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Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.
Subject(s)
Adenoma , Biomarkers, Tumor , Colorectal Neoplasms , Disease Progression , Feces , Metabolomics , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Feces/chemistry , Adenoma/metabolism , Adenoma/diagnosis , Adenoma/pathology , Adenoma/blood , Metabolomics/methods , Animals , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/blood , Mice , Male , Female , Early Detection of Cancer/methods , Metabolome , Middle Aged , Oleic Acid/metabolism , Oleic Acid/blood , AgedABSTRACT
Gynecomastia can be caused by neurofibromas but has rarely been reported. The present case report describes the clinical appearance, diagnosis, and therapy of a rare combination of a 14 year-old adolescent male unilateral severe gynecomastia with NF-1 neurofibromatosis. In this particular case, we successfully performed minimally invasive surgery using endoscopic mastectomy, which not only resulted in a satisfactory appearance but also confirmed the presence of neurofibroma type 1 by detecting typical immunohistochemical indicators associated with the disease. Additionally, we analyzed the gene responsible for the disease, c.1431del: p. F477Lfs*21, based on the patient's family history.
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Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.
Subject(s)
COVID-19 , Depression , Diarrhea , Fecal Microbiota Transplantation , Humans , Fecal Microbiota Transplantation/methods , COVID-19/therapy , COVID-19/complications , Diarrhea/therapy , Diarrhea/microbiology , Diarrhea/virology , Male , Female , Double-Blind Method , Middle Aged , Depression/therapy , Prospective Studies , Adult , Aged , Feces/microbiology , Feces/virology , SARS-CoV-2 , Treatment Outcome , Aspartate Aminotransferases/blood , Gastrointestinal MicrobiomeABSTRACT
Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.
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Copy number alterations are crucial for the development of gastric cancer (GC). Here, we identified Transmembrane Protein 65 (TMEM65) amplification by genomic hybridization microarray to profile copy-number variations in GC. TMEM65 mRNA level was significantly up-regulated in GC compared to adjacent normal tissues, and was positively associated with TMEM65 amplification. High TMEM65 expression or DNA copy number predicts poor prognosis (P < 0.05) in GC. Furtherly, GC patients with TMEM65 amplification (n = 129) or overexpression (n = 78) significantly associated with shortened survival. Ectopic expression of TMEM65 significantly promoted cell proliferation, cell cycle progression and cell migration/invasion ability, but inhibited apoptosis (all P < 0.05). Conversely, silencing of TMEM65 in GC cells showed opposite abilities on cell function in vitro and suppressed tumor growth and lung metastasis in vivo (all P < 0.01). Moreover, TMEM65 depletion by VNP-encapsulated TMEM65-siRNA significantly suppressed tumor growth in subcutaneous xenograft model. Mechanistically, TMEM65 exerted oncogenic effects through activating PI3K-Akt-mTOR signaling pathway, as evidenced of increased expression of key regulators (p-Akt, p-GSK-3ß, p-mTOR) by Western blot. YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase) was identified as a direct downstream effector of TMEM65. Direct binding of TMEM65 with YWHAZ in the cytoplasm inhibited ubiquitin-mediated degradation of YWHAZ. Moreover, oncogenic effect of TMEM65 was partly dependent on YWHAZ. In conclusion, TMEM65 promotes gastric tumorigenesis by activating PI3K-Akt-mTOR signaling via cooperating with YWHAZ. TMEM65 overexpression may serve as an independent new biomarker and is a therapeutic target in GC.
Subject(s)
Proto-Oncogene Proteins c-akt , Stomach Neoplasms , Humans , 14-3-3 Proteins/metabolism , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Transformation, Neoplastic , Glycogen Synthase Kinase 3 beta/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Transcription Factors/metabolismABSTRACT
While Salvia chinensis Benth (commonly known as "Shijianchuan" in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects.
Subject(s)
Colorectal Neoplasms , Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Proto-Oncogene Proteins c-akt , Network Pharmacology , Phosphatidylinositol 3-Kinases , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
We report the case of a female who was cured of hemorrhagic esophageal varices caused by paroxysmal nocturnal hemoglobinuria (PNH) through transjugular intrahepatic portosystemic shunt (TIPS) treatment. PNH complicated by portal vein and visceral veins thrombosis without hepatic veins is extremely rare, and as such, it is easy to incorrectly treat due to lack of awareness. Hemorrhagic esophageal varices due to PNH with PVT have been reported in one case in 1974, and here, we report the second.
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OBJECTIVE: To assess the potential use of plasma microRNAs (miRNAs) in diagnosis of acute venous thromboembolism (VTE). METHODS: Using BGISEQ-500 sequencing technology, we analyzed the miRNA profile of paired plasma samples from the acute and chronic phases of four patients with unprovoked VTE. Using real-time quantitative polymerase chain reaction (RT-qPCR), we verified nine upregulated named miRNAs in the acute phase in the plasma samples of 54 patients with acute VTE and 39 controls. We then compared the relative expression of the 9 candidate miRNAs between the acute VTE and control group, and plotted the receiver operating characteristic (ROC) curves of the differentially expressed miRNAs. We chose the miRNA with the greatest area under curve (AUC) to evaluate the effect of miRNA on coagulation and platelet function in the plasma samples of 5 healthy volunteers. RESULTS: The plasma levels of miR-374b-3p, miR-660-5p, miR-378a-3p, miR-425-5p, miR-3613-5p, miR-130b-3p, miR-183-5p, and miR-103b were higher in patients with acute VTE than in the controls, with AUCs of 0.6776, 0.6614, 0.6648, 0.6885, 0.8048, 0.6871, 0.7298, and 0.7498, respectively, and P values of 0.0036, 0.0081, 0.0069, 0.0020,<0.0001, 0.0022, 0.0002, andâ<â0.0001, respectively. There were no significant differences in miR-193b-5p level between the acute VTE group and the control group. Fibrinogen (Fib), thrombin- antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), and TAT/plasmin-α2-plasmin inhibitor complex (PIC) were decreased in the miR-3613-5p group when compared with the control group (P < 0.05) and the mean platelet aggregation rate was increased in the miR-3613 group (P < 0.05). CONCLUSION: miRNAs can be potential biomarkers for diagnosing acute VTE, and miR-3613-5p may be involved in the formation, coagulation, and platelet functions in acute VTE.
Subject(s)
MicroRNAs , Venous Thromboembolism , Humans , MicroRNAs/genetics , Venous Thromboembolism/diagnosis , Venous Thromboembolism/genetics , Tissue Plasminogen Activator , Biomarkers , ROC CurveABSTRACT
Purpose: Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer. Methods: Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level. Results: A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells. Conclusion: Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.
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BACKGROUND: Colorectal cancer is a common digestive tract malignancy. This study aimed to expound the functional role of fatty-acid-binding protein 4 (FABP4) and the potential underlying mechanisms in the development of colorectal cancer. METHODS: Several techniques were utilized to investigate the role of FABP4 in colorectal cancer. FABP4 mRNA expression was quantified using Real time-quantitative PCR (RT-qPCR). Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), sphere formation assays and flow cytometry evaluated cell growth, stemness, and apoptosis in SW480 and HT29 cells. Glycolysis was assessed via extracellular acidification rate (ECAR) , lactate production, glucose uptake, adenosine triphosphate (ATP)/adenosine 5'-diphosphate (ADP) ratio, and Glut1 and Elevated lactate dehydrogenase A (LDHA) protein expression. Reactive oxygen species (ROS) levels were analyzed by flow cytometry. Western blot measured the protein expression of FABP4, Proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, Glut1, LDHA, stemness makers (Sox2, Oct4, and ALDHA1), and extracellular regulated protein kinase (ERK)/mammalian target of rapamycin (mTOR) pathway proteins. In vivo experiments, BALB/c nude mice (n = 12) were inoculated with 200 µL HT29 cells (5 × 106 cells) transfected with sh-FABP4 or short hairpin (sh)-negative control (NC), forming two groups with 6 mice each. The in vivo mice tumor model allowed for evaluating FABP4's impact on tumor growth. RESULTS: FABP4 was significantly upregulated in colorectal cancer tissues and cells (p < 0.05). FABP4 knockdown markedly inhibited cell proliferation, stemness, and glycolysis, while promoting apoptosis in these cells (p < 0.05). Additionally, FABP4 depletion led to a significant increase in ROS level (p < 0.05). However, N-acetyl-L-cysteine (NAC) (p < 0.05), a ROS scavenger, mitigates these effects. Furthermore, the effects of FABP4 depletion on cell growth, stemness, glycolysis, and apoptosis in colorectal cancer cells were also retarded by NAC (p < 0.05). Notably, FABP4 knockdown also suppressed the ERK/mTOR pathway, suggesting its regulation via ROS (p < 0.05). In vivo study results showed, FABP4 depletion significantly curbed tumor growth in colorectal cancer (p < 0.05). CONCLUSIONS: These results suggest that FABP4 depletion inhibits colorectal cancer progression by modulating cell growth, stemness, glycolysis and apoptosis. This regulation occurs through the ROS/ERK/mTOR pathway.
Subject(s)
Colorectal Neoplasms , Signal Transduction , Animals , Mice , Reactive Oxygen Species/metabolism , Glucose Transporter Type 1/metabolism , Mice, Nude , TOR Serine-Threonine Kinases/metabolism , Cell Proliferation , Apoptosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Glycolysis , Cell Line, Tumor , Mammals/metabolism , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Fatty Acid-Binding Proteins/pharmacologyABSTRACT
BACKGROUND: Most patients suffering from gynecomastia require treatment to maintain a smooth subcutaneous tissue contour, remove loose skin, and leave a suitable nipple-areolar complex with minimal scarring; hence, surgery has become the prime choice to treat gynecomastia. Based on our experience, Liu and Shang's 2-hole 7-step method works well for these patients. METHODS: From November 2021 to November 2022, a total of 101 gynecomastia patients featuring various Simon grades were included in this study. The patients' basic condition and surgical procedure were recorded in detail. A score of 1 to 5 was given for 6 main aesthetic aspects. RESULTS: With Liu and Shang's 2-hole 7-step method, the operations were successfully completed in all 101 patients. Six patients had Simon grade I, 21 grade IIA, 56 grade IIB, and 18 grade III. The average surgery time was 86.54 (range = 46-144) minutes. The average intraoperative blood loss was 22.7 (range = 10 â¼ 75) mL. The average postoperative drainage time was 2.35 (range = 1-4) days, the drainage volume was 83.35 (range = 13â¼240) mL, and the drainage mainly occurred on the first postoperative day. The scores on all 6 aesthetic aspects were >4 points, which fully affirmed the aesthetic effect of this method. CONCLUSION: Liu and Shang's 2-hole 7-step method is safe and feasible for treating gynecomastia and has been fully affirmed for its efficacy and cosmetic effect. It can be the main option for minimally invasive surgery to treat gynecomastia.
Subject(s)
Breast Neoplasms , Gynecomastia , Lipectomy , Mastectomy, Subcutaneous , Male , Humans , Gynecomastia/surgery , Lipectomy/methods , Treatment Outcome , Mastectomy, Subcutaneous/methods , Breast Neoplasms/surgery , Retrospective Studies , MastectomyABSTRACT
p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. As there is currently no existing study on combining APR-246 with radiation in rectal cancer, our objective was to investigate whether APR-246 could enhance the sensitivity of colorectal cancer cells, regardless of their p53 status, to radiation treatment. The combination treatment had synergistic effects on HCT116p53-R248W/- (p53Mut) cells, followed by HCT116p53+/+ [wild-type p53 (p53WT)] cells, and exhibited an additive effect on HCT116p53-/- (p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared with p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radiosensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in patients with rectal cancer.
Subject(s)
Colorectal Neoplasms , Rectal Neoplasms , Animals , Humans , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Zebrafish/metabolism , Apoptosis/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/radiotherapy , Rectal Neoplasms/genetics , Rectal Neoplasms/radiotherapy , Cell Line, TumorABSTRACT
BACKGROUND: This study aimed to explore whether and to what extent metabolic syndrome (MetS) and its components are associated with in-hospital complications in patients with acute type B aortic dissection after thoracic endovascular aortic repair (TEVAR). METHODS: We retrospectively enrolled 684 patients who had undergone TEVAR. Demographic and clinical data were collected and subgroup analysis, mixed-model regression analysis, scoring systems, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Overall, 684 inpatients were assigned to the poor outcome (n = 90) or no complications (n = 594) group. Compared to the no complications group, the poor outcome group had a higher incidence of MetS (44 [48.9%] vs. 120 [20.2%], P < 0.05). In the subgroup analysis, in-hospital complications were present in 3.1%, 6.6%, 11.9%, 20.7%, 40.0%, and 62.5% of patients in the 6 groups who met the 0, 1, 2, 3, 4, and 5 MetS diagnostic criteria, respectively. On multivariable logistic regression, hypertension (odds ratio [OR]: 2.680; 95% confidence interval [CI]: 1.571-4.570), type 2 diabetes (OR: 2.135; 95% CI: 1.192-3.824), quartiles of body mass index (OR: 1.801; 95% CI: 1.415-2.291), high-density lipoprotein cholesterol (OR: 0.763; 95% CI: 0.611-0.953), and systolic blood pressure (OR: 1.894; 95% CI: 1.486-2.413) were independent factors for in-hospital complications after adjustment for other risk factors. After adjusting for potential confounding factors, MetS was an independent risk factor for in-hospital complications. We established a scoring system for each component and the area under the ROC curve was 0.664 (95% CI: 0.618-0.710) in all patients, 0.672 (95% CI: 0.595-0.749) in patients with MetS, and 0.610 (95% CI: 0.552-0.667) in patients without MetS, as determined by ROC analysis. CONCLUSIONS: MetS, especially the blood pressure component, confers a greater risk of in-hospital complications in patients with acute type B aortic dissection after TEVAR.
Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Diabetes Mellitus, Type 2 , Endovascular Procedures , Metabolic Syndrome , Humans , Endovascular Aneurysm Repair , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Blood Vessel Prosthesis Implantation/adverse effects , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/etiology , Retrospective Studies , Endovascular Procedures/adverse effects , Treatment Outcome , Time Factors , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Risk Factors , Hospitals , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
BACKGROUND: Previous studies have reported that the tumor heterogeneity and complex oncogenic mechanisms of proximal and distal colon cancer (CRC) are divergent. Therefore, we aim to analyze the differences between left-sided CRC (L_cancer) and right-sided CRC (R_cancer), as well as constructing respective nomograms. METHODS: We enrolled 335 colon cancer patients (146 L_cancer patients and 189 R_cancer patients) from The Cancer Genome Atlas (TCGA) data sets, and 102 pairs of color cancer tissue and adjacent normal tissue (51 L_cancer patients and 51 R_cancer patients) from our hospital. Firstly, we analyzed the differences between the L_cancer patients and R_cancer patients, and then established the L_cancer and R_cancer prognostic models using LASSO Cox. RESULTS: R_cancer patients had lower survival than L_cancer patients. R_cancer patients had higher ESTIMATE and immune scores and lower tumor purity. These patterns of expression of immune checkpoint-related genes and TMB level were higher in R_cancer than in L_cancer patients. Finally, we using Lasso Cox regression analyses established a prognostic model for L_cancer patients and a prognostic model for R_cancer patients. The AUC values of the risk score for OS in L_cancer were 0.862 in the training set and 0.914 in the testing set, while those in R_cancer were 0.835 in the training set and 0.857 in the testing set. The AUC values in fivefold cross-validation were between 0.727 and 0.978, proving that the two prognostic models have great stability. The nomogram of L_cancer included prognostic genes, age, pathological M, pathological stage, and gender, the AUC values of which were 0.800 in the training set and 0.905 in the testing set. Meanwhile, the nomogram of R_cancer comprised prognostic genes, pathological N, pathological T, and age, the AUC values of which were 0.836 in the training set and 0.850 in the testing set. In the R_cancer patients, high-risk patients had a lower proportion of 'B cells memory', 'Dendritic cells resting', immune score, ESTIMATE score, immune checkpoint-related genes, and HLA-family genes, and a higher proportion of 'T cells follicular helper', 'Dendritic cells activated', and 'Mast cells activated'. CONCLUSIONS: We found significant differences between L_cancer and R_cancer patients and established a clinical predictive nomogram for L_cancer patients and a nomogram for R_cancer patients. Additionally, R_cancer patients in low-risk groups may be more beneficial from immunotherapy.
Subject(s)
Colonic Neoplasms , Immunotherapy , Humans , Prognosis , Oncogenes , Nomograms , Colonic Neoplasms/geneticsABSTRACT
BACKGROUND: The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). METHODS: Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein - protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. RESULTS: A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. CONCLUSION: Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.
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BACKGROUND: The aim of this study was to explore whether or to what extent metabolic syndrome (METs) and its components were associated with hypoxemia in acute type A aortic dissection (ATAAD) patients after surgery. METHODS: This study involved 271 inpatients who underwent surgery. Demographic and clinical data were collected. Subgroup analysis, mixed model regression analysis, and receiver operating characteristic (ROC) curve analysis were performed, and a scoring system was evaluated. RESULTS: The 271 inpatients were assigned to the hypoxemia group (n = 48) or no hypoxemia group (n = 223) regardless of METs status. Compared to the no hypoxemia group, the hypoxemia group had a higher incidence of METs. Hypoxemia was present in 0%, 3.7%, 19.8%, 51.5%, 90.0% and 100% in the groups of individuals who met the diagnostic criteria of MetS 0, 1, 2, 3, 4 and 5 times, respectively. In the multivariable logistic regression analysis, BMI quartile was still a risk factor for hypoxemia after adjustment for other risk factors. After adjustment for potential confounding factors, METs was an independent risk factor for hypoxemia in several models. After assigning a score for each METs component present, the AUCs were 0.852 (95% CI 0.789-0.914) in all patients, 0.728 (95% CI 0.573-0.882) in patients with METs and 0.744 (95% CI 0.636-0.853) in patients without METs according to receiver operating characteristic analysis. CONCLUSIONS: METs, especially body mass index, confers a greater risk of hypoxemia in ATAAD after surgery.
Subject(s)
Aortic Dissection , Metabolic Syndrome , Aortic Dissection/complications , Aortic Dissection/surgery , Body Mass Index , Humans , Hypoxia/etiology , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , ROC Curve , Risk FactorsABSTRACT
MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. A significant upregulation of miR-17-5p expression was found in colorectal cancer (CRC) tissues by miRNA microarray chip analysis. However, the underlying mechanism of miR-17-5p in CRC is still unclear. The mRNA expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. The biological function of miR-17-5p was demonstrated through CCK-8, colony formation, flow cytometry and transwell assays. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. Transcriptome sequencing and miRNA target prediction software suggested that HSPB2 might be a target gene of miR-17-5p and luciferase reporter detection validated for the first time that miR-17-5p binds directly to the 3'-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2. Taken together, miR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.
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Colorectal cancer (CRC) is one of the most common malignancies and has been a leading cause of cancer-related death worldwide in recent years. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification of various types of RNAs, and it plays a vital role in promoting cancer development. Here, we obtained SNV and transcriptome data of CRC from The Cancer Genome Atlas (TCGA). We demonstrated that most m6A methylation regulators were aberrantly expressed in individuals with CRC. The abnormal expression of m6A regulators was caused by their different copy number variation (CNV) patterns, and alteration of m6A regulators was significantly correlated with prognosis and tumor stage. By using weighted coexpression network analysis (WGCNA), we identified m6A-related long noncoding RNAs (lncRNAs) and mRNAs; then we used least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct m6A-related lncRNA and mRNA prognostic signatures in the TCGA dataset. Furthermore, a nomogram with clinicopathological features, lncRNA risk scores, and mRNA risk scores was established, which showed a strong ability to forecast the overall survival of the individuals with CRC in training and testing sets. In conclusion, m6A methylation regulators played a vital role in affecting the prognosis of subjects with CRC, and m6A-related lncRNAs and mRNAs revealed underlying mechanisms in CRC tumorigenesis and progression.
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PURPOSE: The purpose of this study was to evaluate the association between the distance from the primary intimal tear (PIT) to the left subclavian artery (LSA) (PIT-LSA distance) and the risk of aortic enlargement after thoracic endovascular aortic repair (TEVAR). METHODS: This is a retrospective cohort study. A total of 228 patients were reviewed from the database of the Registry Of type B aortic dissection with the Utility of STent graft (ROBUST) study performed from January 1, 2011, to December 31, 2016. Of them, 196 patients were eligible for analysis. The PIT-LSA distance was defined as the length from the distal edge of the LSA orifice to the proximal edge of the PIT along the centerline of the true lumen. According to the border between zone 3 and zone 4 of the Ishimaru classification, patients were divided into group A (n = 117, PIT-LSA distance ≤ 2 cm) and group B (n = 79, PIT-LSA distance > 2 cm). Thoracic aortic enlargement (TAE) was defined as a thoracic aortic volume increase of ≥20%. Multivariate Cox regression was used to estimate the association between the PIT-LSA distance and risk of TAE after TEVAR. RESULTS: The mean age was 52.3 ± 11.6 years, and 88.8% of patients were male. There were no significant differences between groups in demographic and baseline characteristics. The PIT-LSA distance was 1.1 cm (range, -1.6 to 2.0 cm) in group A, and 2.9 cm (range, 2.1-12.6 cm) in group B. TAE occurred in 27 patients in group A, and 6 in group B. The mean follow-up was 12.4 months (range, 0.10-83.1 months) in group A, and 12.63 months (range, 0.10-82.77 months) in group B. The cumulative 12- and 24-month rates of freedom from TAE were 79.0% and 71.3% in group A, versus 92.5% and 92.5% in group B, respectively. Multivariate Cox regression analysis revealed that the PIT-LSA distance was an independent predictor of TAE after TEVAR (adjusted hazard ratio, 0.66; 95% confidence interval, 0.48-0.90; p = 0.009). CONCLUSION: Patients with a more proximal PIT location have a higher incidence of thoracic aortic enlargement after TEVAR. The location of the PIT in relation to the LSA can be used to identify patients who need closed surveillance after TEVAR or early preemptive intervention.
Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Adult , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Subclavian Artery/diagnostic imaging , Subclavian Artery/surgery , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC). METHODS: Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database. RESULTS: Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717-0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates. CONCLUSIONS: In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.