Identification and validation of the surface proteins FIBG, PDGF-ß, and TGF-ß on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study.

OBJECTIVES: The absence of non-invasive biomarkers for the early diagnosis of colorectal cancer (CRC) has contributed to poor prognosis. Extracellular vesicles (EVs) have emerged as promising candidates for cancer monitoring using liquid biopsy. However, the complexity of EVs isolation procedures and absence of clear targets for detecting serum-derived EVs have hindered the clinical application of EVs in early CRC diagnosis. METHODS: In the discovery phase, we conducted a comprehensive 4D-DIA proteomic analysis of serum-derived EVs samples from 37 individuals, performing an initial screening of EVs surface proteins. In the technical validation phase, we developed an extraction-free CRC-EVArray microarray to assess the expression of these potential EVs surface proteins in a multicenter study comprising 404 individuals. In the application phase, we evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms. RESULTS: Through 4D-DIA proteomic analysis, we identified 7 potential EVs surface proteins showing significantly differential expression in CRC patients compared to healthy controls. Utilizing our developed high-throughput CRC-EVArray microarray, we further confirmed the differential expression of 3 EVs surface proteins, FIBG, PDGF-ß and TGF-ß, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an AUC of 0.882 in the train set and 0.937 in the test set. Additionally, we predicted the functions and potential origins of these EVs-derived proteins through a series of multi-omics approaches. CONCLUSIONS: Our systematic exploration of surface protein expression profiles on serum-derived EVs has identified FIBG, PDGF-ß, and TGF-ß as novel diagnostic biomarkers for CRC. And the development of CRC-EVArray diagnostic model based on these findings provided an effective tool for the large-scale CRC screening, thus facilitating its translation into clinical practice.

Whole genome sequencing provides evidence for Bacillus velezensis SH-1471 as a beneficial rhizosphere bacterium in plants.

Bacillus is widely used in agriculture due to its diverse biological activities. We isolated a Bacillus velezensis SH-1471 from the rhizosphere soil of healthy tobacco, which has broad-spectrum antagonistic activity against a variety of plant pathogenic fungi such as Fusarium oxysporum, and can be colonized in the rhizosphere of a variety of plants. This study will further explore its mechanism by combining biological and molecular biology methods. SH-1471 contains a ring chromosome of 4,181,346 bp with a mean G + C content of 46.18%. We identified 14 homologous genes related to biosynthesis of resistant secondary metabolite, and three clusters encoded potential new antibacterial substances. It also contains a large number of genes from colonizing bacteria and genes related to plant bacterial interactions. It also contains genes related to environmental stress, as well as genes related to drug resistance. We also found that there are many metabolites in the strain that can inhibit the growth of pathogens. In addition, our indoor pot test found that SH-1471 has a good control effect on tomato wilt, and could significantly improve plant height, stem circumference, root length, root weight, and fresh weight and dry weight of the aboveground part of tomato seedlings. Therefore, SH-1471 is a potential biological control strain with important application value. The results of this study will help to further study the mechanism of SH-1471 in biological control of plant diseases and promote its application.