Transcription Factor E2F4 Promote Proliferation, Migration, and Invasion of Gastric Cancer Cells by transcriptionally activating DSCC1.

Gastric cancer (GC) ranks as the fifth most common cancer and the fourth leading cause of cancer-related deaths globally. Despite advancements in molecular profiling, the mechanisms driving GC proliferation and metastasis remain unclear. This study identifies Early 2 Factor 4 (E2F4) as a key transcription factor that promotes GC cell proliferation, migration, and invasion by upregulating DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) expression. Bioinformatics and transcription factor analyses revealed E2F4 as a significant regulator of DSCC1. Functional assays confirmed E2F4's role in enhancing GC cell malignancy in vitro and in vivo. Knockdown and overexpression experiments demonstrated that E2F4 positively regulates DSCC1 at the transcriptional level, with ChIP-qPCR and dual luciferase reporter assays validating the binding sites on the DSCC1 promoter. These findings highlight the E2F4-DSCC1 axis as a potential therapeutic target to mitigate GC progression.

ACTL8 Promotes the Progression of Gastric Cancer Through PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: Actin-like protein 8 (ACTL8) significantly correlates with tumor growth and prognosis across various cancer types. Nevertheless, the potential relationship between ACTL8 and gastric cancer (GC) remains uncertain. OBJECTIVE: This study aimed to elucidate the role of ACTL8 in human GC cells and to explore its mechanism. METHODS: Bioinformatics analysis tools, such as GEPIA2, Kaplan-Meier, and STRING, were utilized for a comprehensive investigation of the characteristics and functional roles of ACTL8 in GC, including differential expression, prognostic value, and related signaling pathways. Subsequently, gene expression analyses, cell function assays, and signaling pathway experiments were conducted to verify key findings. RESULTS: Bioinformatics analysis showed that ACTL8 was significantly elevated in GC and closely associated with poor prognosis. Gene expression experiments confirmed the bioinformatics results. Furthermore, ACTL8 knockdown markedly reduced GC cell proliferation and inhibited migration and invasion. Mechanistically, a significant increase in the phosphorylation levels of signaling proteins was observed in GC cells following ACTL8 overexpression, and PI3K/Akt/mTOR pathway inhibitors could reverse this effect. CONCLUSION: ACTL8 expression is significantly upregulated in GC cells and is closely correlated with poor patient prognosis. Further mechanistic studies revealed that ACTL8 may promote GC cell migration and proliferation through activation of the PI3K/Akt/mTOR signaling pathway. Consequently, ACTL8 emerges as a promising therapeutic target for GC.

Low ligation of the inferior mesenteric artery in robotic mid-low rectal cancer surgery: a comparative study from a single-center.

Laparoscopic total mesorectal excision is the main surgical approach for treating rectal cancer, but there is still no clear consensus on the issue of low ligation of the inferior mesenteric artery during the procedure. Robotic surgery has been shown to have certain advantages over laparoscopic surgery in multiple studies, but further research is needed to better understand the outcomes of robotic surgery in the context of low ligation procedures. In this study, we included 1590 patients with mid-low rectal cancer. Among them, 942 patients underwent low ligation surgery (LL), divided into 138 in the robotic group and 804 in the laparoscopic group. The high ligation surgery (HL) group consisted of 648 patients. The results of LL vs HL showed that the LL group had faster bowel movement recovery (P = 0.003), lower anastomotic leak rate (P = 0.032), and lower International Prostate Symptom Score (IPSS) at 6 months postoperatively (P < 0.001). The results of Rob-LL vs Lap-LL showed that the Rob-LL group had longer operative time (P < 0.001), less blood loss (P = 0.001), more lymph nodes retrieved (P = 0.045), and lower Wexner score at 2 weeks postoperatively (P = 0.029). The concept of low ligation of the inferior mesenteric artery is a promising surgical approach that can accelerate the patient's functional recovery. When combined with robotic technology, it may offer more benefits than laparoscopic techniques.

The battle within: cell death by phagocytosis in cancer.

The process by which living cells are phagocytosed and digested to death is called cell death by phagocytosis, a term that has just recently been generalized and redefined. It is characterized by the phagocytosis of living cells and the cessation of cell death by phagocytosis. Phagocytosis of dead cells is a widely discussed issue in cancer, cell death by phagocytosis can stimulate phagocytosis and stimulate adaptive immunity in tumors, and at the same time, do not-eat-me signaling is an important site for cancer cells to evade recognition by phagocytes. Therefore, we discuss in this review cell death by phagocytosis occurring in cancer tissues and emphasize the difference between this new concept and the phagocytosis of dead tumor cells. Immediately thereafter, we describe the mechanisms by which cell death by phagocytosis occurs and how tumors escape phagocytosis. Finally, we summarize the potential clinical uses of cell death by phagocytosis in tumor therapy and strive to provide ideas for tumor therapy.

Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2.

Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure DNMT3B expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of PLCG2 methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors in vivo. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.

Identification and experimental verification of a biomarker by combining the unfolded protein response with the immune cells in colon cancer.

BACKGROUND: The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. METHODS: Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. RESULTS: Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. CONCLUSIONS: We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.

Ferroptosis: the balance between death and survival in colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor associated with high morbidity and mortality. Despite an increase in early screening and treatment options, people with CRC still have a poor prognosis and a low 5-year survival rate. Therefore, mining more therapeutic targets and developing means of early diagnosis and determining prognosis are now imperative in the clinical treatment of CRC. Ferroptosis is a recently identified type of regulated cell death (RCD) characterized, which is identified by the accumulation of iron-dependent lipid peroxidation, thereby causing membrane damage and cell death. Recent studies have shown that ferroptosis is associated with tumors, including CRC, and can be involved in CRC progression; however, the underlying mechanisms are complex and heterogeneous and have not been thoroughly summarized. Therefore, this study reviewed the roles of ferroptosis in CRC progression to target ferroptosis-related factors for CRC treatment. The significance of ferroptosis-related biomarkers and genes in the early diagnosis and prognosis of CRC was also investigated. Furthermore, the limitations of ferroptosis studies in the current treatment of CRC, as well as future research perspectives, are discussed.

Comparing the Efficacy of Robotic Versus Laparoscopic Sleeve Gastrectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has emerged as the predominant metabolic bariatric surgery. With a growing number of studies evaluating the feasibility of robotic sleeve gastrectomy (RSG), it becomes imperative to ascertain whether the outcomes of both techniques are comparable. This study endeavors to synthesize existing evidence and juxtapose the surgical outcomes of LSG and RSG. METHODS: We collected articles comparing LSG and RSG published between 2011 and 2024. The compiled data included author names, study duration, sample size, average age, gender distribution, geographical location, preoperative body mass index (BMI), bougie diameter, duration of hospitalization, surgical duration, readmission rates, conversion rates, costs, postoperative percentage of excess weight loss (%EWL), postoperative BMI, mortality rates, and complications. RESULTS: We incorporated 21 articles. Both the RSG and LSG cohorts exhibited comparable rates of readmission, conversion, mortality, and incidence of complications (p > 0.05). Moreover, the efficacy of weight loss was similar between RSG and LSG. Nonetheless, RSG was linked to longer operative duration (WMD, -27.50 minutes; 95% confidence interval [CI], -28.82 to -26.18; p < 0.0001), prolonged hospitalization (WMD, -0.15 days; 95% CI, -0.25 to -0.04; p = 0.006), and elevated expenses (WMD, -5830.9 dollars; 95% CI, -8075.98 to -3585.81; p < 0.0001). CONCLUSIONS: While both RSG and LSG demonstrated positive postoperative clinical outcomes, RSG patients experienced extended hospital stays, longer operative times, and increased hospitalization costs compared to LSG patients. Using the robotic platform for sleeve gastrectomy (SG) in patients with obesity did not appear to offer any clear benefits.

Survival and prognostic factors of primary retroperitoneal sarcomas after surgery: a single-center experience.

PURPOSE: The percentage of retroperitoneal sarcomas (RPS) among all soft tissue sarcomas ranges from 10 to 15%. Surgery remains the gold standard for RPS. In this study, we analyzed the impact of surgical treatment for primary RPS on recurrence and overall mortality at a Chinese institution and identified and evaluated prognostic variables. METHODS: Data from patients with RPS who underwent surgical treatment were retrospectively analyzed. The patients were treated at a single center from January 2000 to June 2018. Retrospectively collected demographic, clinicopathological, and surgical factors were examined. Overall survival (OS) and disease-free survival (DSF) were used as the primary endpoints. Predicted 5-year survival rates, encompassing both DFS and OS, were derived from the Sarculator prognostic nomogram. RESULTS: A total of 110 patients met the inclusion criteria. The median follow-up time after surgery for patients with primary RPS was 5.3 years. During this period, 59 patients died. The 5-year OS and DFS estimates were 63.5% and 35.3%, respectively. In a multivariate analysis, poor OS following surgical treatment of primary RPS was independently correlated with FNCLCC grade (p < 0.001) and surgical margin status (p = 0.016). FNCLCC grade (p = 0.001) and surgical margin status (p = 0.002) were also independently associated with poor DFS. The C-indices for 5-year OS and DFS survival utilizing the Sarculator prognostic nomogram were 0.71 and 0.73 respectively. CONCLUSION: The overall mortality rate of patients with RPS was considered acceptable. OS and DFS prognostic markers were established for primary RPS. Tumor grade and intraregional margins are other factors that affect survival and recurrence.

ZnO nanoparticles encapsulated cellulose-lignin film for antibacterial and biodegradable food packaging.

Foodborne illness caused by consuming foods contaminated by pathogens remains threating to the public health. Despite considerable efforts of using renewable source materials, it is highly demanding to fabricate food packaging with multiple properties including eco-friendliness, bactericidal effect and biocompatibility. Here, sodium lignosulfonate (SL) and ZnO nanoparticles (ZnO NPs) were used as functional filler and structure components, respectively, on the cellulose nanofibers (CNFs)-based films, which endows the produced membrane (CNF/SL-ZnO) the UV-light blocking, antioxidant, and antimicrobial characteristics. Due to the interconnected polymeric structure, the prepared CNF/SL-ZnO films possessed considerable mechanical properties, thermal stability, and good moisture barrier capability. Moreover, the tested samples exhibited an improved shelf life in food packaging. Furthermore, metagenome analysis revealed superior biodegradability of obtained films with negligible side effect on the soil microenvironment. Therefore, the biocompatible, degradable, and antibacterial CNF/SL-ZnO film holds enormous potential for sustainable uses including food packaging.

Retinol Binding Protein 4 Serves as a Potential Tumor Biomarker and Promotes Malignant Behavior in Gastric Cancer.

Background: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown. Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays. Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis. Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.

Comparing cranial-caudal-medial and medial-lateral approaches for laparoscopic right hemicolectomy: a propensity score-matched analysis.

BACKGROUND: The cranial-caudal-medial approach (CCMA) has been proposed for laparoscopic right hemicolectomy nowadays. This study aimed to investigate the safety and oncological efficacy of CCMA in the treatment of right-sided colon cancer compared to the medial-lateral approach (MLA). METHODS: Patients diagnosed with right-sided colon cancer were included from February 2015 to June 2018, retrospectively, dividing into the CCMA group and the MLA group. We compared the basic characteristics and the short-term and long-term outcomes in two groups. RESULTS: Two hundred and ninety-six patients were included in this study. The baseline characteristics were similar in two groups. Compared with MLA group, CCMA group exhibited shorter operation time (136.3 ± 25.3 min vs. 151.6 ± 21.5 min, P < 0.001), lower estimated blood loss (44.1 ± 15.2 ml vs. 51.4 ± 26.9 min, P = 0.010), and more harvested lymph nodes (18.5 ± 7.1 vs. 16.5 ± 5.7, P = 0.021). The 5-year overall survival (OS) rate for the CCMA group was 76.5%, and the 5-year disease-free survival (DFS) rate was 72.3%, both of which were not inferior to the MLA group. No significant difference was found between two groups in terms of other clinical parameters. CONCLUSION: The CCMA in laparoscopic right hemicolectomy is safe and feasible, making the anatomical plane clearer. This approach can shorten the operation time, reduce intraoperative blood loss, harvest more lymph nodes, and yield satisfactory oncological outcomes.

Analysis of Clinical Efficacy and Quality of Life of Braun Anastomosis in Gastrointestinal Reconstruction in Totally Laparoscopic Distal Gastrectomy: A Single-Center Retrospective Study.

OBJECTIVE: This study aimed to compare the clinical efficacy and quality of life of B-IIB (Billroth-II with Braun anastomosis) and B-II (Billroth-II anastomosis) in the alimentary tract reconstruction postoperative totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. METHODS: From February 2016 to January 2022, 158 patients underwent totally laparoscopic distal gastrectomy and D2 lymphadenectomy in Northern Jiangsu People's Hospital, with Billroth-II with Braun anastomosis for 93 patients and Billroth-II anastomosis for 65 patients. The patients' data were collected prospectively and reviewed retrospectively. RESULTS: In this study, the post-op hospital stay of B-IIB group were shorter than B-II group (12.70 ± 3.08 days in the B-IIB group versus 14.12 ± 4.90 days in the B-II group, p < 0.05) and the first post-op flatus time of the B-IIB group were shorter than B-II group (3.49 ± 1.02 days versus 4.08 ± 1.85 days, p < 0.05). Two groups did differ significantly in hemoglobin on postoperative 3 months, albumin at 3 months after operation, and serum sodium on postoperative 3 days and 3 months (p < 0.05), and the B-IIB had an advantage; the complications incidence (Clavien-Dindo grade II or even a higher grade) of the B-IIB group and B-II group were 10.75% and 29.23%, respectively. There being a statistical difference between the two groups. The B-IIB group and the B-II group both had different degrees of weight loss at 3 months after operation compared with preoperative weight. The weight of B-IIB group was 4.04 ± 1.33 kg, which was less than B-II group (8.08 ± 1.47 kg). The difference was statistically significant (p < 0.05). According to the PGSAS (Postgastrectomy Syndrome Assessment Scale), the score of the B-IIB group is lower than that of the B-II group for esophageal reflux gastritis, dyspepsia, and dumping syndrome group (1.84 ± 0.92 VS 2.15 ± 0.85, P = 0.031; 1.86 ± 1.10 VS 2.22 ± 0.91, P = 0.034; 1.98 ± 1.06 VS 2.32 ± 0.94, P = 0.037, respectively). CONCLUSION: Totally laparoscopic distal gastrectomy with Billroth-II Braun reconstruction is a safe and technically feasible method for gastric cancer patients, which can reduce the incidence of postoperative reflux esophagitis and dumping syndrome. Compared with Billroth-II reconstruction, it has advantages in maintaining postoperative nutritional status and electrolyte balance and improving quality of life.

PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

Potential role of the intratumoral microbiota in colorectal cancer immunotherapy.

Colorectal cancer (CRC) has been one of the most common malignancies worldwide. Despite the advances in current therapies, the mortality rate of CRC remains high. Among them, immunotherapy has achieved satisfactory results in some CRC patients, however, how to expand the use of immunotherapy in CRC patients remains an urgent challenge. Surprisingly, the intratumoral microbiota has been found in multiple tumor tissues, including CRC. It has been demonstrated that the intratumoral microbiota is associated with the progression and treatment of CRC, and is able to enhance or decrease anti-tumor immune responses via different mechanisms as well as influence the immunotherapy efficacy, providing new potential therapeutic targets for CRC immunotherapy. In this review, we focus on the characteristics of the intratumoral microbiota, its roles in the genesis and development of CRC, its modulation of anti-tumor immune responses and immunotherapy, and propose potential applications of the intratumoral microbiota in CRC immunotherapy. Additionally, we propose possible directions for future research on the intratumoral microbiota related to CRC immunotherapy.

A nomogram of anastomotic stricture after rectal cancer: a retrospective cohort analysis.

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

Microbes in the tumor microenvironment: New additions to break the tumor immunotherapy dilemma.

Immunotherapies currently used in clinical practice are unsatisfactory in terms of therapeutic response and toxic side effects, and therefore new immunotherapies need to be explored. Intratumoral microbiota (ITM) exists in the tumor environment (TME) and reacts with its components. On the one hand, ITM promotes antigen delivery to tumor cells or provides cross-antigens to promote immune cells to attack tumors. On the other hand, ITM affects the activity of immune cells and stromal cells. We also summarize the dialog pathways by which ITM crosstalks with components within the TME, particularly the interferon pathway. This interaction between ITM and TME provides new ideas for tumor immunotherapy. By analyzing the bidirectional role of ITM in TME and combining it with its experimental and clinical status, we summarized the adjuvant role of ITM in immunotherapy. We explored the potential applications of using ITM as tumor immunotherapy, such as a healthy diet, fecal transplantation, targeted ITM, antibiotics, and probiotics, to provide a new perspective on the use of ITM in tumor immunotherapy.

Robotic versus laparoscopic anterior resection for the treatment of stage II and III sigmoid colon cancer: a propensity score-matched analysis.

Robot-assisted laparoscopic anterior resection is a novel technique. However, evidence in the literature regarding the advantages of robot-assisted laparoscopic surgery (RLS) is insufficient. The aim of this study was to compare the outcomes of RLS versus conventional laparoscopic surgery (CLS) for the treatment of sigmoid colon cancer. We performed a retrospective study at the Northern Jiangsu People's Hospital. Patients diagnosed with sigmoid colon cancer and underwent anterior resection between January 2019 to September 2023 were included in the study. We compared the basic characteristics of the patients and the short-term and long-term outcomes of patients in the two groups. A total of 452 patients were included. Based on propensity score matching, 212 patients (RLS, n = 106; CLS, n = 106) were included. The baseline data in RLS group was comparable to that in CLS group. Compared with CLS group, RLS group exhibited less estimated blood loss (P = 0.015), more harvested lymph nodes (P = 0.005), longer operation time (P < 0.001) and higher total hospitalization costs (P < 0.001). Meanwhile, there were no significant differences in other perioperative or pathologic outcomes between the two groups. For 3-year prognosis, overall survival rates were 92.5% in the RLS group and 90.6% in the CLS group (HR 0.700, 95% CI 0.276-1.774, P = 0.452); disease-free survival rates were 91.5% in the RLS group and 87.7% in the CLS group (HR 0.613, 95% CI 0.262-1.435, P = 0.259). Compared with CLS, RLS for sigmoid colon cancer was found to be associated with a higher number of lymph nodes harvested, similar perioperative outcomes and long-term survival outcomes. High total hospitalization costs of RLS did not translate into better long-term oncology outcomes.

ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis.

Herein, we elucidate the potential role of ANO6 (TMEM16F) in gastrointestinal stromal tumors (GISTs). ANO6 expression in GIST and adjacent normal tissues was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation, apoptosis, and pyroptosis were examined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining, and flow cytometry. In addition, the total iron and Fe2+ levels were assessed. IL-18 and IL-1ß levels were also evaluated. Lipid reactive oxygen species (ROS), cystine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were evaluated using appropriate kits. Ferroptotic markers, including Ptgs2, Chac1, SLC7A11, and SLC3A2, were analyzed by RT-qPCR, western blotting, and immunohistochemistry. ANO6 expression decreased in GIST tissues. ANO6-plasmid inhibits proliferation, induces apoptosis, and promotes pyroptosis in GIST-T1 and GIST-T1 IR cells. The ANO6-plasmid induced ferroptosis, as confirmed by enhanced lipid ROS levels, increased intracellular concentrations of total iron and Fe2+, promoted Ptgs2 and Chac1 expression, reduced Cys, GSH, and GPX4 levels, and downregulated SLC7A11 and SLC3A2 expression after in vitro and in vivo treatment with ANO6-plasmid. Moreover, the ANO6-plasmid inhibited GIST growth in vivo. Therefore, ANO6 may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.