ArticleJournal of clinical medicine2022
Serum Proteins, HMMR, NXPH4, PITX1 and THBS4; A Panel of Biomarkers for Early Diagnosis of Hepatocellular Carcinoma.
Article in Journal of clinical medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting NXPH4/ALDH1L2 signaling suppresses enzalutamide resistance in prostate cancer.Cell death discovery · 2026Article
- Taurocholic acid induces intrahepatic cholangiocyte cell proliferation via activating NRAS and YAP1.PloS one · 2026Article
- Extracellular Matrix-Associated Biomarkers for Hepatocellular Carcinoma: Insights From Machine Learning and Single-Cell Analysis.International journal of genomics · 2026Article
- Transcriptional and epigenetic regulation of CaBioinformatics advances · 2026Article
- Consensus artificial intelligence-driven prognostic signature for predicting the prognosis of hepatocellular carcinoma: a multi-center and large-scale study.NPJ precision oncology · 2025Article
- Article
- PITX1 as a grading, prognostic and tumor-infiltrating immune cells marker for chondrosarcoma: a public database-based immunoassay and tissue sample analysis.Frontiers in oncology · 2025Article
- Role of Epigenetic Factors in Determining the Biological Behavior and Prognosis of Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2024Article
- Deciphering the Molecular Complexity of Hepatocellular Carcinoma: Unveiling Novel Biomarkers and Therapeutic Targets Through Advanced Bioinformatics Analysis.Cancer reports (Hoboken, N.J.) · 2024Article
- High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma.Journal of gastrointestinal oncology · 2024Article
- Article
- Construction of diagnostic models for the progression of hepatocellular carcinoma using machine learning.Frontiers in oncology · 2024Article
- Forkhead box protein K1‑regulated neurexophilin 4 promotes proliferation, metastasis and glycolysis in colorectal cancer.Experimental and therapeutic medicine · 2023Article
- An immune and epigenetics-related scoring model and drug candidate prediction for hepatic carcinogenesis via dynamic network biomarker analysis and connectivity mapping.Computational and structural biotechnology journal · 2023Article
- PITX1 plays essential functions in cancer.Frontiers in oncology · 2023Review
- Construction of a Novel Diagnostic Model Based on Ferroptosis-Related Genes for Hepatocellular Carcinoma Using Machine and Deep Learning Methods.Journal of oncology · 2023Article
- NXPH4 Used as a New Prognostic and Immunotherapeutic Marker for Muscle-Invasive Bladder Cancer.Journal of oncology · 2022Article
- Increased Expression of NXPH4 Correlates with Immune Cell Infiltration and Unfavorable Prognosis in Hepatocellular Carcinoma.Journal of oncology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The high morbidity rate of hepatocellular carcinoma (HCC) is mainly linked to late diagnosis. Early diagnosis of this leading cause of mortality is therefore extremely important. We designed a gene selection strategy to identify potential secretory proteins by predicting signal peptide cleavage sites in amino acid sequences derived from transcriptome data of human multistage HCC comprising chronic hepatitis, liver cirrhosis and early and overt HCCs. The gene selection process was validated by the detection of molecules in the serum of HCC patients. From the computational approaches, 10 gene elements were suggested as potent candidate secretory markers for detecting HCC patients. ELISA testing of serum showed that hyaluronan mediated motility receptor (HMMR), neurexophilin 4 (NXPH4), paired like homeodomain 1 (PITX1) and thrombospondin 4 (THBS4) are early-stage HCC diagnostic markers with superior predictive capability in a large cohort of HCC patients. In the assessment of differential diagnostic accuracy, receiver operating characteristic curve analyses showed that HMMR and THBS4 were superior to α-fetoprotein (AFP) in diagnosing HCC, as evidenced by the high area under the curve, sensitivity, specificity, accuracy and other values. In addition, comparative analysis of all four markers and AFP combinations demonstrated that HMMR-PITX1-AFP and HMMR-NXPH4-PITX1 trios were the optimal combinations for reaching 100% accuracy in HCC diagnosis. Serum proteins HMMR, NXPH4, PITX1 and THBS4 can complement measurement of AFP in diagnosing HCC and improve identification of patients with AFP-negative HCC as well as discriminate HCC from non-malignant chronic liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.