RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy. AIM: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro. METHODS: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis. RESULTS: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of MCTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway. CONCLUSION: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Antígeno B7-H1/genética , Fosfatidilinositol 3-Quinasas/genética , ARN Largo no Codificante/genética , Ratones Desnudos , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción Forkhead/genéticaRESUMEN
BACKGROUND: Only a limited number of studies considered the combined chemo-radiation therapy after surgery for treating locally advanced rectal cancer. Comparative studies on laparoscopic and open procedures indicated that laparoscopy surgery may be associated with fewer postoperative complications. Despite encouraging results from rectal cancer patients who received neoadjuvant chemo-radiotherapy prior to laparoscopic surgery, the acceptance of this procedure remains controversial, and conflicting evidence exists only in the form of retrospective trials. OBJECTIVES: Since laparoscopic surgery was introduced into clinical practice to treat rectal cancer after neoadjuvant chemo-radiotherapy, it has been discussed controversially whether laparoscopic surgery can be performed as effectively as an open procedure. To overcome the biases inherent in any nonrandomized comparison, we analyzed the propensity-matched analysis and randomized clinical trial. In this study, we set out to determine whether laparoscopic resection was non-inferior to open resection in treatment outcomes of rectal cancer after neoadjuvant chemo-radiotherapy. METHODS: Publications on laparoscopic surgery in comparison with open thoracotomy in treatment outcomes of rectal cancer after neo-adjuvant chemo-radiotherapy to November 2017 were collected. Summary hazard ratios (HRs) of endpoints of interest such as 3-OS (overall survival), 3-DFS (disease-free survival), and individual postoperative complications were analyzed in all trials. By using fixed- or random-effects models according to the heterogeneity, meta-analysis Revman 5.3 software was applied to analyze combined pooled HRs. RESULTS: A total of 6 trials met our inclusion criteria. The pooled analysis of 3-DFS showed that laparoscopic surgery did not improve disease -free survival, compared with open thoracotomy (OR =1.48, 95% CI 0.95 - 2.29; P = 0.08), as well with the 3-OS (OR=0.96, 95%CI=0.66-1.41, P=0.084). The pooled result of duration of surgery indicated that laparoscopic surgery had a tendency towards a longer surgery time (SMD= 43.96, 95% CI 34.04- 53.88; P < 0.00001) and a shorter hospital stay (SMD= -0.97, 95% CI -1.75- -0.18; P=0.02). However, no significant differences between laparoscopic surgery and open thoracotomy were observed in terms of the meta-analysis on the number of removed lymph nodes (SMD =-0.37, 95% CI -0.1.77 - 1.03; P = 0.60), blood loss (SMD =-21.30, 95% CI -0.48.36 - 5.77; P = 0.12), positive circumferential resection margin (OR =0.73, 95% CI 0.22- 2.48; P = 0.61) or postoperative complications (OR =0.89, 95% CI 0.67 - 1.17; P = 0.40) l. CONCLUSION: The current data supported the concept that laparoscopic surgery had correlated with a longer operative time but a shorter hospital stay, without superior advantages in short-term survival rates or oncologic efficiency for locally treating advanced rectal cancer after neoadjuvant chemoradiotherapy. However, prospective investigation on long-term oncological results from laparoscopic surgery is required in the future to verify the benefits of laparoscopic surgery over open surgery after chemo-radiation therapy for treating locally advanced rectal cancer.
