Development of a necroptosis-related prognostic model for uterine corpus endometrial carcinoma.

Necroptosis is a recently identified caspase-independent form of cell death which plays a significant role in the onset and progression of cancer. MicroRNAs (miRNAs) are vital for the development of uterine corpus endometrial carcinoma (UCEC) because they are an important regulatory component in necroptosis. This study developed a new necroptosis-related miRNAs profile to predict the prognosis of patients with UCEC. The TCGA-UCEC cohort's RNA sequencing data, consisting of 534 tumor samples and 33 normal samples, was downloaded. Ten differentially expressed miRNAs related to necroptosis were identified. A prediction model for necroptosis-related miRNAs was then created through COX regression and nomograms analysis. Clinical and pathological parameters were integrated to construct a nomogram and evaluate the model. Prognosis-related miRNAs were further used to predict target genes, and functional analysis was conducted to explore the potential mechanisms of these target genes. Subsequently, immune infiltration analysis was performed using transcriptome data to identify immune genes associated with prognosis, and the expression levels of target gene was validated using UCEC tissues. We identified 7 up-regulated miRNAs (hsa-miR-577, hsa-miR-7-5p, hsa-miR-210-3p, hsa-miR-210-5p, hsa-miR-200a-5p, hsa-miR-141-3p, hsa-miR-425-5p) and 3 down-regulated miRNAs (hsa-miR-7-2-3p, hsa-miR-383-5p, hsa-miR-29a-3p). The risk signature was based on univariate and multivariate COX analyses, constructed using 2 independent prognostic factors and miRNAs (hsa-miR-425-5p, hsa-miR-7-5p) associated with necroptosis. Nomograms demonstrated the prognostic value of risk level, age, FIGO stage, and histological type. Kaplan-Meier analysis revealed significant differences in overall survival (OS) outcomes associated with the expression of hsa-miR-425-5p (P < 0.001) and hsa-miR-7-5p (P = 0.015). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations indicated that these miRNAs play crucial roles in tumor development, metastasis, and prognosis. Immune infiltration analysis showed decreased infiltration of CD8+ T cells, CD8+ T cells, NK cells, and M1 macrophages in normal tissues. Subsequently, a necroptosis-related immune gene significantly associated with prognosis (THRB) was identified, western blot and immunohistochemical staining confirmed the differential expression of THRB in normal endometrial tissues and tumor. Our findings demonstrate a close association between necroptosis and UCEC. The two necroptosis-related miRNAs used in this study may serve as valuable prognostic markers for UCEC patients, and are associated with immune cell infiltration. This suggests that necroptosis may be involved in the development of UCEC through its interaction with immune responses.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

Prognostic impact of tumor size on patients with metastatic colorectal cancer: a large SEER-based retrospective cohort study.

Given the poor prognosis of metastatic colorectal cancer (mCRC), this research aimed to investigate the correlation between tumor size and prognosis, and develop a novel prediction model to guide individualized treatment. Patients pathologically diagnosed with mCRC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015, and were randomly divided (7:3 ratio) into a training cohort (n = 5597) and a validation cohort (n = 2398). Kaplan-Meier curves were used to analyze the relationship between tumor size and overall survival (OS). Univariate Cox analysis was applied to assess the factors associated with the prognosis of mCRC patients in the training cohort, and then multivariate Cox analysis was used to construct a nomogram model. The area under the receiver-operating characteristics curve (AUC) and calibration curve were used to evaluate the predictive ability of the model. Patients with larger tumors had a worse prognosis. While brain metastases were associated with larger tumors compared to liver or lung metastases, bone metastases tended to be associated with smaller tumors. Multivariate Cox analysis revealed that tumor size was an independent prognostic risk factor (HR 1.28, 95% CI 1.19-1.38), in addition to the other ten variables (age, race, primary site, grade, histology, T stage, N stage, chemotherapy, CEA level and metastases site). The 1-, 3-, and 5-year OS nomogram model yielded AUC values of more than 0.70 in both the training and validation cohorts, and its predictive performance was superior to that of the traditional TNM stage. Calibration plots demonstrated a good agreement between the predicted and observed 1-, 3-, and 5-year OS outcomes in both cohorts. The size of primary tumor was found to be significantly associated with prognosis of mCRC, and was also correlated with specific metastatic organ. In this study, we presented the first effort to create and validate a novel nomogram for predicting 1-, 3- and 5-year OS probabilities of mCRC. The prognostic nomogram was demonstrated to have an excellent predictive ability in estimating individualized OS of patients with mCRC.

Intraindividual Tumor Heterogeneity of Mismatch Repair Status in Metastatic Colorectal Cancer.

Heterogeneous mismatch repair (MMR) status in metastatic colorectal cancer (mCRC) may associate with refractoriness to immunotherapy. We aimed here to study the concordance in MMR status between primary and paired metastasis in mCRC. Our study included 84 patients diagnosed with mCRC with primary and matched metastatic cancers. Immunohistochemistry was used to determine the MMR status of primary lesions and matched metastases. Pooled analysis of 913 cases was used to evaluate the prevalence and organ specificity of MMR status heterogeneity. The correlations between MMR pattern heterogeneity and clinical outcomes were analyzed. MMR status heterogeneity between primary and corresponding metastatic sites was exhibited by 10 (11.9%) patients. The prevalence of the heterogeneous MMR phenotype was significantly higher in primary tumors with deficient MMR (dMMR) than with proficient MMR (pMMR), which was verified in the pooled analysis ( P <0.001). Among patients with a dMMR primary tumor, the discrepancy was detected in liver, lung, ovary, peritoneum, and distant lymph node metastases. However, the discrepancy was confined to liver (26/440) or peritoneum (7/112) ( P =0.02) in patients with a pMMR primary tumor. Patients with or without MMR status heterogeneity experienced comparable overall survival ( P =0.452). Heterogeneous MMR patterns generally existed in a subset of patients with mCRC, particularly those with dMMR primary tumors. Testing the metastatic site may be valuable because the discordance of MMR status may potentially affect immune surveillance and immunotherapy.

The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch-anal anastomosis: A meta-analysis.

BACKGROUND: To date, a few studies indicated that probiotics are beneficial to pouchitis, but no meta-analyses summarized the outcomes of probiotics in pouchitis in detail. OBJECTIVE: This meta-analysis discusses probiotics in the prevention of pouchitis for patients after ileal pouch-anal anastomosis (IPAA) and the relationship between probiotics preventive effect and the duration of therapy and history. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from inception until February 2022. Risk ratio (RR), mean difference (MD) and their 95% confidence interval (CI) were analyzed by Review Manager 5.3. The subgroup analysis was also performed to explore the agent for influencing outcomes. RESULTS: A total of 8 studies were included in this meta-analysis. The incidence of pouchitis in probiotics was significantly lower than that in the control (RR = 0.19, 95%CI [0.12, 0.32], P⁢ï⁢»â¢ 0.00001), and the PDAI (pouchitis disease activity index) in probiotics was also significantly lower (MD =-5.65, 95%CI [-9.48, -1.83]). After the subgroup analysis, we found that probiotics work better in the short-term (RR = 0.12, 95%CI [0.04, 0.40], P= 0.0004), but may not achieve the desired effect in the long-term (RR = 1.20, 95%CI [0.40, 3.60], P= 0.75). CONCLUSIONS: Probiotics are beneficial in the prevention of pouchitis after IPAA, especially in the short-term.

Development and validation of a prognostic nomogram for extrahepatic bile duct adenocarcinoma.

Objective: The aim of this study is to establish a prognostic nomogram for patients with extrahepatic bile duct adenocarcinoma (EBDA). Methods: From the Surveillance, Epidemiology, and End Results database, we retrieved clinical data from 1,485 patients diagnosed with EBDA between 2004 and 2015. These patients were randomly assigned to either the training or validation group in a ratio of 2:1. Cox proportional risk regression models were used to analyze the association of each variable with overall survival (OS). Univariate and multifactorial Cox regression analyses were performed to identify prognostic factors, and prognostic nomograms were created on the basis of the results of Cox multifactorial regression analysis. Performance was assessed by calibration curves and ROC curves. Internal validation was performed using the validation cohort. The Kaplan-Meier method was used to perform log-rank constructions for different risk groups. Results: The results indicated that age, race, N and M stages of tumor-lymph node metastases based on AJCC version 6, surgery, and chemotherapy were independent prognostic factors for OS in patients with EBDA. The constructed nomograms showed decent classification in predicting both 3- and 5-year survival rates. The calibration curves also show a high degree of agreement between the predicted and actual operating systems. Conclusions: The nomogram that we constructed provides a relatively accurate and applicable prediction of survival outcome in patients with EBDA, which helps to provide reference and guidance for patient treatment.

Temporal heterogeneity of HER2 expression in metastatic gastric cancer: a case report.

Gastric cancer is a disease with high heterogeneity, and this heterogeneity may result in an uneven distribution of subclones with varied genetic properties at disease locations (spatial heterogeneity) or temporal changes in subclonal composition (temporal heterogeneity). We present the case of a 69-year-old woman with metastatic gastric cancer who presented for axillary lymph node enlargement and underwent axillary lymphadenectomy. Pathological evidence showed human epidermal growth factor receptor 2 (HER2)(3+). Abdominal computed tomography revealed a mass in the gastric body, gastroscopic biopsy showed HER2(3+). After tumor shrinkage by preoperative translational chemotherapy (oxaliplatin, calcium folate, fluorouracil) and targeted therapy (trastuzumab), she had laparoscopic-assisted total gastrectomy. However, HER2 immunohistochemistry was found to be diffusely negative in the surgically removed tissue, and there was no evidence of HER2 amplification in the whole exon sequencing either. After 10 months of trastuzumab treatment, her disease progressed. Although trastuzumab treatment was initially beneficial, the residual HER2-negative subclones may cause tumor recurrence and metastasis due to temporal heterogeneity, as shown in this case.