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Biomedical subjects

Yuxiang Wang

Publications and source records attributed to Yuxiang Wang.

4 recordsLinked to original sources

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans

Artificial intelligence-assisted histopathological diagnosis of endocervical gastric-type adenocarcinoma: a multicenter model development and validation study.

Endocervical gastric-type adenocarcinoma (GAS) is one of the most aggressive subtypes of cervical cancer and is frequently underdiagnosed due to morphological ambiguity, leading to delayed diagnosis. Despite the availability of molecular and genomic assays, their high cost, complexity, and limited reproducibility restrict clinical use. This study therefore proposes a highly sensitive artificial intelligence (AI)-assisted diagnostic system for GAS based exclusively on H&E-stained histopathological images. We included 309 slides from 96 GAS cases collected at Peking University Third Hospital from January 2018 to January 2025, representing the largest GAS cohort reported to date for AI research. In addition, we incorporated other morphologically analogous diseases, encompassing a total of 1,320 slides sourced from four categories: normal cervical mucosa (NORM), benign endocervical lesion entities (BELE), HPV-associated adenocarcinoma (HPVA), and endometrioid carcinoma with mucinous differentiation (ECMD). We developed GASPath, based on a novel multiple instance learning framework that efficiently captures fine-grained morphological variations from H&E-stained images. Beyond internal validation, GASPath was evaluated across 12 independent retrospective cohorts and further subjected to large-scale real-world validation on more than 7,000 samples from March 2024 to April 2025. Across three stages, GASPath demonstrated high performance. In internal validation (Stage I), it achieved an accuracy of 0.980 (95% CI 0.977-0.983) and an ROC-AUC of 0.995 (95% CI 0.994-0.997). In external validation (Stage II), the sensitivity reached 0.902 and improved to 0.968 with proposed strategies. For biopsy samples, GASPath achieved an ROC-AUC of 0.990 (95% CI 0.984-0.997). In large-scale real-world deployment (Stage III, n = 7,056), GASPath achieved a balanced accuracy of 0.953, with 100% sensitivity for GAS (45/45 cases correctly identified). The heatmaps highlight morphological features of GAS that are easily underestimated, such as irregular, angulated glands, subtle loss of nuclear polarity, and mild cytologic atypia, which show substantial morphological overlap with other diagnostic categories. GASPath enables high-sensitivity detection of GAS in routine H&E-stained slides, obviating the need for extensive auxiliary testing while preventing underdiagnosis and misdiagnosis. This advancement addresses a critical gap by streamlining diagnostic workflows without compromising accuracy. Its implementation could enable cost-effective, scalable AI-assisted diagnostics, potentially transforming the early detection and management of this aggressive cancer subtype.

Female

Transcriptomic landscape of NK cell-related genes in hepatocellular carcinoma: associations with prognosis and therapeutic response.

Hepatocellular carcinoma (HCC) is a highly aggressive and heterogeneous malignancy, in which natural killer (NK) cells play a crucial role in tumor progression and immune surveillance. This study aimed to characterize the transcriptomic landscape of NK cell-associated genes (NAGs) and explore their associations with clinical outcomes and therapeutic responses in HCC. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we identified key NAGs through comprehensive statistical analyses. Patients were stratified into distinct risk groups based on NAG expression profiles. Low-risk patients demonstrated better survival, higher immune infiltration, and greater predicted sensitivity to immunotherapy, whereas high-risk patients were associated with reduced chemotherapy responsiveness. These findings contribute to a deeper understanding of the immunogenomic features of HCC and provide a basis for developing personalized therapeutic approaches centered on NK cell-related mechanisms.

Hepatocellular carcinoma

CRISPR/Cas9 screenings reveal the role of STX1A and CDK1 in Cathepsin G entering and killing colorectal cancer cells.

Neutrophils are the major populations of white blood cells and have been reported to facilitate cancer metastasis. Meanwhile, emerging evidence has recently suggested the anti-cancer role of neutrophils. Our previous study revealed that CB-839 and 5-FU-treated colorectal cancer (CRC) tumors recruited neutrophils and induced neutrophil extracellular traps (NETs). Cathepsin G (CTSG), which is released during NET formation, enters CRC cells through the receptor for advanced glycation end products (RAGE) and cleaves 14-3-3ε to promote apoptosis. However, the detailed mechanism underlying CTSG's anti-tumor function remains less studied. In this study, we report that CTSG enters CRC cells through RAGE-mediated endocytosis. Knocking out RAGE or inhibiting endocytosis blocks CTSG from entering CRC cells and attenuates CTSG-induced apoptosis. Furthermore, the clathrin coat assembly complex and SNARE proteins were enriched in an arrayed CRISPR/Cas9 screening targeting human membrane trafficking genes. Knocking out SNARE protein STX1A prevents the spread of CTSG in CRC cells and the induction of cleaved PARP. A pooled genome-wide CRISPR/Cas9 screening further identifies the role of CDK1 in the NET-induced killing of CRC cells. Inhibiting CDK1 protected CRC cells from killing by CTSG. Our study reveals novel mechanisms by which CTSG enters and kills CRC cells.

CDK1