Development and validation of a TRIM27-based nomogram for predicting metachronous liver metastasis and prognosis in postoperative colorectal cancer patients.

BACKGROUND: Colorectal cancer ranks among the most prevalent malignancies globally. Accurate prediction of metachronous liver metastasis is crucial for optimizing postoperative management. Tripartite motif-containing protein 27 (TRIM27), an E3 ubiquitin ligase, is implicated in diverse cellular functions and tumorigenesis. METHODS: This study aimed to develop and validate a TRIM27-based nomogram for prognostication in colorectal cancer patients. Transcriptome sequencing of five paired tumor and normal tissue samples identified TRIM27 as a potential prognostic biomarker. Immunohistochemistry was employed to assess TRIM27 expression in colorectal cancer cohorts from two institutions. RESULTS: TRIM27 expression correlated significantly with both the prognosis of colorectal cancer patients and the occurrence of metachronous liver metastasis. A nomogram incorporating TRIM27 and clinical factors was constructed and demonstrated robust predictive accuracy in an independent validation cohort. CONCLUSION: The TRIM27-based nomogram is a valuable prognostic tool for predicting prognosis and metachronous liver metastasis in colorectal cancer patients, aiding in personalized treatment decisions.

Laparoscopic versus open surgery for rectal neuroendocrine tumors: a multicenter real-world study.

BACKGROUND: Owing to the lack of evidence-based medical studies with large sample sizes, the surgical approach for the radical resection of rectal neuroendocrine tumors remains controversial. METHODS: We retrospectively collected the medical records of patients with rectal neuroendocrine tumors who underwent radical resection at 17 large tertiary care hospitals in China between January 1, 2010, and April 30, 2022. All patients were divided into laparoscopic and open surgery groups. After propensity score matching to reduce confounders, the postoperative and oncologic outcomes were compared between the groups. RESULTS: We enrolled 174 patients with rectal neuroendocrine tumors who underwent radical surgery. After random matching, 124 patients were included in the comparison (62, laparoscopic surgery group; 62, open surgery group). The laparoscopic surgery group had fewer complications (14.5% vs. 35.5%, P = 0.007) and superior relapse-free survival (P = 0.048). Subgroup analysis revealed that the laparoscopic surgery group had fewer complications (10.9% vs. 34.7%, P = 0.004), shorter postoperative hospital stays (9.56 ± 5.21 days vs. 12.31 ± 8.61 days, P = 0.049) and superior relapse-free survival (P = 0.025) in the rectal neuroendocrine tumors ≤ 4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was associated with improved postoperative outcomes and oncologic prognosis for patients with rectal neuroendocrine tumors ≤ 4 cm; it can serve as a safe and feasible option for radical surgery of rectal neuroendocrine tumors.

Local Excision Versus Radical Resection for Grade 2 Rectal Neuroendocrine Tumors: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: Studies on grade 2 rectal neuroendocrine tumors are limited, and the optimal treatment for these tumors is not well established. OBJECTIVE: We aimed to compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors. DESIGN: Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the differences between surgery strategies. SETTINGS: Seventeen large-scale Chinese medical centers participated in this study. PATIENTS: A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed. MAIN OUTCOME MEASURES: Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies. RESULTS: A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes on the basis of the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors of ≤1.5-cm size, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups ( p > 0.05). In patients with grade 2 rectal neuroendocrine tumors of >1.5-cm size, relapse-free survival was significantly lower in the local excision group than in the radical resection group ( p = 0.04). LIMITATIONS: The nature of retrospective reviews and a relatively short follow-up period are limitations of this study. CONCLUSIONS: Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors of ≤1.5 cm size without metastasis, whereas radical resection is more beneficial in those of >1.5 cm size. See Video Abstract . ESCISIN LOCAL VERSUS RESECCIN RADICAL PARA TUMORES NEUROENDOCRINOS RECTALES GRADO ANLISIS MULTICNTRICO CON PUNTUACIN DE PROPENSIN COINCIDENTE: ANTECEDENTES:Los estudios sobre los tumores neuroendocrinos rectales de grado 2 son limitados y el tratamiento óptimo para estos tumores no está bien establecido.OBJETIVO:Comparar los resultados oncológicos de la escisión local versus la resección radical para el tratamiento de tumores neuroendocrinos rectales grado 2.DISEÑO:Estudio multicéntrico retrospectivo emparejado por puntuación de propensión para minimizar la heterogeneidad entre grupos y centrarse en la diferencia entre estrategias quirúrgicas.ESCENARIO:Diecisiete centros médicos chinos de gran tamaño participaron en este estudio.PACIENTES:Se analizaron retrospectivamente un total de 144 pacientes con tumores neuroendocrinos rectales grado 2 patológicamente confirmados.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la supervivencia específica del cáncer y la supervivencia libre de recaída para comparar las estrategias quirúrgicas.RESULTADOS:En este estudio se inscribieron un total de 144 pacientes con tumores neuroendocrinos rectales grado 2. Veintisiete pacientes se sometieron a resección endoscópica, 55 a escisión transanal, 50 a resección radical y 12 a cirugía paliativa o biopsia por metástasis a distancia. De los 50 pacientes que se sometieron a resección radical, 30 (60,0%) tenían ganglios linfáticos clínicamente positivos según los resultados histopatológicos. El valor de corte óptimo para el tamaño del tumor para predecir la supervivencia específica del cáncer fue de 1,5 cm. En pacientes con tumores neuroendocrinos rectales grado 2 ≤ 1,5 cm, no hubo diferencias significativas en la supervivencia específica del cáncer y la supervivencia libre de recaída entre los grupos de escisión local y resección radical ( p >0,05). En pacientes con tumores neuroendocrinos rectales grado 2 > 1,5 cm, la supervivencia libre de recaída fue significativamente menor en el grupo de escisión local que en el grupo de resección radical ( p = 0,04).LIMITACIONES:La naturaleza de la revisión retrospectiva y el período de seguimiento relativamente corto son limitaciones de este estudio.CONCLUSIONES:Los tumores neuroendocrinos rectales grado 2 tienen una tasa no despreciable de metástasis en los ganglios linfáticos. La escisión local es una opción factible para tumores ≤ 1,5 cm sin metástasis, mientras que la resección radical es más beneficiosa en aquellos > 1,5 cm. (Traducción-Dr. Felipe Bellolio ).

Long noncoding RNA OVAAL enhances nucleotide synthesis through pyruvate carboxylase to promote 5-fluorouracil resistance in gastric cancer.

5-Fluorouracil (5-FU) is widely used in gastric cancer treatment, yet 5-FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5-FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5-FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP-mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreover, OVAAL knockdown increased sensitivity to 5-FU treatment, which could be reversed by PC overexpression or repletion of oxaloacetate, aspartate, or uridine. OVAAL overexpression enhanced pyrimidine synthesis to promote proliferation and 5-FU resistance of gastric cancer cells, which could be abolished by PC knockdown. Thus, OVAAL promoted gastric cancer cell proliferation and induced 5-FU resistance by enhancing pyrimidine biosynthesis to antagonize 5-FU induced thymidylate synthase dysfunction. Targeting OVAAL-mediated nucleotide metabolic reprograming would be a promising strategy to overcome chemoresistance in gastric cancer.

Laparoscopic versus open selective lateral pelvic lymph node dissection following total mesorectal excision for locally advanced low rectal cancer.

PURPOSES: Lateral pelvic lymph node (LPLN) dissection represents a technically challenging procedure with a high potential risk of surgical morbidity. The purpose of this study was to compare the technical feasibility, safety, and oncological efficacy of laparoscopic LPLN dissection (LPLD) following total mesorectal excision (TME) with open LPLD for locally advanced low rectal cancer (LALRC). METHODS: Between January 2010 and December 2016, consecutive patients with LALRC and swollen LPLNs who underwent laparoscopic or open TME with LPLD at our institution were enrolled in this retrospective observational study. Data regarding patient demographics, perioperative characteristics, and oncological outcomes were analyzed and compared. RESULTS: A total of 64 patients met the inclusion criteria. Thirty-four patients underwent open procedure, and 30 underwent laparoscopic procedure. The mean blood loss volume was significantly less in the laparoscopic group than in the open group (165 vs. 422 mL; P = 0.012). The mean operative time was not significantly different between the laparoscopic and the open groups (354 ± 91 vs. 315 ± 78 min; P = 0.522). The overall postoperative complication rates were 30.0% and 35.3% for the laparoscopic and open groups (P = 0.428), respectively. Postoperative urinary retention was significantly less in the laparoscopic group than in the open group (14.7 vs. 0%; P = 0.036).The duration of postoperative hospital stay was significantly shorter in the laparoscopic group (8.5 ± 3.8 vs. 13.6 ± 6.5 days; P = 0.025). The numbers of harvested lymph nodes and positive resection margin rates showed no significant differences. Pathological LPLN metastases were confirmed in 10 patients (29.4%) in the open group and 11 (36.7%) in the laparoscopic group (P = 0.537). The median follow-up duration was 41.5 months (range 3-98). The laparoscopic and open groups also showed a similar 3-year overall survival rate (88.2% vs. 85.3%; P = 0.577), relapse-free survival rate (73.3% vs. 67.6%; P = 0.889), and local recurrence rate (3.3 vs. 5.9%; P = 0.653). CONCLUSIONS: Laparoscopic TME with LPLD is technically feasible and safe in selected patients with LALRC and is associated with similar oncological outcomes as open approach.

Metformin depresses overactivated Notch1/Hes1 signaling in colorectal cancer patients with type 2 diabetes mellitus.

The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively. The factors involved in Notch1/Hes1 signaling were detected using qRT-PCR and western blot. In our study, we found that lymphatic metastasis, pTNM staging, and the carcinoembryonic antigen level were significantly different between groups. The depth of crypts and the rate of proliferating cell nuclear antigen-positive cells were distinctly higher in DM-CRC and patients who were managed with insulin. Moreover, the goblet cell differentiation rate was decreased in DM-CRC. The expression of Dll1, Notch1, Math1, and RBP-Jκ was increased in DM-CRC, whereas the expression of Dll4 and Hes1 was decreased in this group in normal tissue. In CRC tissue, the expression of Dll1 and Notch1 was clearly higher than that in DM-CRC. Furthermore, the trend in these changes was aggravated with insulin management and alleviated with metformin treatment. In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.

Comparing the antireflux effect of laparoscopic proximal gastrectomy with double-flap technique reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for proximal early gastric cancer: study protocol for a multicentre, prospective, open-label, randomised controlled trial.

INTRODUCTION: Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its feasibility and safety remain uncertain, as only a few retrospective studies have contained postoperative complications and long-term survival data. LPG-DFT for proximal early gastric cancer is still in the early stages of research. Large-scale, prospective randomised controlled trials (RCTs) are necessary to assess the value of LPG-DFT for proximal early gastric cancer. METHODS AND ANALYSIS: This study is a multicentre, prospective, open-label, RCT that investigates the antireflux effect of LPG-DFT compared with laparoscopic total gastrectomy with Roux-en-Y (LTG-RY) reconstruction for proximal early gastric cancer. A total of 216 eligible patients will be randomly assigned to the LPG-DFT group or the LTG-RY group at a 1:1 ratio using a central, dynamic and stratified block randomisation method, if inclusion criteria are met. General and clinical data will be collected when the patient is enrolled in the study and keep pace with the patient at each stage of his medical and follow-up pathway. The primary endpoint is the proportion of patients with reflux esophagitis (Los Angeles Grade B or more) within 12 months postoperatively. The secondary endpoints included intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, postoperative quality of life, postoperative nutrition status, morbidity and mortality rate, and oncological outcomes (3-year overall survival (OS), 3-year disease-free survival (DFS), 5-year DFS and 5-year OS). ETHICS AND DISSEMINATION: The protocol is approved by the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ethics committee (registration number: SYSKY-2022-276-02) on 28 September 2022.We will report the positive as well as negative findings in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05890339.

FMO family may serve as novel marker and potential therapeutic target for the peritoneal metastasis in gastric cancer.

Objective: To explore the relationship between flavin-containing monooxygenases (FMOs) and peritoneal metastasis (PM) in gastric cancer (GC). Materials and methods: TIMER 2.0 was used to perform pan-cancer analysis and assess the correlation between the expression of FMOs and cancers. A dataset from The Cancer Genome Atlas (TCGA) was used to analyze the correlation between FMOs and clinicopathological features of GC. PM is well established as the most common mode of metastasis in GC. To further analyze the correlation between FMOs and PM of GC, a dataset was obtained from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database. The results were validated by immunohistochemistry. The relationship between FMOs and PM of GC was explored, and a novel PM risk signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. The regression model's validity was tested by multisampling. A nomogram was established based on the model for predicting PM in GC patients. The mechanism of FMOs in GC patients presenting with PM was assessed by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses in TCGA and GEO datasets. Finally, the potential relationship between FMOs and immunotherapy was analyzed. Results: The pan-cancer analysis in TCGA and GEO datasets showed that FMO1 was upregulated, while FMO2 and FMO4 were downregulated in GC. Moreover, FMO1 and FMO2 correlated positively with the T and N stage of GC in the TCGA dataset. FMO1 and FMO2 expression was a risk factor for GC (hazard ratio: 1.112 and 1.185). The overexpression of FMO1 was significantly correlated with worse disease-free-survival (DFS) and overall survival (OS). However, no relationship was found between FMO2 expression in GC and DFS and OS. PM was highly prevalent among GC patients and typically associated with a worse prognosis. FMO1 was highly expressed in GC with PM. FMO1 and FMO2 were positively correlated with PM in GC. We identified a 12-gene panel for predicting the PM risk signature by LASSO (Area Under Curve (AUC) = 0.948, 95%CI: 0.896-1.000). A 10-gene panel for PM prediction was identified (AUC = 0.932, 95%CI: 0.874-0.990), comprising FMO1 and FMO2. To establish a model for clinical application, a 7-gene panel was established (AUC = 0.927, 95% CI: 0.877-0.977) and successfully validated by multisampling. (AUC = 0.892, 95% CI: 0.878-0.906). GO and KEGG analyses suggest that FMO1 and FMO2 regulate the extracellular matrix and cell adhesion. FMO1 and FMO2 were positively correlated with the immune score of GC, and their expression was associated with the infiltration of immune cells. Conclusion: PM in GC is strongly correlated with FMOs. Overall, FMO1 and FMO2 have huge prospects for application as novel diagnostic and therapeutic targets.

Marine fungus-derived alkaloid inhibits the growth and metastasis of gastric cancer via targeting mTORC1 signaling pathway.

Gastric cancer (GC) is a highly aggressive and deadly disease worldwide. Given the limitations of current treatments, it is crucial to discover more effective antitumor drugs. Here, we demonstrated that arthpyrone M (Art-M), a novel 4-hydroxy-2-pyridone alkaloid derived from the marine fungus Arthrinium arundinis, inhibited the proliferation, invasion and migration of GC both in vivo and in vitro. The underlying mechanism of Art-M in GC cells was explored by RNA-sequencing analysis, qRT-PCR and immunoblotting, which demonstrated that Art-M significantly suppressed the mTORC1 pathway by decreasing phosphorylated mTOR and p70S6K. Moreover, Art-M feedback increased the activities of AKT and ERK. Co-immunoprecipitation and immunoblotting analysis revealed that Art-M induced dissociation of Raptor from mTOR and promoted Raptor degradation, leading to the inhibition of mTORC1 activity. Art-M was identified as a novel and potent mTORC1 antagonist. Furthermore, Art-M enhanced GC cell sensitivity to apatinib, and the combination of Art-M and apatinib showed better efficacy in the treatment of GC. Taken together, these results demonstrate that Art-M is a promising candidate drug for the treatment of GC by suppressing the mTORC1 pathway.

Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer.

BACKGROUND: Gastric cancer is a prevalent cause of tumor death. Tumor immunotherapy aims to reshape the specific immunity to tumors in order to kill the tumor. LncRNAs play a pivotal role in regulating the tumor immune microenvironment. Herein, immune-related lncRNAs were used to establish a prognosis risk-assessment model for gastric cancer and provide personalized predictions while providing insights and targets for gastric cancer treatment to enhance patient prognosis. METHODS: Gastric adenocarcinoma transcriptome and clinical data were acquired from the The Cancer Genome Atlas (TCGA) database to screen the immune-related lncRNAs. Then, LASSO COX regression was utilized to construct the prognosis risk-assessment model. Afterward, the reliability of the model was evaluated the relationship between immune infiltration, clinical characteristics, and the model was analyzed. RESULTS: We identified 13 lncRNAs and constructed the prognosis assessment model. According to the median risk score of the training set, the patients were assigned to different risk groups. Overall survival time was shorter in the high-risk group. In the high-risk group, higher infiltration of mono-macrophages, dendritic cells, CD4+ T cells, and CD8+ T cells was observed. Moreover, the model was positively related to tumor metastasis. CONCLUSION: The prognosis risk-assessment model developed in this research can effectively predict the prognosis of gastric cancer patients. This tool is expected to be further applied to clinics in the future, thus providing a novel target for immunotherapy in gastric cancer patients.

A novel prognostic signature based on cuproptosis-related lncRNA mining in colorectal cancer.

Background: Colorectal cancer (CRC) is a common malignant tumor that affects the large bowel or the rectum. Cuproptosis, recently discovered programmed cell death process, may play an important role in CRC tumorigenesis. Long non-coding RNAs (lncRNAs) can alter the proliferation of colorectal cancer cells through the control and activation of gene expression. To date, cuproptosis-related lncRNAs, have not been investigated as potential predictive biomarkers in colorectal cancer. Methods: The mRNA and lncRNA expression data of colorectal cancer were gathered from The Tumor Genome Atlas (TCGA) database, and Pearson correlation analysis and univariate Cox regression analysis were used to identify the lncRNAs with differential prognosis. Colorectal cancer was classified using consistent clustering, and the clinical significance of different types, tumor heterogeneity, and immune microenvironment differences was investigated. The differential lncRNAs were further screened using LASSO regression to develop a risk scoring model, which was then paired with clinicopathological variables to create a nomogram. Finally, the copy number changes in the high-risk and low-risk groups were compared. Results: Two clusters were formed based on the 28 prognostic cuproptosis-related lncRNAs, and the prognosis of cluster 2 was found to be significantly lower than that of cluster 1. Cluster 1 showed increased immune cell infiltration and immunological score, as well as strong enrichment of immune checkpoint genes. Next, LASSO regression was used to select 11 distinctive lncRNAs, and a risk score model was constructed using the training set to distinguish between high and low-risk groups. Patients in the high-risk group had a lower survival rate than those in the low-risk group, and both the test set and the total set produced consistent results. The AUC value of the ROC curve revealed the scoring model's efficacy in predicting long-term OS in patients. Moreover, the model could be used as an independent predictor when combined with a multivariate analysis of clinicopathological features, and our nomogram could be used intuitively to predict prognosis. Conclusion: Collectively, we developed a risk model using 11 differential lncRNAs and demonstrated that the model has predictive value as well as clinical and therapeutic implications for predicting prognosis in CRC patients.

Three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: better promote postoperative sexual and urinary function of a propensity-matched study.

Laparoscopic total mesorectal excision (TME) with autonomic nerve preservation (ANP) is a common procedure for rectal cancer (RC), associated with a high prevalence of postoperative urogenital and anorectal dysfunctions. Compared to 2D laparoscopy, 3D laparoscopy provides better depth perception of the surgical field and hand-eye coordination to achieve better outcomes. We compared the performance of 2D and 3D laparoscopy on preserving urogenital and anorectal function in TME+ANP surgery for rectal cancer using propensity-score matching. Data were collected from consecutive male patients who underwent 3D or 2D laparoscopic TME+ANP for primary RC at our institution between March 2012 and December 2020. The primary outcome was sexual and urinary function 1 year after surgery. A total of 450 male patients were eligible. After 1:1 matching, 146 cases were included in each group for analysis. One year after surgery, the prevalence of sexual dysfunction (International Index of Erectile Function score <26) was 8.22% in the 3D laparoscopic group and 44.52% in the 2D laparoscopic group, respectively (P=0.000) and a significant difference in the incidence of urinary retention was observed (n=3 and 24, respectively (P=0.000)). Moreover, blood loss, operative time, duration of hospital stay, and the time to first flatus in the 3D laparoscopic group were significantly less than in the 2D laparoscopic group. In conclusion, 3D laparoscopic TME is associated with lower incidences of postoperative sexual and urinary dysfunction than 2D laparoscopic TME for rectal cancer in male patients.

LncRNA LINC01537 Promotes Gastric Cancer Metastasis and Tumorigenesis by Stabilizing RIPK4 to Activate NF-κB Signaling.

Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.

Targeting autophagy peptidase ATG4B with a novel natural product inhibitor Azalomycin F4a for advanced gastric cancer.

Advanced gastric cancer (GCa) remains highly lethal due to the lack of effective therapies. Identifying promising therapeutic targets and developing effective treatment against GCa are urgently needed. Through mRNA and protein analysis of GCa clinical tumor samples, we found that autophagy-related gene 4B (ATG4B) was overexpressed in GCa tumors and that its high expression was associated with patients' poor prognosis. Knockdown of ATG4B significantly inhibited GCa cell survival and tumor growth. To further probe the role of ATG4B in GCa by pharmacological means, we screened an in-house marine natural compound library against ATG4B and identified Azalomycin F4a (Am-F4a) as a novel and potent ATG4B inhibitor. Am-F4a directly bound to ATG4B with high affinity and effectively suppressed GCa cell autophagy via inhibition of ATG4B both in vitro and in vivo. Moreover, Am-F4a or ATG4B knockdown significantly suppressed tumor growth as well as GCa cell migration and invasion. Am-F4a effectively blocked the metastatic progression of primary GCa and sensitized tumors to chemotherapy. Taken together, our findings indicate that ATG4B is a potential therapeutic target against GCa and the natural product Am-F4a is a novel ATG4B inhibitor that can be further developed for the treatment of GCa.

Magnetic resonance neuroimaging promotes the preservation of pelvic autonomic nerves in laparoscopic total mesorectal excision: a comparative study.

BACKGROUND: How to preserve pelvic autonomic nerves system (PANS) in total mesorectal excision (TME) is still a technical challenge for gastrointestinal surgeons, and nerve preservation according to preoperative magnetic resonance imaging (MRI) is a hot topic in pelvic surgery. The purpose of this study was to assess the postoperative urogenital function of patients with rectal cancer (RC) who underwent preoperative and postoperative neuroimaging of PANS vs. patients who did not. METHODS: Patients meeting the inclusion criteria were prospectively enrolled in a magnetic resonance neuroimaging (MRN) group from June 2018, while primary RC patients from January 2016 to May 2018 who met the inclusion criteria were enrolled in a non-MRN group. Patients in the MRN group underwent MRN examination before operation and 6 months after operation, while those in the non-MRN group were collected and analyzed retrospectively. RESULTS: Based on International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5 (IIEF5) scores at 6 months, the postoperative urinary and sexual function of male patients in the MRN group were significantly better than that in the non-MRN group (P<0.05). In addition, based on International Consultation on Incontinence modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Female Sexual Function Index (FSFI) scores at 6 months, the postoperative sexual function of female patients in the MRN group was significantly better than that in the non-MRN group (P<0.05). CONCLUSIONS: In the present study, we constructed a three-dimensional (3D) presentation of PANS based on preoperative MRN which showed in vivo pelvic autonomous innervation. This may promote the preservation of PANS during TME and reduce the postoperative urogenital dysfunction rate.

Tumor deposit indicates worse prognosis than metastatic lymph node in gastric cancer: a propensity score matching study.

BACKGROUND: The prognostic value of tumor deposit (TD) in gastric cancer is controversial. This study aims to investigate the prognostic value of TD. METHODS: The consecutive patients diagnosed with gastric cancer from October 2007 to October 2012 were selected. The patients were divided by whether they suffered TD into two groups. The basic data were comparable between the two groups after propensity score matching (PSM), then survival analysis [overall survival (OS) and cancer-specific survival (CSS)] was applied in two groups. After that, all the patients were divided by pN staging and survival analysis were applied in each subgroup. At last, all patients were divided into TD group, pN1 stage group, pN2 stage group, pN3a, and pN3b stage group, OS and CSS were compared between them. Multivariable competing risk analyses tested association of TD with OS and CSS, before and after PSM. RESULTS: Eight hundred and three patients were concluded. After PSM, 137 patients with TD and 274 patients without TD were selected, the 5-year OS and CSS rates of patients with TD were significantly worse than patients without TD (OS: 19.7% vs. 42.0%, P<0.001; CSS: 22.6% vs. 45.6%, P<0.001). In all patients' survival analysis, the 5-year OS and CSS rates of TD group were comparable with pN3a group (OS: 19.7% vs. 25.3%, P=0.221, CSS: 22.6% vs. 30.1%, P=0.092) and pN3b group (OS: 19.7% vs. 19.6% P=0.349, CSS: 22.6% vs. 23.5%, P=0.452). Meanwhile, on multivariable cox regression analyses, the presence of TD significantly reduces the OS and CSS of patients in gastric cancer. CONCLUSIONS: TD has a marked impact on the prognosis of gastric cancer. Even patients with TD had the same prognosis with pN3 stage.

Long Non-Coding RNA STARD13-AS Suppresses Cell Proliferation And Metastasis In Colorectal Cancer.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. METHODS: The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, flow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. RESULTS: Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. CONCLUSION: Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.

A Comparison of Outcomes between Lichtenstein and Laparoscopic Transabdominal Preperitoneal Hernioplasty for Recurrent Inguinal Hernia.

There remain concerns about the optimal technique for repairing recurrent inguinal hernias because of the high risks of complications and recurrence. The aim of this study was to compare Lichtenstein hernioplasty with the transabdominal preperitoneal (TAPP) laparoscopic technique in the treatment of recurrent inguinal hernias. One hundred twenty-two patients who underwent surgery for recurrent inguinal hernia were prospectively randomized to receive either Lichtenstein (n = 63) or TAPP (n = 59) hernioplasty between January 2010 and December 2014. Baseline characteristics, intraoperative complications, and short- and long-term postoperative factors were evaluated. Preoperative factors were comparable between the two groups. The average follow-up period was 46.2 ± 8.5 months. The two groups had similar intraoperative and short-term postoperative complication rates, whereas the rate of long-term postoperative complications was lower for the TAPP group than the Lichtenstein group (6.8% vs 23.8%, respectively, P = 0.012). The TAPP group had significantly lower visual analogue scale scores, fewer analgesics consumption, and faster recovery than the Lichtenstein group (P < 0.05). Chronic pain was more prevalent in the Lichtenstein group than the TAPP group (15.9% vs 3.4%, respectively, P = 0.031). The recurrence rate was 4.8 per cent for the Lichtenstein group and 1.7 per cent for the TAPP group, with no significant difference (P = 0.62). Both the Lichtenstein and TAPP procedures are safe and effective methods for repairing recurrent inguinal hernia with low incidence rates of life-threatening complications and recurrence. The TAPP procedure is superior to the Lichtenstein repair in terms of reduced postoperative pain, shorter sick leave, faster recovery, and better cosmetic results. Careful selection of the surgical procedures and implementation of technical essentials are necessary.

Vascularizing lymph node dissection for advanced gastric cancer: A single-institution experience.

AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution. METHODS: Data of 315 patients with advanced gastric cancer who underwent standard D2 lymphadenectomy with curative intent was collected between January 1994 and December 2006. One hundred and fifty-two patients received VLND while 163 patients received NVLND. Short- and long-term clinical outcomes were compared between the two groups. RESULTS: The median followed-up time was 82 mo. The rate of postoperative complications in the VLND group was 13.2%, while that in the NVLND group was 11.7% (P = 0.686). The overall 5-year survival rate was 64% in the VLND group and 59% in the NVLND group (P = 0.047). When subgroup analyses were performed according to Bormann type, type of differentiation and lymph node status, survival benefit was demonstrated in patients with Bormann type III or IV (59% vs 50%, P = 0.032), undifferentiated type (63% vs 49%, P = 0.021) or presence of lymph node metastasis (53% vs 38%, P = 0.010) in the VLND group. CONCLUSION: D2 VLND in advanced gastric cancer treatment allows survival benefit with acceptable morbidity and mortality. VLND for patients with potentially curable advanced gastric cancer is feasible and safe when performed by a well-trained surgical team.