Transcription factor Sp1 is multifaceted, with the ability to function as an oncogene or a tumor suppressor, depending on the cellular context. We previously reported that Sp1 is required for the transcriptional activation of the key oncogenes in nasopharyngeal carcinoma (NPC), including B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1) and centromere protein H (CENPH), but the role of Sp1 and its underlying mechanisms in NPC remained largely unexplored. The objective of this study was to investigate the cellular function of Sp1 and to verify the clinical significance of Sp1 as a potential therapeutic target in NPC.

Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).

Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222–3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (p < 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.

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 the 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 multi-centre study comprising 404 individuals. In the application phase, the authors evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms. Results: Through 4D-DIA proteomic analysis, the authors identified seven 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 three EVs surface proteins, FIBG, PDGF-β and TGF-β, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an area under the curve (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-β, and TGF-β as novel diagnostic biomarkers for CRC. 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.

Nasopharyngeal carcinoma (NPC) is a malignant tumor prevalent in Southern China, strongly associated with Epstein-Barr virus (EBV) infection. Accurate diagnosis is critical in determining treatment strategies for NPC. In clinical practice, imaging techniques are the most predominant diagnostic methods, which are costly and may fail to detect small metastatic lesions. Moreover, while EBV antibody and DNA tests contribute to the assessment of tumor progression, they carry the risk of false negatives. To develop novel serum protein biomarkers for late-stage NPC diagnosis, our study included 189 samples, including healthy controls (HCs) and early- or late-stage NPC patients. A high-throughput serum proteomics approach was employed to delineate protein profiles, followed by enzyme-linked immunosorbent assay (ELISA) validation of candidate biomarkers. Our study identified fibronectin 1 (FN1) as a promising serum biomarker for late-stage NPC. The serum levels of FN1 significantly decreased with tumor progression, achieving AUCs of 0.71 and 0.72 in differentiating late-stage NPC patients from HCs and early-stage NPC patients, respectively. Importantly, FN1 demonstrated diagnostic utility in challenging cases, accurately identifying all VCA-IgA-negative and 88.2% EBV DNA-negative patients with late-stage NPC. Combining FN1 with VCA-IgA or EBV DNA test significantly increased diagnostic sensitivity for advanced NPC. Our discovery of FN1 as a biomarker for the late-stage diagnosis of NPC will assist in clinical treatment decisions and improve the prognosis of patients.