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Anti-FIR?exon2 autoantibody as a novel indicator for better overall survival in gastric cancer.

ABSTRACT: There is no clinically available biomarker for efficiently indicating the overall survival or therapy response of gastric cancer (GC). The autoantibodies (Abs) in the sera of anti-far-upstream element-binding protein-interacting repressor-lacking exon2 (FIR?exon2), anti-sorting nexin 15, and anti-spermatogenesis and oogenesis-specific basic helix-loop-helix 1 were markedly higher in GC patients than in healthy donors (HDs). These Abs were identified by large-scale serological identification of antigens by recombinant cDNA expression cloning screenings and their expression levels were evaluated by amplified luminescence proximity homogeneous assay. In particular, compared with age-matched HDs, the level of anti-FIR?exon2 Abs in GC patients was significantly higher (P < .001). The Spearman's rank correlation analysis between anti-FIR?exon2 Abs and clinically available tumor markers such as carcinoembryonic antigen (CEA) was statistically insignificant, indicating that FIR?exon2 Abs is an independent biomarker. We performed receiver-operating curve analysis to evaluate the anti-FIR?exon2 Ab as a candidate biomarker with CEA and carbohydrate antigen 19-9 (CA19-9). The overall survival of GC patients with high anti-FIR?exon2 Abs titer was significantly favorable (P = .04) than that of GC patients who were below detection level of anti-FIR?exon2 Abs. However, clinical stages were not apparently correlated with the levels of anti-FIR?exon2 Ab, CEA, and CA19-9. In conclusion, anti-FIR?exon2 Abs detected in GC patients is a potential biomarker for monitoring a better prognosis. Hence, anti-FIR?exon2 Abs is a promising biomarker for indicating better overall survival of gastric cancer patients.

SUBMITTER: Kobayashi S

PROVIDER: S-EPMC7894018 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Anti-FIRΔexon2 autoantibody as a novel indicator for better overall survival in gastric cancer.

Kobayashi Sohei S Hiwasa Takaki T Ishige Takayuki T Kano Masayuki M Hoshino Tyuji T Rahmutulla Bahityar B Seimiya Masanori M Shimada Hideaki H Nomura Fumio F Matsubara Hisahiro H Matsushita Kazuyuki K

Cancer science 20210102 2

There is no clinically available biomarker for efficiently indicating the overall survival or therapy response of gastric cancer (GC). The autoantibodies (Abs) in the sera of anti-far-upstream element-binding protein-interacting repressor-lacking exon2 (FIRΔexon2), anti-sorting nexin 15, and anti-spermatogenesis and oogenesis-specific basic helix-loop-helix 1 were markedly higher in GC patients than in healthy donors (HDs). These Abs were identified by large-scale serological identification of a ...[more]

PMID: 33306856

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Project description:BackgroundNeutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients' prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis.MethodsWe obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO-Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis.ResultsSeven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p<0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006).ConclusionOverall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.

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Anti-FIR?exon2 autoantibody as a novel indicator for better overall survival in gastric cancer.

Publications

Anti-FIRΔexon2 autoantibody as a novel indicator for better overall survival in gastric cancer.

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