摘要
【Objective】 To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods. 【Methods】 ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas (TCGA), R software was employed to detect the differential expression mRNAs, and related clinical information was collected for survival analysis. To validate the bioinformatics results, Real-time quantitative PCR (qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues. Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features. The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR. 【Results】 Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis. Clinical specimens were detected, the expressions of ARL5B mRNA and protein were the highest in metastases lymph node, followed by esophageal cancer tissues and adjacent tissues, which corresponded with bioinformatics results. The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage. Kaplan-Meier analysis results denoted high ARL5B level, indicating poor prognosis. Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport, late endosome to lysosome transport, and organelle localization. Protein-protein interaction analysis (PPI) suggested that ARL5B might interact with VPS16, KIF1A and TOM1, whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression. 【Conclusion】 ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases, advanced clinical stage, and poor prognosis. ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms.
摘要
Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.
摘要
Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.
摘要
Objective:To evaluate the efficacy and prognostic factors of radiotherapy combined with immunotherapy as the first-line treatment for patients with locally advanced or metastatic esophageal squamous cell carcinoma (LA/M ESCC).Methods:A single-center, retrospective analysis was conducted for the recent efficacy, survival, prognostic factors, post-treatment failure modes, and treatment-related adverse reactions of 57 LA/M ESCC patients eligible for enrollment.Results:The entire group of patients had 1-, 2-, and 3-year overall survival (OS) of 86.0%, 57.5%, and 53.9%, respectively and 1-, 2-, and 3-year progression-free survival (PFS) of 61.4%, 31.0%, and 31.0%, respectively. The median OS was not reached, and the median PFS was 15.0 (95% CI: 10.77-19.23) months. These patients had an overall response rate (ORR) of 80.7% (46/57) and a disease control rate (DCR) of 94.7% (54/57). As indicated by the result of the multivariate analysis, the independent prognostic factors affecting the OS of the patients included their age, clinical stage, number of immunotherapy cycles, and recent efficacy ( HR = 0.25, 2.58, 0.35, 4.05, P < 0.05), and the independent factors influencing the PFS of the patients included their clinical stage and recent efficacy ( HR = 2.27, 1.97, P < 0.05). There were no statistically significant differences in the effects of irradiation ranges and the combination modes of immunologic drugs and chemoradiotherapy on both OS and PFS of the patients ( P > 0.05). A total of 32 patients suffered post-treatment failure. After the second treatment, they had 1- and 2-year OS of 55.7% and 25.3%, respectively, with median OS of 14.0 (95% CI: 5.17-22.83) months. A total of 26 cases experienced treatment-associated adverse reactions of grades 2 or higher during and after treatment. Conclusions:The combination of radiotherapy and immunotherapy is effective and safe as the first-line treatment for LA/M ESCC patients. The post-treatment failure modes still include local recurrence and distant metastasis. Therefore, such combination merits further investigation.