Cutaneous squamous cell carcinoma (cSCC) is the second most common human skin tumor. In recent years, the incidence of cSCC is increasing annually. Although most cSCC is curable after basic treatment, the advanced cSCC progresses rapidly and poses a significant risk for the impact on quality of life and death. In 2017, the latest version of cSCC management guideline was developed by the American Academy of Dermatology (AAD) based on extensive evidence-based medical evidence, including cSCC biopsy techniques, histopathological assessment, clinical staging and grading, surgical and nonsurgical treatment, follow-up, recurrence prevention, and management of the advanced cSCC. The purpose of this article is to briefly introduce and interpretate this guideline.
ObjectiveTo systematically review the correlation between the expression of cytokeratin 19 (CK19) and oral squamous cell carcinoma (OSCC). MethodsPubMed, EMbase, CJFD, CBM, CNKI, VIP, WanFang Data and The Cochrane Library (Issue 1, 2015) were electronically searched from inception to January 1st 2015 to collect case-control studies about the correlation between CK19 expression and clinical pathogenic features in OSCC. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of 11 studies were included, involving 612 OSCC cases and 564 normal controls. The results of meta-analysis showed that:The expression levels of CK19 were significantly different between the OSCC group and the control group, between OSCC groups with and without lymph node metastasis, between the high differentiation group and the middle/poor differentiation group, and between the clinical stage I group and the clinical stages Ⅱ to Ⅲ group (all P values≤0.05). However, there were no significant differences in expression levels of CK19 between the male OSCC group and the female OSCC group, and between the carcinoma size T1/T2 group and the T3/T4 group (all P values >0.05). ConclusionCurrent evidence shows that, CK19 expression may be associated with the occurrence, development and transfer of OSCC, and may be positively corrected with tumor malignance. It may be an indicator of poor prognosis and can be considered as a molecular marker of OSCC.
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.
ObjectiveTo explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma.MethodsPicture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis.ResultsAccording to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra.ConclusionBioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.
Objective To explore the role of versican (VCAN) in ESCC prognosis based on bioinformatics data. MethodsFirst, three RNA microarray datasets of ESCC were downloaded from GEO database, which were then integrated and used to explore differentially expressed genes (DEGs). The subsequent analysis was conducted based on the results of these DEGs: (1) The STRING database was used to construct a protein-protein interaction (PPI) network; (2) molecular complex detection software was used to analyze the modules of the PPI network, of which the most significant modules were chosen, and hub genes were the genes included in the chosen modules; (3) high-throughput RNA sequencing data from TCGA and GTEx databases were used to verify the expression of these hub genes to confirm whether they were differentially expressed; (4) the survival curve analysis of confirmed DEGs was conducted to select genes that had significant influence on the survival of ESCC; (5) TIMER database was used to analyze the relationship between the gene expression of VCAN and the abundance of tumor-infiltrating immune cells (TIICs) and gene markers in these cells; (6) Targetscan and miRDB software were used to predict the miRNAs that could regulate VCAN, and Cytoscape software was used to construct the regulatory network. ResultsA total of 630 DEGs and 32 hub genes were found, of which VCAN was an up-regulated DEG, and high expression of VCAN was significantly associated with poor prognosis of ESCC. Moreover, VCAN could also play a role in the immune microenvironment of ESCC, which was mainly manifested by a significant positive correlation between the abundance of VCAN and the abundance of M2 macrophages gene markers, some of which had been reported to be associated with poor prognosis of ESCC. Finally, we also found that VCAN could be regulated by 15 miRNAs in ESCC, some of which had been reported to be associated with ESCC prognosis. ConclusionThis study provides direct and indirect comprehensive evidence for the role of VCAN in ESCC prognosis. The direct evidence is that the survival curve shows that highly expressed VCAN is significantly associated with the poor prognosis of ESCC, and the indirect evidence is that VCAN is positively related to some markers which indicate poor prognosis in the ESCC immune microenvironment, and VCAN can be regulated by some prognostic miRNAs in ESCC.
Objective To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second- line treatment. Conclusion Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.
ObjectiveTo understand the biological behavior of primary squamous cell carcinoma of thyroid (PSCCT), and provide references for its clinical diagnosis and treatment.MethodThe latest domestic and foreign reports of PSCCT were collected and analyzed.ResultsIn the diagnosis of PSCCT, the possibility of metastasis of squamous cell carcinoma to thyroid should be excluded. It often presented with hoarseness, local obstruction, and the median survival time was about 12 months. The treatment mainly relies on complete surgical resection.ConclusionPrimary squamous cell carcinoma of thyroid is a rare disease with rapid disease progression, poor overall prognosis and limited therapeutic options.
Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells （CSCs），which are closely related to tumor initiation，growth，metastasis and chemoresistance. CSCs are also found in esophageal squamous cell carcinoma （ESCC）. These cells are characterized by potential of self-renewal and differentiation，tumor formation in nude mice and chemotherapy resistance，and thus may play an important role in targeted cancer therapies. Current methods for culturing and sorting CSCs in ESCC mainly include fluorescence activated cell sorting （FACS），magnetic activated cell sorting （MACS），suspension culture，and side population （SP） cell sorting. In this review，we focus on current research methods for CSCs in ESCC，their biological characteristics and areas for improvement. We believe that a combination of multiple cell-surface makers is needed for research of CSCs in ESCC.
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.
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.