantly declined, and was evident in just 15.3% at one year postoperatively. Conclusion VO is linked with Barrett’s associated EC, and less aggressive tumour biology. Although it negatively impacted operative outcomes, VO was associated with improved oncologic outcomes, independent of BMI or fat mass, indicating a distinct biologic phenotype, and highlighting the importance of research elucidating the interaction between the visceral fat microenvironment, metabolic dysfunction, and the tumor microenvironment.

Comorbid early esophageal cancer and Gongylonema pulchrum infection: a case report

BackgroundGongylonema pulchrum is a zoonotic parasite rarely found in humans. To date, there have been no reports on the carcinogenic properties of G. pulchrum, and there are few reports overall on the relationship between esophageal cancer and parasites.Case presentationThis report describes the first case of esophageal gongylonemiasis coexisting with early esophageal cancer. The patient had no high-risk factors for esophageal cancer, such as smoking, flushing after drinking, or tumor history. We speculate the existence of unknown links between esophageal cancer and parasitic infection in this patient.Discussion and conclusionsWe report the first case of a human presenting both esophageal G. pulchrum infection and esophageal squamous cell carcinoma with the hope that it may provide evidence for a new hypothesis of tumorigenesis.

Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study

BackgroundAlcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population.MethodsThis study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer.ResultsOdds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34–3.23) and 0.08 (95% CI: 0.00–0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43–6.34) and 6.18 (95% CI: 1.40–19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption.ConclusionIn Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.

V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as a prognostic biomarker of poor outcomes in esophageal cancer patients

BackgroundEsophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes.MethodsWe used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan–Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models.ResultsThe results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice.ConclusionBRAF overexpression may serve as an effective predictive factor for poor prognosis.

A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma.

Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825–0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860–0.971). This model may facilitate the prediction of LNM in patients with SESCCs.