A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a type of cancer that arises from the glandular epithelial cells that produce mucus in the colon. COAD is influenced by various factors, including genetics, environment and lifestyle. The outcome of COAD is determined by the tumor stage, location, molecular characteristics and treatment. Disulfidptosis is a new mode of cell death that may affect cancer development. We discovered genes associated with disulfidptosis in colon adenocarcinoma and proposed them as novel biomarkers and therapeutic targets for COAD. We analyzed the mRNA expression data and clinical information of COAD patients from The Cancer Genome Atlas (TCGA) database and Xena databases, extracted disulfidptosis-related genes from the latest reports on disulfidptosis. We used machine learning to select key features and build a signature and validated the risk model using data from the Gene Expression Omnibus (GEO) database and Human Protein Atlas (HPA). We also explored the potential biological functions and therapeutic implications of the disulfidptosis-related genes using CIBERSORTx and GDSC2 databases. We identified four disulfidptosis-related genes: TRIP6, OXSM, MYH3 and MYH4. These genes predicted COAD patient survival and modulated the tumor microenvironment, drug sensitivity and immune microenvironment. Our study reveals the importance of disulfidptosis-related genes for COAD prognosis and therapy. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings may facilitate personalized cancer treatment.

Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis.

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of "carcinoma" and could affect pathways of "Integrated Cancer Pathway" and "Generic transcription pathway" respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein-protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.

What is the context? Gastrointestinal (GI) tumors are now responsible for the majority of cancer-related mortalities worldwide.In the majority of cases of cancer, curative treatments are not recommended at the time of diagnosis. In this case, early screening and diagnosis is very important for overall tumor prognosis. Liquid biopsy emerged as a newly introduced minimally invasive approach for cancer diagnosis by detecting blood analytes as tumor-educated platelets (TEPs). Compared to tissue-based biopsies, liquid biopsies are less invasive, easy to access, convenient for serial tracking and better in eliminating intratumoral spatial heterogeneity. In recent years, specific gene signatures have been identified for cancer diagnosis, prognosis and prediction based on gene profiling data of TEPs. However, most of these studies were performed on the independent platelet profile datasets published on the Gene Expression Omnibus (GEO) database, which may harbor enormous heterogeneity. Additionally, few study revealed TEP mRNA functions and roles in GI tumors. Therefore, there's the need of using an integrated method to re-analyze these data, so we can gain new insights for GI tumor diagnosis.What is new? Herein, through network-based RNA-seq meta-analysis, we identified the CDK1-HSPA5 signature in TEPs that has the potential as a biomarker for diagnosing GI tumors. This is the first time, to our knowledge, that a shared transcriptional signature of tumor-educated platelets has been identified in human GI tumor patients based on meta-analysis. Additionally, we found the two-gene signature has potential value for metastatic GI tumor diagnosis. We also demonstrated that HSPA5 may have different roles in blood and tumor cells, so its expression deregulation in distinct types of tissue may have opposing diagnostic and prognostic values.What is the impact? Our work provides a novel biomarker for platelet-based GI tumor prediction and diagnosis, which may also be used as novel targets for thrombosis prevention during cancer development in the future.

Robotic natural orifice specimen extraction surgery versus conventional robotic resection for patients with colorectal neoplasms.

Background: Laparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups. Methods: From March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable. Results: Patients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable. Conclusion: Robotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.

Differences in examination results of small anastomotic fistula after radical gastrectomy with afterward treatments: A case report.

BACKGROUND: Gastrografin swallow, methylthioninium chloride test, and computed tomography (CT) are the main methods for postoperative anastomotic fistula detection. Correct selection and application of examinations and therapies are significant for the early diagnosis and treatment of small anastomotic fistulas after radical gastrectomy, which are conducive to postoperative recovery. CASE SUMMARY: A 44-year-old woman underwent radical total gastrectomy for laparoscopic gastric cancer. The patient developed a fever after surgery. The methylthioninium chloride test and early CT suggested no anastomotic fistula, but gastrografin swallow and late CT showed the opposite result. The fistula was successfully closed using an endoscopic clip. The methylthioninium chloride test, gastrografin, and CT performed on different postoperative dates for small esophagojejunostomy fistulas are different. The size of the anastomotic fistula is an important factor for the success of endoscopic treatment. CONCLUSION: The advantages and limitations of the diagnosis of different examinations of small esophagojejunostomy fistulas are noteworthy. The size of the leakage of the anastomosis is an important basis for selecting the repair method.

PPARGC1A affects inflammatory responses in photodynamic therapy (PDT)-treated inflammatory bowel disease (IBD).

BACKGROUND: Chronic inflammation of the gastrointestinal tract is a feature of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Targeting inflammatory signaling represents promising strategy for IBD treatment regimens. METHODS: Dextran sulfate sodium (DSS)-induced colitis model was established in mice. Histopathological examinations were conducted by H&E staining and IHC staining. IL-1ß, IL-10, and TNF-α were tested by ELISA kits. TargetScan was used to predict miRNAs that target PPARGC1A and luciferase activity assay was performed to validate the predicted binding. RESULTS: DSS-induced acute colitis model was successfully established in mice; photodynamic therapy (PDT) treatment partially improved DSS-induced colonic damages and cell inflammation. Microarray assays and integrative bioinformatics analysis identified PPARG coactivator 1 alpha (PPARGC1A) as a significantly differentially-expressed gene in PDT-treated IBD compared with non-treated IBD. PPARGC1A expression was downregulated in IBD clinical samples, DSS-induced colitis mice colons, and DSS-stimulated colonic epithelial cells, whereas partially upregulated by PDT treatment in DSS-stimulated cells. Single DSS stimulation significantly promoted cellular inflammation; PDT partially attenuated, whereas sh-PPARGC1A transduction further enhanced DSS effects on cancer cell inflammation. In colitis mice, DSS decreased PPRA-α and PPRA-γ proteins in mice colons; the in vivo effects of DSS were partially attenuated by PDT treatment, whereas amplified by sh-PPARGC1A transduction. Upstream miR-301a-3p targeted and inhibited PPARGC1A expression. CONCLUSIONS: Collectively, PPARGC1A, which is downregulated in DSS-induced acute colitis and DSS-stimulated colonic epithelial cells, could be upregulated by PDT treatment. PPARGC1A knockdown could attenuate PDT therapeutic effects on DSS-induced acute colitis and DSS-stimulated colonic epithelial cells.