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BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC.MethodsWe initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance.ResultsThe serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression.ConclusionsOur data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

Background: Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC.Methods: Combined with CRC-associated autoantibodies discovered by serological proteome and multiplex analyses, 26 predefined autoantibodies were evaluated in 315 samples (130 CRCs, 75 advanced adenomas, and 110 healthy controls) by protein microarray analysis. Autoantibodies with potential detection value were verified by enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the accuracy of the biomarkers.Results: Four serum autoantibodies (ALDH1B1, UQCRC1, CTAG1, and CENPF) showed statistically different levels between patients with advanced neoplasm (CRC or advanced adenoma) and controls in microarray analysis, which were validated by ELISAs. Among the four biomarkers, the ALDH1B1 autoantibody showed the highest detection value with area under the curve (AUC) values of 0.70 and 0.74 to detect CRC and advanced adenoma with sensitivities of 75.68 and 62.31% and specificities of 63.06 and 73.87%, respectively. By combining the four biomarkers, the performance was improved with an AUC of 0.79 to detect CRC and advanced adenomas.Conclusion: The ALDH1B1 autoantibody has a good potential for early detection of CRC and advanced adenoma, and measuring serum autoantibodies against tumor-associated antigens may improve detection of early CRC.

Rotor syndrome, a rare autosomal-recessive genetic disorder characterized by conjugated hyperbilirubinemia, is caused by biallelic pathogenic variants in both SLCO1B1 and SLCO1B3 genes. Long interspersed nuclear elements (LINEs) make up about 17% of the human genome and insertion of LINE-1 in genes can result in genetic diseases. In the current study, we examined SLCO1B1 and SLCO1B3 genes in two Chinese patients diagnosed with Rotor syndrome based on laboratory tests. In one patient, a novel exon 4 inversion variant was identified. This variant may have been induced by LINE-1 retrotransposon insertion into SLCO1B3 intron 3, and was identified using genome walking. Splicing assay results indicated that the exon inversion, resulting in SLCO1B3 exon 4 (122 bp) exclusion in the mature mRNA, might generate a premature termination codon. Here, we describe an exon inversion contributing to the molecular etiology of Rotor syndrome. Our results may inform future diagnoses and guide drug prescriptions and genetic counseling.

IntroductionWith the depletion of wild Astragali Radix (WA) resources, imitated-wild Astragali Radix (IWA) and cultivated Astragali Radix (CA) have become the main products of Astragali Radix. However, the quality differences of three growth patterns (WA, IWA, CA) and different growth years of Astragali Radix have not been fully characterized, leading to a lack of necessary scientific evidence for their use as substitutes for WA.MethodsWe innovatively proposed a multidimensional evaluation method that encompassed traits, microstructure, cell wall components, saccharides, and pharmacodynamic compounds, to comprehensively explain the quality variances among different growth patterns and years of Astragali Radix.Results and discussionOur study showed that the quality of IWA and WA was comparatively similar, including evaluation indicators such as apparent color, sectional structure and odor, thickness of phellem, diameter and number of vessels, morphology of phloem and xylem, and the levels and ratios of cellulose, hemicellulose, lignin, sucrose, starch, water-soluble polysaccharides, total-saponins. However, the content of sucrose, starch and sorbose in CA was significantly higher than WA, and the diameter and number of vessels, total-flavonoids content were lower than WA, indicating significant quality differences between CA and WA. Hence, we suggest that IWA should be used as a substitute for WA instead of CA. As for the planting years of IWA, our results indicated that IWA aged 1-32 years could be divided into three stages according to their quality change: rapid growth period (1-5 years), stable growth period (6-20 years), and elderly growth period (25-32 years). Among these, 6-20 years old IWA exhibited consistent multidimensional comparative results, showcasing elevated levels of key active components such as water-soluble polysaccharides, flavonoids, and saponins. Considering both the quality and cultivation expenses of IWA, we recommend a cultivation duration of 6-8 years for growers. In conclusion, we established a novel multidimensional evaluation method to systematically characterize the quality of Astragali Radix, and provided a new scientific perspective for the artificial cultivation and quality assurance of Astragali Radix.