lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

Preoperative T-staging of Colorectal Cancer by Dual-energy Computed Tomography: A Retrospective Study.

BACKGROUND: Preoperative T-staging is essential for planning optimal treatment and care for colorectal cancer (CRC). OBJECTIVE: To evaluate the accuracy of Dual-energy CT (DECT) in preoperative T-staging of CRC. METHODS: The clinical data and DECT images of 37 patients with 39 CRC lesions were retrospectively analyzed. The performance of the DECT quantitative parameters in CRC T-staging was evaluated. Postoperative pathologic results were used as a gold standard. Receiver operating characteristic curves were used to assess the diagnostic efficacy of DECT parameters. P < 0.05 was deemed significant. RESULTS: The overall accuracy of T-staging by DECT was 76.9%. The DECT parameters were significantly different between the T3 pericolic fat stranding, T4a pericolic fat stranding, and normal pericolic fat stranding. Arterial phase λHU had the best diagnostic performance with a cut-off value of ≥0.967, resulting in a 70.6% sensitivity and a 100% specificity in differentiating between T3 and T4a stages of CRC. CONCLUSION: DECT has high accuracy in the T-staging of CRC. Arterial phase λHU has the best diagnostic performance in differentiating between T3 and T4a stages of CRC.

Preoperative prognostic nutritional index associated with anastomotic leakage in colorectal cancer patients after surgery.

BACKGROUND: Anastomotic leakage (AL) is a severe complication of colorectal cancer (CRC) surgery and is associated with the immune and nutritional status. OBJECTIVES: This study aimed to investigate the role of the prognostic nutritional index (PNI) in AL in CRC patients after surgery. MATERIAL AND METHODS: A retrospective case-control study was designed in a single center. The clinicopathological features and preoperative laboratory data of 124 CRC patients and 120 non-cancer patients who underwent surgery were collected and examined. Among the CRC patients, 24 had AL. RESULTS: Nutritional indicators were lower in CRC patients than in non-cancer patients (p < 0.05), but the clinical parameters analysis showed that only metastasis (M) stage, albumin, carcinoembryonic antigen (CEA), CA153, and PNI were associated with AL in CRC after surgery (p < 0.05). Prognostic nutritional index had a moderate predictive value for AL, with an area under the curve (AUC) of 0.625. Using the median value as a cutoff point, a high PNI was associated with a longer survival time in CRC patients (p = 0.033), and AL showed marginal significance (p = 0.048). The nomogram showed that PNI has a better prognostic value than tumor-node-metastasis (TNM) staging in CRC patients who underwent surgery. CONCLUSIONS: Prognostic nutritional index is a useful supplement for predicting AL in CRC patients after colorectal surgery. It also helps predict the prognosis of CRC patients.

Systematic analyzing a five- miRNA panel and its diagnostic value of plasma expression in colorectal cancer.

BACKGROUND: Aberrant expression of miRNAs have been implicated in cancers, but the role of miRNAs in colorectal cancer (CRC) remains need to be elucidated. This study aimed to identify miRNAs that related to colorectal cancer (CRC) pathogenesis and determine the diagnostic value. METHODS: Three GEO datasets (GSE128449, GSE35602 and GSE49246) with 131 samples were used to screen miRNAs that differential expression between tumor and control tissues. The expression of the identified miRNAs was validated in 50 clinical tissue samples and the GSE35834 dataset. The clinical significance of these miRNAs was analyzed in the TCGA dataset and clinical tissue samples. The expression of miRNAs in tissues and plasma samples were tested by RT-PCR assay in clinical samples, and their diagnostic value was determined. RESULTS: The analysis of three GEO datasets revealed that miR-595 and miR-1237 were upregulated, while miR-126, miR-139, and miR-143 were downregulated in CRC tissues compared to control tissues. The differential expression of the five miRNAs in CRC tissues was confirmed using clinical tissue samples and GEO databases. There was no significant correlation between the TNM stage and tumor stage of CRC and any of the five miRNAs. Plasma expression of the miRNAs differed significantly between CRC and non-cancer patients, and each miRNA had moderate diagnostic value for CRC. Combining the five miRNAs provided better diagnostic potential for CRC than a single miRNA. CONCLUSIONS: This study demonstrated that five miRNAs were related to the pathogenesis of CRC, but independent of the stage of CRC; Plasma expression of these miRNAs have moderate diagnostic value, and combination of these miRNAs showed better diagnostic ability in CRC.

Comprehensive investigation of the prognostic values and molecular mechanisms of syntaxin binding protein 5 antisense RNA 1 in patients with colon adenocarcinoma based on RNA sequencing dataset.

Objective: The main purpose of this study is to perform a comprehensive investigation of the prognostic value and molecular mechanism of syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1) through the whole genome RNA sequencing data of the The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort. Methods: There were 438 COAD patients were fit into current study for survival analysis. Gene expression profiling interactive analysis 2.0, Database for Annotation, Visualization and Integrated Discovery v6.8, gene set enrichment analysis (GSEA) and connectivity map (CMap) are used to investigate the molecular mechanisms and targeted drugs of STXBP5-AS1 in COAD. Results: By comparing the expression level of tumor and non-tumor tissues, we found that STXBP5-AS1 was notablely down-regulated in COAD tumor tissues. Survival analysis suggested that low STXBP5-AS1 expression was significantly related to poor overall survival (OS) of COAD (log-rank P=0.035, adjusted P=0.005, HR=0.545, 95%CI=0.356-0.836). The enrichment analysis of STXBP5-AS1 co-expressed genes, GSEA and differentially expressed genes suggests that STXBP5-AS1 may play a part in COAD by regulating the following biological processes or pathways: cell junction, DNA replication, apoptosis, cell cycle, metastasis, tumor protein 53, Wnt, mTORC1, MCM, notch receptor 4, transforming growth factor beta receptor, and cGMP-PKG signaling pathway. CMap analysis was screened out four small molecule drugs (anisomycin, cephaeline, NU-1025 and quipazine) that may be used as STXBP5-AS1 targeted therapy drugs in COAD. The co-expression analysis of STXBP5-AS1 and immune cell gene signature indicated that STXBP5-AS1 was significantly related to immune cell gene set in normal intestinal tissues, but not in COAD tumor tissues. Conclusion: Our results revealed that STXBP5-AS1 is notablely down-regulated in COAD tumor tissues, and may act as a novel prognostic biomarker for COAD.

Prophylactic abdominal drainage following appendectomy for complicated appendicitis: A meta-analysis.

Background: To date, the value of prophylactic abdominal drainage (AD) following appendectomy in patients with complicated appendicitis (CA), including adults and children, has yet to be determined. This paper presents a meta-analysis of the effects of prophylactic AD on postoperative complications in patients with CA, with the goal of exploring the safety and effectiveness of prophylactic AD. Methods: PubMed, Science Direct, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published before August 1, 2022. The primary outcomes were the complication rates [overall incidence of postoperative complications, incidence of intra-abdominal abscess (IAA), wound infection (WI), and postoperative ileus (PI), and the secondary outcome was the perioperative outcome]. The meta-analysis was performed with STATA V. 16.0A. Results: A total of 2,627 articles were retrieved and 15 high-quality articles were eventually included after screening, resulting in a total of 5,123 patients, of whom 1,796 received AD and 3,327 did not. The results of this meta-analysis showed that compared with patients in the non-drainage group, patients in the drainage group had longer postoperative length of hospitalization (LOH) (SMD = 0.68, 95% CI: 0.01-1.35, P = 0.046), higher overall incidence of postoperative complications (OR = 0.50, 95% CI: 0.19-0.81, P = 0.01), higher incidence of WI (OR = 0.30, 95% CI: 0.08-0.51, P = 0.01) and PI (OR = 1.05, 95% CI: 0.57-1.54, P = 0.01), the differences were statistically significant. However, there was no significant difference in the incidence of IAA (OR = 0.10, 95% CI: -0.10 to 0.31, P = 0.31) between the two groups. The results of subgroup meta-analysis showed that in the adult subgroup, the overall incidence of postoperative complications in the drainage group was higher than that in the non-drainage group (OR = 0.67, 95% CI: 0.37-0.96, P = 0.01). However, there were no significant differences in IAA (OR = 0.18, 95% CI: -0.28 to 0.64, P = 0.45) and WI (OR = 0.13, 95% CI: (-0.40 to 0.66, P = 0.63) and PI (OR = 2.71, 95% CI: -0.29 to 5.71, P = 0.08). In the children subgroup, there were no significant differences in the incidence of IAA (OR = 0.51, 95% CI: -0.06 to 1.09, P = 0.08) between the two groups. The overall incidence of postoperative complications (OR = 0.46, 95% CI: 0.02-0.90, P = 0.04), incidences of WI (OR = 0.43, 95% CI: 0.14-0.71, P = 0.01) and PI (OR = 0.75, 95% CI: 0.10-1.39, P = 0.02) were significantly higher than those in the non-drainage group. Conclusion: This meta-analysis concluded that prophylactic AD did not benefit from appendectomy, but increased the incidence of related complications, especially in children with CA. Thus, there is insufficient evidence to support the routine use of prophylactic AD following appendectomy.

Efficacy evaluation of nilotinib treatment in different genomic subtypes of gastrointestinal stromal tumors: A meta-analysis and systematic review.

Nilotinib has been used as a third-line drug for gastrointestinal stromal tumors (GISTs) after a failure of sunitinib. In this study, we aimed to evaluate the efficacy of nilotinib in different genomic subtypes of GISTs. We searched the English articles through EMBASE, Cochrane Library and PubMed Database regarding to the use of nilotinib on GISTs, which published up to February 15, 2019. Inclusion criteria were: GISTs patients received nilotinib in a clinical trial and had detailed genetic subtype records (such as KIT exon 9, KIT exon 11, or PDGFRA mutations, or wild-type). The clinical benefit rate was used to assess the efficacy of nilotinib. A total of 3 studies involving 218 GISTs were included in this meta-analysis. The overall OR (KIT group vs WT group) was 3.26 (95% CI: 1.14-9.28; P = 0.027, Pheterogeneity = 0.613). The overall OR in KIT exon 11 group vs WT group was 5.30 (95% CI: 1.79-15.68; P = 0.003, Pheterogeneity = 0.409). The overall OR in KIT exon 9 group vs WT group was 0.13 (95% CI: 0.02-0.86; P = 0.035, Pheterogeneity = 0.229). The overall OR in KIT exon 11 group vs exon 9 group was 9.96 (95% CI: 0.39-254.66; P < 0.0001, Pheterogeneity = 0.024). Different genotypes of GISTs showed different responses to nilotinib, and KIT exon 11-mutant GISTs mostly benefited from nilotinib, followed by KIT exon 9-mutant or WT one.

The feasibility of laparoscopic TSME preserving the left colic artery and superior rectal artery for upper rectal cancer.

BACKGROUND: Laparoscopic tumor-specific mesorectal excision (TSME) preserving the left colic artery and superior rectal artery is still a technically challenging procedure. We conducted this study to demonstrate the feasibility of this procedure for upper rectal cancer. METHODS: A total of 184 patients with upper rectal cancer were retrospectively analyzed in our cancer center between April 2010 and April 2017. These patients were treated with either laparoscopic TSME (n = 46) or laparoscopic total mesorectal excision (TME) (n = 138). In the TSME group, the left colonic artery and superior rectal artery were preserved while they were not in the TME group. RESULTS: The operation time in the TSME group was longer than that in the TME group (218.56 ± 35.85 min vs. 201.13 ± 42.65 min, P = 0.004). Furthermore, the number of resected lymph nodes in the TSME group was greater than that in the TME group (19.43 ± 9.46 vs. 18.03 ± 7.43, P = 0.024). The blood loss between the TSME and TME groups was not significant. No mortality occurred in either the TSME or TME groups. One patient in the TME group underwent conversion to laparotomy. The total postoperative complication rates in the TSME and TME groups were 8.7% and 17.4%, respectively. There was no difference in severe complications between the two groups (anastomotic leakage and stenosis). CONCLUSIONS: Laparoscopic TSME preserving the left colic artery and superior rectal artery can be safely conducted for upper rectal cancer.

Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. METHODS: Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. RESULTS: Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367-0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342-0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. CONCLUSIONS: In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.

Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients.

OBJECTIVE: The mechanism underlying colon cancer metastasis remain unclear. This study aimed to elucidate the genes alteration during the metastasis of colon cancer and identify genes that crucial to the metastasis and survival of colon cancer patients. METHODS: The dataset of primary and metastasis tissue of colon cancer, and dataset of high and low metastasis capability of colon cancer cells were selected as training cohort, and the overlapped differentially expressed genes (DEGs) were screened from the training cohort. The functional enrichment analysis for the overlapped DEGs was performed. The prognostic value of overlapped DEGs were analyzed in The Cancer Genome Atlas dataset, and a gene signature was developed using genes that related to the overall survival (OS). The prognostic value of the gene signature was further confirmed in a validation cohort. RESULTS: A total of 184 overlapped DEGs were screened from the training cohort. Functional enrichment analysis revealed the significant gene functions and pathways of the overlapped DEGs. Four hub genes (3-oxoacid CoA-transferase 1, actinin alpha 4, interleukin 8, integrin subunit alpha 3) were identified using protein-protein network analysis. Six genes (aldehyde dehydrogenase 2, neural precursor cell expressed, developmentally down-regulated 9, filamin A, lamin B receptor, twinfilin actin binding protein 1, serine and arginine rich splicing factor 1) were closely related to the OS of colon cancer patients. A gene signature was developed using these six genes based on their risk score, and the validation cohort indicated that the prognostic value of this gene signature was high in the prediction of colon cancer patients. CONCLUSIONS: Our study demonstrates a gene profiles related to the metastasis of colon cancer, and identify a six-gene signature that acts as an independent biomarker on the prognosis of colon cancer.

Genome­scale analysis to identify potential prognostic microRNA biomarkers for predicting overall survival in patients with colon adenocarcinoma.

The aim of the present study was to identify potential prognostic microRNA (miRNA) biomarkers for colon adenocarcinoma (COAD) prognostic prediction using the dataset of The Cancer Genome Atlas (TCGA). The genome­wide miRNA sequencing dataset and corresponding COAD clinical information were downloaded from TCGA. Prognosis­related miRNA screening was performed by genome­wide multivariable Cox regression analysis and used for prognostic signature construction. Ten miRNAs (hsa­mir­891a, hsa­mir­6854, hsa­mir­216a, hsa­mir­378d­1, hsa­mir­92a­1, hsa­mir­4709, hsa­mir­92a­2, hsa­mir­210, hsa­mir­940 and hsa­mir­887) were identified as prognostic miRNAs and used for further prognostic signature construction. The 10­miRNA prognostic signature showed good performance in prognosis prediction (adjusted P<0.0001; adjusted hazard ratio, 4.580; 95% confidence interval, 2.783­7.538). In the time­dependent receiver operating characteristic analysis, the area under the curve was 0.735, 0.788, 0.806, 0.806, 0.775 and 0.900 for 1­, 2­, 3­, 4­, 5­ and 10­year COAD overall survival prediction, respectively. Comprehensive survival analysis suggested that the 10­miRNA prognostic signature is an independent prognostic factor in COAD, with a better performance in COAD overall survival prediction than other traditional clinical parameters. Functional enrichment indicated that the corresponding target genes were significantly enriched in multiple biological processes and pathways, including regulation of cell proliferation, cell cycle, cell growth, and Wnt and transforming growth factor­ß signaling pathways. In conclusion, our present study identified a 10­miRNA expression signature that may serve as a potential prognostic biomarker in COAD patients.

Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer.

Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), α polypeptide (ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64-0.99), ADH 1B (class 1), ß polypeptide (ADH1B; log-rank P=1.9×10-05; HR=0.65; 95% CI: 0.53-0.79) and ADH 5 (class III), χ polypeptide (ADH5; log-rank P=0.0011; HR=0.73; 95% CI: 0.6-0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43-0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3-0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29-0.98), ADH 4 (class II), π polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35-0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35-0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01-2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation.

Prognostic and clinical significance of syndecan-1 in colorectal cancer: a meta-analysis.

BACKGROUND: Syndecan-1 plays a vital role in the suppression, transformation, and migration of several cancer types, including colorectal cancer (CRC). However, the prognostic and clinical significance of syndecan-1 in CRC remains conflicting. Therefore, we performed a meta-analysis to clarify this relationship. METHODS: A comprehensive literature search for relevant studies published up to December 2014 was performed using PubMed, EMBASE, and Ovid library database. The odds ratio (OR) and pooled hazard ratio (HR) with their 95 % confidence intervals (CI) were used to estimate the effects. RESULTS: Ten studies with 888 CRC patients were selected for evaluation. The results showed that syndecan-1 expression was lower in CRC tissue than in normal colorectal tissue (OR = 0.02, 95 % CI = 0.00-0.09), and lower in the advanced stage than in the early stage (OR = 2.24, 95 % CI = 1.14 - 4.42). Additionally, syndecan-1 expression was higher in well and moderately differentiated CRC than in poorly differentiated CRC (OR = 2.91, 95 % CI = 1.21-6.98); no significant difference was found in patients with or without lymph node metastasis (OR = 0.91, 95 % CI = 0.34-2.43) and distant metastasis (OR = 0.89, 95 % CI = 0.19-4.21). The pooled results showed that syndecan-1 expression was not associated with survival in CRC patients (HR = 0.93, 95 % CI = 0.86-1.01). CONCLUSION: This meta-analysis indicated that loss of syndecan-1 expression is associated with CRC development, histological differentiation, and clinical stage, but not with lymph node metastasis and distant metastasis. In addition, these findings fail to support the prognostic significance of syndecan-1 in CRC.