Validation of serum cystatin SN detection for diagnosis and poor prognosis of esophageal squamous cell carcinoma.

Background: The identification of effective tumor markers is of paramount importance for the early diagnosis, treatment, and prognosis of esophageal squamous cell carcinoma (ESCC). The present study endeavors to identify efficacious serological markers that can differentiate patients with early-stage ESCC from those with benign esophageal lesions and healthy controls (HC). Cystatin-SN (CST1), an active cysteine protease inhibitor belonging to the Cystatin (CST) superfamily, is implicated in the pathogenesis of inflammation and tumorigenesis. The objective of this investigation is to assess the diagnostic, therapeutic, and prognostic potential of serum CST1 in ESCC. Methods: In our prior RNA sequencing and screening endeavors, we have identified ten genes that are up-regulated in relation to esophageal cancer. Subsequently, we have verified the gene CST1 from the transcriptome data of the The Cancer Genome Atlas Program (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Following this, we conducted an enzyme-linked immunosorbent assay (ELISA) to ascertain the expression levels of CST1 in serum samples from clinical cohorts. Results: The study revealed a significant elevation in serum CST1 levels among patients with early-stage esophageal squamous cell carcinoma (ESCC) (7.41 ± 4.32 ng/ml) compared to those with esophageal benign lesions (4.67 ± 2.43 ng/ml) (p < 0.0001) and healthy controls (4.87 ± 2.77 ng/ml) (p < 0.0001). The diagnostic sensitivity of CST1 for ESCC was 75.68% (specificity 70.83%, AUC 0.775). Combination of CST1 and SCC-Ag exhibited the AUC up to 0.819. Additionally, serum CST1 levels exhibited a significant decrease at 1-2 weeks post-surgery (4.49 ± 3.31 ng/ml) compared to pre-surgery levels (7.68 ± 3.71 ng/ml) (p<0.0001). Survival analysis demonstrated a strong association between high (844/415-1543 d) or low (1490/645-1710 d) serum CST1 levels at diagnosis and overall survival time (p < 0.001). Furthermore, multivariate regression analysis confirmed CST1 (p=0.024, HR=2.023, 95%CI 1.099-3.725) as an independent prognostic factor. Conclusion: Serum CST1 has the potential to function as a diagnostic indicator for distinguishing early-stage esophageal squamous cell carcinoma (ESCC) from individuals with benign esophageal lesions and healthy individuals. Additionally, it could serve as a prognostic predictor and therapeutic efficacy indicator for patients with ESCC.

Comparison of Cerebrospinal Fluid Cellular Analysis by Optical Microscopy and Sysmex XN 9000.

BACKGROUND: This study was designed to compare the body fluid module of Sysmex XN9000 (XN-BF) with optical microscopy (OM) for cerebrospinal fluid (CSF) analysis after two-step cell slide centrifuge (TSCSC), defining the best procedure for CSF optical microscopy analysis. METHODS: Items of RBC, WBC enumeration and differentiation were observed. The cell count and morphologic evaluation of the cellular composition by OM was carried out both with and without two-step cell slide centrifuge (TSCSC) and were compared the data with XN-BF. RESULTS: There were 69.98 ± 4.94 RBC and 36.98 ± 3.39 WBC in one OSCSC microscopic field whereas there were 96.35 ± 5.41 RBC and 66.15 ± 4.85 WBC in one TSCSC microscopic field in the same sample (*200). There was a statistical difference between those two methods (p = 0.000). Excellent correlation was found between total cell count with both OM and XN-BF. The R2 value for RBC and WBC counts were 0.99 and 0.96, respectively. For WBC differential, the R2 values were 0.98 for PMN and 0.70 for MN. Correlation of MN was poorer than PMN. As far as the tumor cell, phagocyte, and plasma cell with high fluorescence were concerned, OM were not consistent with XN-BF. CONCLUSIONS: The TSCSC procedure contributes to the separation of cells and other ingredients. XN-BF displays excellent performance at RBC and WBC cell count except for mononuclear cells, tumor cells, phagocytes, and leukemia cells. which makes it just a practical alternative to total cell (WBC, RBC) count for CSF samples. Detailed morphologic workup of CSF samples is mandated in all cases with meningoencephalitis, elevated cell count, sub-arachnoid hemorrhage and meningeal carcinomatosis, the TSCSC procedure is recommended.

Plasma Macrophage Inhibitory Cytokine-1 as a Complement of Epstein-Barr Virus Related Markers in Identifying Nasopharyngeal Carcinoma.

BACKGROUND: We evaluated the diagnostic value of plasma Macrophage inhibitory cytokine-1 (MIC-1) in distinguishing patients with nasopharyngeal carcinoma (NPC) and explored its complementary role with widely used Epstein-Barr virus (EBV) related markers, EBV capsid antigen-specific IgA (VCA-IgA) and EBV copy number. METHODS: ELISA was used to analyze the plasma MIC-1 levels in 190 NPC patients, 72 VCA-IgA-positive healthy donors (VP), and 219 normal subjects with negative VCA-IgA (VN). 10 pairs of plasma samples before and after radiotherapy were also included. RESULTS: The plasma MIC-1 levels were significantly higher in NPC patients (Median: 678.39 ng/mL) than those in VN and VP (310.29 and 294.59, p < 0.001). Receiver operating characteristic (ROC) curves of the MIC-1 concentrations revealed that the area under the ROC curve (AUC) was 0.790 (95% confidence interval [CI]: 0.748-0.832), with a sensitivity of 63.7%, and a specificity of 85.9% respectively, for distinguishing NPC patients from the healthy donors. Similarly, between NPC and VP, ROC was 0.796 (0.738-0.853) with sensitivity of 63.7%, and specificity of 88.9%. In addition, between NPC and VN, ROC was 0.788(0.744-0.832) with sensitivity of 63.7%, and specificity of 84.9%. Further, we found that MIC-1 could complement VCA-IgA and EBV DNA markers, with a negative rate of 88.9% in VCA-IgA-positive healthy controls, and a positive rate of 59.0% in EBV DNA negative NPC patients, respectively. Also, the MIC-1 plasma concentration dropped significantly after radiotherapy (p = 0.027). CONCLUSIONS: MIC-1 can complement VCA-IgA titers and EBV DNA copy number tests in NPC detection, improve identification of EBV DNA-negative NPC patients, and distinguish NPC from VCA -IgA positive healthy controls.

Integrated analysis of long non-coding RNAs and mRNA profiles reveals potential sex-dependent biomarkers of bevacizumab/erlotinib response in advanced lung cancer.

BACKGROUND: While lung cancer patient outcomes are well-recognized to vary as a function of patient sex, there has been insufficient research regarding the relationship between patient sex and EGFR(Epidermal growth factor receptor) response efficacy. The present study therefore sought to identify novel sex-related biomarkers of bevacizumab/erlotinib (BE) responses in non-small cell lung cancer (NSCLC) patients. METHODS: The exon array data in the Gene Expression Omnibus (GEO) dataset were analyzed in order to identify patterns of mRNA and lncRNA expression associated with BE resistance in NSCLC. These differentially expressed (DE) lncRNAs and mRNAs were identified via DE Analysis Filtering. These DE mRNAs were then assessed for their potential functional roles via pathway enrichment analyses, with overlapping functions possibly associated with the BE resistance. The mRNAs in these overlapping groups were then assessed for their correlations with patient survival, and lncRNA-mRNA co-expression networks were generated for each patient subset. A protein-protein interaction (PPI) network was also generated based upon these DE mRNAs. RESULTS: In females we identified 172 DE lncRNAs and 1766 DE mRNAs associated with BE responses, while in males we identified 78 DE lncRNAs and 485 DE mRNAs associated with such responses. Based on the overlap between these two datasets, we identified a total of 37 GO functions and 18 pathways associated with BE responses. Co-expression and PPI networks suggested that the key lncRNAs and mRNAs associated with these BE response mechanisms weredifferent in the male and female patients. CONCLUSIONS: This work is the first to conduct a global profiling of the relationship between lncRNA and mRNA expression patterns, patient sex, and BE responses in individuals suffering from NSCLC. Together these results suggest that the integrative lncRNA-mRNA expression analyses may offer invaluable new therapeutic insights that can guide the tailored treatment of lung cancer in order to ensure optimal BE responses.