The potential for tumor occurrence triggered by cancer stem cells (CSCs) has emerged as a significant challenge for human colorectal cancer therapy. However, the underlying mechanism of CSC development remains controversial. Our study provided evidence that the bulk of tumor cells could dedifferentiate to CSCs and reacquire CSC‐like phenotypes if cultured in the presence of extracellular matrix reagents, such as Matrigel and fibrin gels. In these 3D gels, CD133− colorectal cancer cells can regain tumorigenic potential and stem‐like phenotypes. Mechanistically, the 3D extracellular matrix could mediate cytoskeletal F‐actin bundling through biomechanical force associated receptors integrin β1 (ITGB1), contributing to the release of E3 ligase tripartite motif protein 11 (TRIM11) from cytoskeleton and degradation of the glycolytic rate‐limiting enzyme phosphofructokinase (PFK). Consequently, PFK inhibition resulted in enhanced glycolysis and upregulation of hypoxia‐inducible factor 1 (HIF1α), thereby promoting the reprogramming of stem cell transcription factors and facilitating tumor progression in patients. This study provided novel insights into the role of the extracellular matrix in the regulation of CSC dedifferentiation in a cytoskeleton/glycolysis‐dependent manner.
Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.
To compare and analyze the differences in safety, feasibility and short-term e cacy between robotassisted and totally robotic surgery in Right Hemicolectomy. MethodsA retrospective analysis was conducted on the clinical data of 184 patients who underwent right hemicolectomy in The Second Xiangya Hospital of Central South University from July 2016 to December 2021. 148 patients were matched (including 74 cases of robot-assisted right hemicolectomy (TRAH) and 74 cases of totally robotic right hemicolectomy (TRRH)). The general information, surgical and pathological results and complications of patients were collected and analyzed. ResultsThe incision length was 5.14 ± 0.60cm in the robot-assisted group 4.74 ± 0.55cm in the totally robotic group (p < 0.001). The blood loss was 86.28 ± 52.57 ml in the robot-assisted group and 69.19 ± 44.78 ml in the totally robotic group (p = 0.035).The operative time of the robot-assisted group was 197.50 (171.25, 242.25) min, and that of the totally robotic group was 160.00 (145.00, 188.75) min (p < 0.001).The postoperative hospital stay was 11.18 ± 4.32 days in the robot-assisted group and 9.53 ± 4.42 days in the totally robotic group (p = 0.023). NRS pain scores were 3.05 ± 0.23 for the robot-assisted group and 2.96 ± 0.26 for the totally robotic group (p = 0.019). The extraction time of abdominal drainage was 7.54 ± 1.44 days in the robot-assisted group and 7.00 ± 1.25 days in the totally robotic group (p = 0.016).postoperative complications in the robot-assisted group were as follows: Urinary retention 1 (1.4%), chylous stula 1 (1.4%), wound complications 3 (4.1%), postoperative intestinal obstruction 1 (1.4%), postoperative anastomosis 3 (4.1%), other complications 4 (5.4%);postoperative complications in the totally robotic group included 0 cases of urinary retention, 7 cases of chylous stula (9.3%), 1 case of wound complication (1.3%), 0 cases of postoperative intestinal obstruction, 2 cases of postoperative anastomotic complications (2.7%), and 0 cases of other complications. ConclusionsComplete robotic right hemicolectomy in the hands of an experienced colorectal surgeon is safe and feasible. Compared with robot-assisted right hemicolectomy, the totally robotic right hemicolectomy group has certain advantages in incision length, operative time, intraoperative blood loss, postoperative hospital stay, rst exhaust time, rst liquid diet time, Time of drainage tube removal, NRS pain score and postoperative complications. SynopsisTo compare and analyze the differences in safety, feasibility and short-term e cacy between robotassisted and totally robotic surgery in Right Hemicolectomy. A retrospective analysis was conducted on the clinical data of 184 patients who underwent right hemicolectomy.148 patients were matched (including 74 cases of robot-assisted right hemicolectomy (TRAH) and 74 cases of totally robotic right hemicolectomy (TRRH)). We found that compared with robot-assisted right hemicolectomy, the totally robotic right hemicolectomy group has certain advantages in in...
Objective To compare and analyze the differences in safety, feasibility and short-term efficacy between robot-assisted and totally robotic surgery in Right Hemicolectomy. Methods A retrospective analysis was conducted on the clinical data of 184 patients who underwent right hemicolectomy in The Second Xiangya Hospital of Central South University from July 2016 to December 2021. 148 patients were matched (including 74 cases of robot-assisted right hemicolectomy (TRAH) and 74 cases of totally robotic right hemicolectomy (TRRH)). The general information, surgical and pathological results and complications of patients were collected and analyzed. Results The incision length was 5.14 ± 0.60cm in the robot-assisted group 4.74 ± 0.55cm in the totally robotic group (p < 0.001). The blood loss was 86.28 ± 52.57 ml in the robot-assisted group and 69.19 ± 44.78 ml in the totally robotic group (p = 0.035).The operative time of the robot-assisted group was 197.50 (171.25, 242.25) min, and that of the totally robotic group was 160.00 (145.00, 188.75) min (p < 0.001).The postoperative hospital stay was 11.18 ± 4.32 days in the robot-assisted group and 9.53 ± 4.42 days in the totally robotic group (p = 0.023). NRS pain scores were 3.05 ± 0.23 for the robot-assisted group and 2.96 ± 0.26 for the totally robotic group (p = 0.019). The extraction time of abdominal drainage was 7.54 ± 1.44 days in the robot-assisted group and 7.00 ± 1.25 days in the totally robotic group (p = 0.016). postoperative complications in the robot-assisted group were as follows: Urinary retention 1 (1.4%), chylous fistula 1 (1.4%), wound complications 3 (4.1%), postoperative intestinal obstruction 1 (1.4%), postoperative anastomosis 3 (4.1%), other complications 4 (5.4%);postoperative complications in the totally robotic group included 0 cases of urinary retention, 7 cases of chylous fistula (9.3%), 1 case of wound complication (1.3%), 0 cases of postoperative intestinal obstruction, 2 cases of postoperative anastomotic complications (2.7%), and 0 cases of other complications. Conclusions Complete robotic right hemicolectomy in the hands of an experienced colorectal surgeon is safe and feasible. Compared with robot-assisted right hemicolectomy, the totally robotic right hemicolectomy group has certain advantages in incision length, operative time, intraoperative blood loss, postoperative hospital stay, first exhaust time, first liquid diet time, Time of drainage tube removal, NRS pain score and postoperative complications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.