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Non-invasive liquid biopsy based on transcriptomic profiling for early diagnosis of occult peritoneal metastases in locally advanced gastric cancer

ABSTRACT: Gastric cancer (GC) remains one of the leading causes of cancer-related death worldwide, especially in East Asian countries. Despite advances in treatment, patients with locally advanced gastric cancer (LAGC) still have a poor prognosis due to the high incidence of metastasis and recurrence. Peritoneal metastasis is particularly occult and difficult to detect by conventional imaging techniques at an early stage. Existing imaging methods lack high sensitivity and are difficult to detect early metastatic lesions. Although diagnostic laparoscopy has high sensitivity, it is invasive and difficult to use routinely. Therefore, innovative diagnostic methods are urgently needed. Transcriptomics methods can provide a comprehensive understanding of the biological state of cancer, especially showing potential in the early detection of GC and peritoneal metastasis. Our objective is to provide a more sensitive diagnostic method in the latent stage of peritoneal metastasis by identifying the RNA expression pattern of cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289037 | GEO | 2025/04/23

REPOSITORIES: GEO

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Project description:Background: Gastric cancer (GC) remains the third leading cause of cancer death worldwide due to the absence of sensitive and specific biomarkers for its early detection. 5-hydroxymethylcytosine (5hmC)-enriched gene profiles and regions show tissue-specific and tumor specific, and cell-free DNA (cfDNA) 5hmC modification feature sequencing provides a robust tool for gastric cancer detection.Methods: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the 5hmC modification of cfDNA. Significantly differential 5hmC modification genes were identified to construct a gastric cancer diagnostic model. The data set from Gene Expression Omnibus consisted of 61 gastric cancer patients, 90 healthy individuals and 22 benign gastric disease controls was used as an external testing set to test the robustness of the diagnostic model. Results: The vast majority of 5hmC peaks were distributed in the gene body, accounting for more than 90% of the total 5hmC peaks in both the GC and control groups. The diagnostic model was developed based on five different 5hmC modification genes, FBXL7, PDE3A, TPO, SNTG2 and SXBP5. The model could clearly distinguish gastric cancer patients from controls in the training (AUC=0.95, sensitivity=88.6%, specificity=94.3%), validation (AUC=0.87, sensitivity=73.3%, specificity=93.3%) and testing (AUC=0.90, sensitivity=81.9%, specificity=90.2%) sets. The predicted risk scores of the controls were significantly lower than those of GC patients in our own data (P<0.001) or GEO external testing data (P<0.001), but no significant difference was observed between different TNM stage groups (P=0.09 and 0.66). Furthermore, the risk scores of healthy and benign gastric disease controls in the testing set were also not different (P=0.10). Conclusions: The characteristics of 5hmC in cfDNA are specific to GC patients, and the diagnostic model constructed by the 5hmC features of five genes could effectively identify GC patients.

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Non-invasive liquid biopsy based on transcriptomic profiling for early diagnosis of occult peritoneal metastases in locally advanced gastric cancer

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