Objective To observe the growth of orthotopic transplanted tumor in nude mice after stomatin-like protein 2 (SLP-2) expression decreased, and to further study the role of SLP-2 in the development and progression of esophageal squamous cell carcinoma. Methods Using RNA interference technique, esophageal squamous cell carcinoma cell lines with specific expression of SLP-2 and stable expression of luciferase were established. The healthy female nude mice with weight ranging from 19 to 22 g were randomly divided into 3 groups (n=12), 6 mice were used to establish subcutaneous xenografts, and the other 6 mice were used to establish the orthotopic transplanted tumor model (Group 1: cell infected with SLP-2-1 plasmid; group 2: cell infected with SLP-2-2 plasmid; group 3: cell infected with SHGFP plasmid). Index of the experiment end was weight loss and poor general situation in any mouse. Before the nude mice were sacrificed, the luciferase value of the tumor was detected by using in vivo imaging technique. After the nude mice were sacrificed, the primary tumor was removed for pathology examination. Results There was no significant difference in region of interest (ROI) value between the group 1 and group 2 (P=0.943). The ROI value for both groups 1 and 2 was significantly lower than that in the group 3 (P=0.002, P=0.000). The primary tumor infiltrated into the muscularis propria of esophageal was observed in all groups. Conclusion SLP-2 is involved in the development and progression of esophageal squamous cell carcinoma, and the decrease of SLP-2 expression can inhibit the growth of esophageal squamous cell carcinoma.
ObjectiveTo establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis.MethodsRNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models.ResultsThe risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC.ConclusionThe ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.
ObjectiveTo explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC).MethodsThe clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. ResultsA total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557).ConclusionThere is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.
Objective To investigate whether postoperative therapy can bring survival benefits to patients with locally advanced esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen. Methods We retrospectively reviewed clinical data of 115 patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy with TP regimen and underwent esophagectomy in our hospital from January 2007 through December 2016. Patients were divided into two groups including a non-receiving treatment group (54 patients with 47 males and 7 females) and a receiving treatment group (61 patients with 52 males and 9 females). There were 31 patients with postoperative chemotherapy, 14 with postoperative radiotherapy, and 16 with postoperative chemotherapy and radiotherapy in the receiving treatment group. Results In the non-receiving treatment group, the 5-year median disease free survival (DFS) rate was 54.7%, and the 5-year overall survival (OS) rate was 55.3%. In the receiving treatment group, the median DFS was 46.0 months (95% CI 22.9–69.1), the 5-year DFS rate was 42.3%; and the median OS was 68.0 months (95% CI 33.0–103.0), the 5-year OS rate was 51.3%. Furthermore, there was no statistical difference between the two groups with regards to DFS (P=0.641) or OS (P=0.757) using Kaplan-Meier method. Besides, in each subgroup, the results of Cox proportional hazard model analysis showed postoperative treatment did not improve survival (P>0.05, respectively). Conclusion Postoperative treatment does not bring survival benefits to patients with esophageal squamous cell carcinoma who have received neoadjuvant chemotherapy with TP regimen.
ObjectiveTo investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia inducible factor-1α (HIF-1α). MethodsWestern blotting and quantitative polymerase chain reaction (qPCR) were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. ResultsCompared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. ConclusionUp-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.
ObjectiveTo investigate the pan-cancer expression profile, prognostic value, co-expression networks, immune regulatory roles of BRF1, and its biological functions and molecular mechanisms in esophageal squamous cell carcinoma (ESCC). MethodsIntegrated analysis of TCGA pan-cancer datasets was performed to evaluate BRF1 expression differences between tumor/normal tissues, survival correlations, co-expressed gene-enriched pathways, and immune features (immune checkpoints, cytokines, immune cell infiltration). GEO datasets were used to validate BRF1 expression in ESCC. BRF1 was knocked down using siRNA in ESCC cells, with MTT and Transwell assays assessing proliferation/migration, and Western blot analyzing proliferation- (PCNA) and migration-related proteins (Vimentin, MMP, E-Cadherin). TCGA data were analyzed to explore BRF1-ferroptosis correlations. ResultsBRF1 was significantly upregulated in over 20 cancer types. High BRF1 expression predicted poor prognosis in adrenocortical carcinoma (ACC) and prostate adenocarcinoma (PRAD). BRF1 positively regulated T cell-mediated cell death pathways in ESCA and circadian rhythm pathways in PAAD. BRF1 exhibited cancer-type-specific correlations with immune checkpoints, cytokine networks, and immune cell infiltration. In vitro, BRF1 knockdown suppressed ESCC proliferation (PCNA downregulation) and migration (Vimentin/MMP downregulation, E-Cadherin upregulation). BRF1 expression positively correlated with ferroptosis antagonists (GPX4, HSPA5, SLC7A11). ConclusionBRF1 demonstrates complex pan-cancer expression and functional heterogeneity, modulating tumor progression and immune infiltration. BRF1 promotes ESCC proliferation and migration, potentially via ferroptosis resistance regulation, highlighting its potential as a therapeutic target in ESCC.
Objective To evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.
Objective To investigate the prognostic value of preoperative plasma fibrinogen (FIB) combined with lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of patients with esophageal squamous cell carcinoma. Methods A retrospective analysis was conducted on patients who underwent esophagectomy in our hospital from January 2015 to December 2018. Based on the cut-off values of preoperative FIB and LMR, The F-LMR scoring system was constructed, and patients were divided into three groups. Kaplan-Meier analysis was used to assess 5-year overall survival and 5-year progression free survival, and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Results Finally 260 patients were collected, including 237 males and 23 females, with a median age of 64 years (ranging from 59 to 70 years). The 5-year OS rates for patients with F-LMR score of 0, 1, and 2 were 24.44%, 51.69%, and 67.31%, respectively, and the 5-year PFS rates were 15.56%, 42.37%, and 57.62%, respectively. Lower preoperative F-LMR scores were associated with worse prognosis. Multivariate analysis showed that deeper tumor invasion, presence of lymph node metastasis, larger tumor maximum diameter, and lower preoperative F-LMR score were independent prognostic factors for OS. Conclusion The F-LMR score system based on the preoperative FIB and LMR can serve as an effective tool for predicting the prognosis of patients with esophageal squamous cell carcinoma.
Objective To investigate the influencing factors for the clinical remission of advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy, establish an individualized nomogram model to predict the clinical remission of advanced ESCC with neoadjuvant chemotherapy and evaluate its efficacy, providing serve for the preoperative adjuvant treatment of ESCC.Methods The clinical data of patients with esophageal cancer who underwent neoadjuvant chemotherapy (nedaplatin 80 mg/m2, day 3+docetaxel 75 mg/m2, day 1, 2 cycles, 21 days per cycle interval) in the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from February 2016 to August 2020 were analyzed retrospectively. According to the WHO criteria for efficacy assessment of solid tumors, tumors were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). CR and PR were defined as effective neoadjuvant chemotherapy, and SD and PD were defined as ineffective neoadjuvant chemotherapy. Univariate and multivariate analyses were used to analyze the influencing factors for the short-term efficacy of neoadjuvant chemotherapy. The R software was used to establish a nomogram model for predicting the clinical remission of advanced ESCC with neoadjuvant chemotherapy, and Bootstrap method for internal verification of the model. C-index, calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the nomogram.Results Finally 115 patients were enrolled, including 93 males and 22 females, aged 40-75 (64.0±8.0) years. After receiving docetaxel+nedaplatin neoadjuvant chemotherapy for 2 cycles, there were 9 patients with CR, 56 patients with PR, 43 patients with SD and 7 patients with PD. Among them, chemotherapy was effective (CR+PR) in 65 patients and ineffective (SD+PD) in 50 patients, with the clinical effective rate of about 56.5% (65/115). Univariate analysis showed that there were statistical differences in smoking history, alcoholism history, tumor location, tumor differentiation degree, and cN stage before chemotherapy between the effective neoadjuvant chemotherapy group and the ineffective neoadjuvant chemotherapy group (P<0.05). Logistic regression analysis showed that low-differentiation advanced ESCC had the worst clinical response to neoadjuvant chemotherapy, moderately-highly differentiated ESCC responded better (P<0.05). Stage cN0 advanced ESCC responded better to neoadjuvant chemotherapy than stage cN1 and cN2 (P<0.05). The C-index and the area under the ROC curve of the nomogram were both 0.763 (95%CI 0.676-0.850), the calibration curve fit well, the best critical value of the nomogram calculated by the Youden index was 70.04 points, and the sensitivity and specificity of the critical value were 80.0% and 58.0%, respectively.ConclusionThe established clinical prediction model has good discrimination and accuracy, and can provide a reference for individualized analysis of the clinical remission of advanced ESCC with neoadjuvant chemotherapy and the screening of new adjuvant treatment subjects.
ObjectiveTo evaluate the clinical outcomes of larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction for the treatment of cervical esophageal squamous cell carcinoma (ESCC) without tumor involvement of the larynx and hypopharynx compared with the upper thoracic ESCC.MethodsRetrospective and comparative analysis of consecutive patients with cervical and upper thoracic ESCC who underwent R0 surgical resection from 2006 to 2011 in our center was performed. Kaplan-Meier method was used to calculate the patients’ survival.ResultsIn total, 44 pairs of patients, including 71 males and 17 females with an average age of 60.66±8.49 years were enrolled in the study after propensity score matching. The baseline characteristics of the two groups of patients were well balanced. There was no statistical difference in the operation time (P=0.100), blood loss (P=0.685), mortality rate in 30 days (P=1.000), total complication rate (P=0.829), cervical anastomosis leakage (P=0.816), mechanical ventilation (P=1.000), normal oral diet within 15 days (P=0.822) and anastomosis recurrence rate (P=0.676) between the two groups. Survival analysis showed that there was no statistical difference in survival time between the cervical group [31.83 (95%CI 8.65-55.02) months] and upper thoracic group [37.73 (95%CI 25.29-50.18) months, P=0.533]. The 5-year survival rates were 32.6% and 42.1%, respectively.ConclusionLarynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction for the treatment of cervical ESCC without involvement of the larynx and hypopharynx may result in a similar clinical outcome to upper thoracic ESCC.