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Comparison of clinicopathological parameters, prognosis, micro-ecological environment and metabolic function of Gastric Cancer with or without Fusobacterium sp. Infection.

ABSTRACT: Background: Fusobacterium sp. plays a crucial role in the tumorigenesis and development of gastrointestinal tumors. Our research group previously disclosed that Fusobacterium sp. was more abundant in gastric cancer (GC) tissues than adjacent non-cancerous (NC) tissues. However, Fusobacterium sp. did not exist in all GC tissues and the differentiated features of GC with or without Fusobacterium sp. infection is not clear. Methods: The expression data of 61 GC tissues came from 16S rRNA gene sequencing. Comparison groups were defined based on sOTU at the genus level of Fusobacterium sp., which was performed by the Qiime2 microbiome bioinformatics platform. We used Chi-square and Fisher's exact test to compare clinicopathological parameters, and used Kaplan-Meier analysis, Cox univariate and multivariate analysis to compare prognosis. Micro-ecological environment comparison was characterized by 16S rRNA gene sequencing, and the metabolic function prediction was applied by PICRUSt2. Results of microbial diversity, differential enrichment genus and metabolic function in GC with or without Fusobacterium sp. infection was validated with 229 GC tissues downloaded from an independent cohort in ENA database (PRJNA428883). Results: The infection rate of Fusobacterium sp. in 61 GC tissues was 52.46% and elderly GC patients were more prone to Fusobacterium sp. infection. GC patients infected with Fusobacterium sp. were more likely to have tumor-infiltrating lymphocytes and p53 expression. The microbial diversity and microbial structure showed significant differences between two GC tissue groups with 42 differential enrichment genera. The metabolic function of Fusobacterium sp.-positive GC tissues was related to the biosynthesis of lysine, peptidoglycan, and tRNA. The differences in microbial structure, the existence of some differential enrichment genera and the metabolic function of Fusobacterium sp.-positive GC tissues, were then validated by 229 GC tissues of an independent cohort. Conclusions: Fusobacterium sp. infection can affect the phenotypic characteristics, micro-ecological environment, and metabolic functions of GC, which may provide a basis for further exploring the relationship between Fusobacterium sp. infection and carcinogenesis of GC.

SUBMITTER: Nie S

PROVIDER: S-EPMC7797643 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundExcision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic diseases and cancers. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.MethodsIn this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) in 109 paired GC and para-cancerous normal tissue samples. The mRNA expression was detected in 36 pairs of tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis to explore the function and regulation networks of ERCC6 and ERCC8 in GC.ResultsIndividual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. ERCC6 mRNA expression showed no difference in GC and paired tissues, while ERCC8 mRNA was significantly decreased in GC tissues. Protein expression of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated that the OS was longer when ERCC6 protein expression and ERCC8 mRNA expression increased, and double negative ERCC6-ERCC8 expression was associated with a short OS. Bioinformatics analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. KEGG pathway showed that ERCC6/ERCC8 related gene sets were mainly involved in the regulation of PI3K/AKT/mTOR pathway. Direct physical interactions were found between ERCC6 and ERCC8.ConclusionsIndividual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Protein expression of ERCC6, ERCC6-ERCC8, and mRNA expression of ERCC8 were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and may regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

Project description:BackgroundCopines-1 (CPNE1) is a soluble membrane-binding protein that includes two tandem C2 domains at the N-terminus and a C terminal A domain. Importantly, it is associated with the prognosis of various tumors, but there are only a few studies regarding the role of CPNE1 in gastric cancer (GC). This study aimed to explore the clinicopathological significance and prognostic potential of CPNE1 expression in GC.MethodsData from the TIMER2.0 and UALCAN were analyzed to assess CPNE1 mRNA levels in GC. The prognostic role of CPNE1 mRNA was examined via the Kaplan-Meier plotter. CPNE1 protein expression in tumor tissues was analyzed via immunohistochemistry of clinical samples from 99 GC patients. The relationship of CPNE1 expression with clinicopathological parameters and overall survival (OS) was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival curves.ResultsCopines-1 mRNA levels were higher in GC tissues than in adjacent normal tissue (ANT) (p < 0.05). Further, high CPNE1 mRNA expression indicated poor OS (p = 9.4 e-10) and was significantly associated with first progression (FP) (p = 1.6 e-06) and post-progression survival (PPS) (p = 1.5 e-12). In addition, CPNE1 protein expression was higher in GC tissues than in ANT (p < 0.0001). Moreover, CPNE1 high expression was significantly related to advanced tumor-node-metastasis (TNM) stage (p = 0.004), lymph node metastasis (p = 0.003), and vascular invasion (p = 0.001). Kaplan-Meier analysis showed that GC patients with high expression CPNE1 group had worse OS than low expression group (p = 0.003). Univariate analysis showed that age (hazard ratio [HR] = 1.992; 95% confidence interval [CI], 1.009-3.934; p = 0.047), advanced TNM stage (HR = 4.941; 95% CI, 2.052-11.897; p = 0.000), tumor invasion (HR = 3.472; 95% CI, 1.349-8.937; p = 0.010), lymph node metastasis (HR = 8.846; 95% CI, 2.708-28.897; p = 0.000), vascular invasion (HR = 3.237; 95% CI, 1.521-6.891; p = 0.002), nervous invasion (HR = 2.324; 95% CI, 1.205-4.479; p = 0.012), and CPNE1 expression (HR = 3.464; 95% CI, 1.440-8.334; p = 0.006) were correlated with OS. In the multivariate analysis, age (HR = 2.514; 95% CI, 1.264-4.999; p = 0.009), lymph node metastasis (HR = 8.441; 95% CI, 2.553-27.906; p < 0.05), and CPNE1 expression (HR = 2.549; 95% CI, 1.051-6.186; p = 0.039) were significant prognostic predictors for GC.ConclusionsCopines-1 overexpression in GC is significantly associated with poor prognosis. Thus, CPNE1 levels may serve as a prognostic biomarker in GC patients.

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Comparison of clinicopathological parameters, prognosis, micro-ecological environment and metabolic function of Gastric Cancer with or without Fusobacterium sp. Infection.

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