Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology.

Background: Hepatocellular carcinoma (HCC) is a fatal primary malignancy characterized by high invasion and migration. We aimed to explore the underlying metastasis-related mechanism supporting the development of HCC. Methods: The dataset of single cell RNA-seq (GSE149614) were collected for cell clustering by using the Seurat R package, the FindAllMarkers function was used to find the highly expression and defined the cell cluster. The WebGestaltR package was used for the GO and KEGG function analysis of shared genes, the Gene Set Enrichment Analysis (GSVA) was performed by clusterProfiler R package, the hTFtarget database was used to identify the crucial transcription factors (TFs), the Genomics of Drug Sensitivity in Cancer (GDSC) database was used for the drug sensitivity analysis. Finally, the overexpression and trans-well assay was used for gene function analysis. Results: We obtained 9 cell clusters from the scRNA-seq data, including the nature killer (NK)/T cells, Myeloid cells, Hepatocytes, Epithelial cells, Endothelial cells, Plasma B cells, Smooth muscle cells, B cells, Liver bud hepatic cells. Further cell ecological analysis indicated that the Hepatocytes and Endothelial cell cluster were closely related to the cancer metastasis. Subsequently, the NDUFA4L2-Hepatocyte, GTSE1-Hepatocyte, ENTPD1-Endothelial and NDUFA4L2-Endothelial were defined as metastasis-supporting cell clusters, in which the NDUFA4L2-Hepatocyte cells was closely related to angiogenesis, while the NDUFA4L2-Endothelial was related with the inflammatory response and complement response. The overexpression and trans-well assay displayed that NDUFA4L2 exhibited clearly metastasis-promoting role in HCC progression. Conclusion: We identified and defined 4 metastasis-supporting cell clusters by using the single cell technology, the specify shared gene was observed and played crucial role in promoting cancer progression, our findings were expected to provide new insight in control cancer metastasis.

Long non-coding RNAFOXD1-AS1 modulated CTCs epithelial-mesenchymal transition and immune escape in hepatocellular carcinoma in vitro by sponging miR-615-3p.

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.

The Effectiveness and Safety of Open Versus laparoscopic Surgery for Rectal Cancer after Preoperative Chemo-radiotherapy: A Meta-Analysis.

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.

Using Naïve Bayes Algorithm to Estimate the Response to Drug in Lung Cancer Patients.

AIM AND OBJECTIVE: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. RESULT & CONCLUSION: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.