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Purpose: The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. Methods: Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. Results: In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). Conclusions: Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC. [ABSTRACT FROM AUTHOR]

Background: The advancements in artificial intelligence (AI) technology for image recognition were propelling molecular pathology research into a new era. Objective: To summarize the hot spots and research trends in the field of molecular pathology image recognition. Methods: Relevant articles from January 1st, 2010, to August 25th, 2023, were retrieved from the Web of Science Core Collection. Subsequently, CiteSpace was employed for bibliometric and visual analysis, generating diverse network diagrams illustrating keywords, highly cited references, hot topics, and research trends. Results: A total of 110 relevant articles were extracted from a pool of 10,205 articles. The overall publication count exhibited a rising trend each year. The leading contributors in terms of institutions, countries, and authors were Maastricht University (11 articles), the United States (38 articles), and Kather Jacob Nicholas (9 articles), respectively. Half of the top ten research institutions, based on publication volume, were affiliated with Germany. The most frequently cited article was authored by Nicolas Coudray et al. accumulating 703 citations. The keyword "Deep learning" had the highest frequency in 2019. Notably, the highlighted keywords from 2022 to 2023 included “microsatellite instability”, and there were 21 articles focusing on utilizing algorithms to recognize microsatellite instability (MSI) in colorectal cancer (CRC) pathological images. Conclusion: The use of DL is expected to provide a new strategy to effectively solve the current problem of time-consuming and expensive molecular pathology detection. Therefore, further research is needed to address issues, such as data quality and standardization, model interpretability, and resource and infrastructure requirements. [ABSTRACT FROM AUTHOR]

Background: The colorectum includes ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Different sites of colorectal cancer (CRC) are different in many aspects, including clinical symptoms, biological behaviour, and prognosis.Purpose: This study aimed to analyse prognosis, genes, bacteria, fungi, and microbial metabolome in different sites of CRC.Methods: The Surveillance, Epidemiology, and End Results (SEER) database and STAT were used to statistically describe and analyse the prognosis in different sites of CRC. RNA sequences of CRC from Broad Institute's GDAC Firehose were re-annotated and reanalysed based on different sites using weighted gene co-expression network analysis (WGCNA). The Kaplan-Meier method was used to analyse the prognosis and Cytoscape was used to construct a drug-target network based on DGIdb databases. Bacterial 16S V3-V4 and fungal ITS V3-V4 ribosomal RNA genes of stool samples were sequenced. Gas chromatography/mass spectrometry (GS/MS) was performed to detect the microbial metabolites in stool samples. Bioinformatics analysis was performed to compare distinct gut microorganisms and microbial metabolites between rectal and sigmoid cancers.Results: The prognosis in CRC with different sites is significantly different. The closer to the anus predicted longer survival time. The difference between genes and co-expression pairs in CRC with different sites were constructed. The relative abundance of 112 mRNAs and 26 lncRNAs correlated with the sites of CRC were listed. Nine differentially expressed genes at different sites of CRC were correlated with prognosis. A drug-gene interaction network contained 227 drug-gene pairs were built. The relative abundance of gut bacteria and gut fungus, and the content of microbe-related metabolites were statistically different between rectal and sigmoid cancers.Conclusions: There are many differences in prognosis, genome, drug targets, gut microbiome, and microbial metabolome in different colorectal cancer sites. These findings may improve our understanding of the role of the CRC sites in personalized and precision medicine. [ABSTRACT FROM AUTHOR]

L-securinine is a natural product extracted and isolated from the leaf of dried Securinega suffruticosa. The aim of the present study was to explore the effects of L-securinine on proliferation, and the methylation profile of the dickkopf-related protein 1 (DKK1) gene in human lung cancer cells and fibroblasts. L-securinine was extracted, isolated and the structure was identified. The cytotoxicity of L-securinine in A549 cells was evaluated by Cell Counting Kit-8 assays. The expression and DNA methylation profile of DKK genes was analyzed by reverse transcription-quantitative polymerase chain reaction and bisulfite sequencing polymerase chain reaction, respectively. L-securinine inhibited the proliferation of lung cancer cells; the half-maximal inhibitory concentration values were 8.92, 4.73 and 3.81 µg/ml, at 24, 36 and 48 h post-treatment, respectively. DKK1, 2 and 3 expression was significantly increased in A549 cells compared with HLF-a cells. L-securinine induced the downregulation of DKK1 in A549 cells in a dose-dependent manner and induced methylation changes at CpG sites in the DKK1 promoter region. L-securinine may be a potential anticancer drug that mediates its effects by altering DKK1 gene methylation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies. [ABSTRACT FROM AUTHOR]

Background: Liver cancer is one of the most common malignant tumors in the world. T cell-mediated antitumor immune response is the basis of liver cancer immunotherapy. Objective: To screen and analyze the RNAs associated with activated memory CD4 T cells and CD8 T cells in liver cancer. Methods : ESTIMATE was used to calculate the stromal and immune scores of tumor samples, which were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) in high and low stromal and immune scores were screened, followed by functional enrichment of overlapped DEGs. We then conducted a survival analysis to identify immune-related prognostic indicators and constructed protein-protein interaction (PPI) networks and ceRNA networks. Finally, chemical small-molecule–target interaction pairs associated with liver cancer were screened. Results: A total of 55,955 stromal-related DEGs and 1811 immune-related DEGs were obtained. The 1238 overlapped DEGs were enriched in 1457 biological process terms and 74 KEGG pathways. In addition, a total of 120 activated memory CD4 T cell-related genes and 309 CD8 T cell-related genes were identified. The survival analysis revealed that upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. EOMES was regulated by has-miR-23b-3p and has-miR-23b-3p was regulated by lncRNA AC104820.2 in the ceRNA network of activated memory CD4 T cell-related genes. In addition, EOMES was regulated by has-miR-23a-3p and has-miR-23a-3p was regulated by lncRNA AC000476.1 in the ceRNA network of CD8 T cells. Conclusion: T cell-related RNAs EOMES, CST7, CD5L, has-miR-23b-3p, and has-miR-23a-3p may be associated with the prognosis of liver cancer. And the molecular characteristics of these T cell-related genes were plotted. Highlights: A total of 309 CD8 T cell-related genes and 120 activated memory CD4 T cell-related genes were screened in liver cancer tumor samples. Forty-four chemical small-molecule–target interaction pairs associated with activated memory CD4 T cells and 276 pairs associated with CD8 T cells were screened. Upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. [ABSTRACT FROM AUTHOR]

Abstract The gut microbiome changes are related to the colorectal cancer (CRC). Chemotherapy is one of the main treatment methods for CRC. To explore the effect of chemotherapy on the gut bacteria and fungi in CRC. Total of 11 advanced CRC patients treated with the FOLFIRI regimen, 15 postoperative CRC patients treated with the XELOX regimen, and corresponding CRC patients without surgery and chemotherapy were recruited. The 16S ribosomal RNA and ITS sequences were sequenced, and bioinformatics analysis was executed to screen for the distinctive gut microbiome. The abundances of Veillonella, Humicola, Tremellomycetes and Malassezia were increased in postoperative CRC patients treated with the XELOX regimen. The abundances of Faecalibacterium, Clostridiales, phascolarctobacterium, Humicola and Rhodotorula were decreased, and the abundances of Candida, Magnusiomyces, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen. The abundances of Humicola, Rhodotorula, and Magnusiomyces were decreased, and the abundances of Candida, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen combined with cetuximab compared with those treated with the FOLFIRI regimen alone. The community structure of gut bacteria and fungi changes in chemotherapy on CRCs. • The abundances of Veillonella , Humicola , Tremellomycetes and Malassezia were increased in postoperative CRC patients treated with the XELOX regimen. • The abundances of Faecalibacterium , Clostridiales , phascolarctobacterium , Humicola and Rhodotorula were decreased in advanced CRC patients treated with the FOLFIRI regimen. • The abundances of Candida , Magnusiomyces , Tremellomycetes , Dipodascaceae , Saccharomycetales , Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen. • The abundances of Humicola , Rhodotorula , and Magnusiomyces were decreased in advanced CRC patients treated with the FOLFIRI regimen combined with cetuximab compared with those treated with the FOLFIRI regimen alone. [ABSTRACT FROM AUTHOR]