Tianyu Shen

Background: Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide, highlighting the need for improved prognostic tools. The integration of artificial intelligence (AI) and machine learning (ML) with multi-omics data offers new opportunities for biomarker discovery and risk stratification. Methods: We integrated bulk transcriptomic data from GSE116918 (training, n = 248) and three cross-cohort consistency evaluation cohorts (TCGA-PRAD, GSE70769, GSE46602), focusing on 1087 epithelial–mesenchymal transition (EMT)-associated genes. Using consensus clustering, weighted gene co-expression network analysis (WGCNA), and 91 machine learning algorithm combinations (including Random Forest, Lasso, and CoxBoost), we constructed a prognostic signature. SHAP analysis was used for model interpretability. Single-cell RNA sequencing (scRNA-seq, GSE268307, 10,672 cells) and spatial transcriptomics (10× Genomics Visium FFPE) provided hypothesis-generating evidence; spatial analysis was based on one tissue section. Results: A three-gene signature (INHBA, FAP, ITGBL1) effectively stratified patients into high- and low-risk groups, with the high-risk group showing significantly worse metastasis-free survival (HR = 1.61, 95% CI: 1.39–1.87; 4-year AUC = 0.93 in the training cohort; external AUCs ranged from 0.62 to 0.77). CytoTRACE inferred high differentiation potential of COMP+ fibroblasts, and Monocle3 inferred a transcriptional transition from COMP+ toward NELL2+ fibroblasts. BayesPrism deconvolution suggested that high inferred COMP+ fibroblast abundance was associated with poor prognosis and advanced T stage. NicheNet analysis prioritized BMP7 as a key upstream ligand, with downstream targets enriched in TGF-β signaling and stem cell pluripotency pathways. Conclusions: This study presents a machine learning-based multi-omics framework for prostate cancer risk stratification. The three-gene signature provides a new exploratory prognostic model while inferring a COMP+ to NELL2+ transcriptional transition. These findings may inform future hypothesis-driven studies of treatment sensitivity, pending experimental validation, and demonstrate the value of AI-driven multi-omics integration for precision oncology.

Background: The mechanism by which kinesin-like protein family 20A (KIF20A) influences prostate cancer progression remains unclear. This study aims to investigate the functional role of KIF20A in prostate cancer and its transcriptional regulatory mechanism via activation of activating transcription factor 2 (ATF2). Methods: Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) were used to assess KIF20A expression in prostate cancer tissues. The chi-square tests was used to analysze the association between KIF20A expression and clinical-pathological features of prostate cancer. A stable KIF20A knockdown prostate cancer cell line was established. The effects of KIF20A expression levels on prostate cancer cell proliferation and invasion were investigated through plate cloning and cell invasion assays. JASPAR was used to predict ATF2 binding sites within the KIF20A promoter region, which were validated by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Results: KIF20A expression was significantly elevated in prostate cancer tissue compared to their adjacent non-cancerous tissue controls. Furthermore, high KIF20A expression was significantly correlated with tumor grading and staging, as well as lymph node metastasis factors in prostate cancer patients. Knockdown of KIF20A significantly inhibited the proliferation and invasion of prostate cancer cells. ATF2 bound to the promoter region of the KIF20A gene, thereby promoting KIF20A transcription. Conclusions: Under the transcriptional regulation of ATF2, KIF20A expression is significantly upregulated in prostate cancer tissues, thereby promoting the progression of prostate cancer. KIF20A may serve as an independent prognostic factor influencing the prognosis of prostate cancer patients.

Background: Bladder outlet obstruction (BOO) frequently accompanies benign prostate hyperplasia (BPH) in aging males and often leads to bladder fibrosis, a secondary pathological change that contributes to bladder dysfunction. The role of Cathepsin S (CTSS), a cysteine protease associated with immune responses, in this process remains to be fully elucidated. Methods: Bladder tissues from BOO model mice were analyzed using microarray profiling, followed by Gene Ontology (GO) and pathway enrichment analyses. Candidate genes, including CTSS, C-X-C Motif Chemokine Ligand 17 (CXCL17), and Angiopoietin Like 7 (ANGPTL7), were identified. CTSS was selected for further investigation based on its association with fibrotic processes. The functional role of CTSS in smooth muscle cell hypertrophy and fibrosis was verified both in vivo and in vitro. A co-culture system of smooth muscle cells and monocyte–macrophages was used to explore the underlying mechanism. Results: Microarray and bioinformatic analysis identified CTSS as a key candidate gene associated with immune response in BOO-induced bladder fibrosis. CTSS expression was upregulated in BOO bladders and was demonstrated to promote smooth muscle cell hypertrophy and fibrotic changes. Mechanistically, CTSS mediated proteolytic cleavage of the interleukin-6 receptor (IL-6R) on immune cells, generating soluble IL-6R (sIL-6R). This process facilitated IL-6 trans-signaling, which in turn promoted smooth muscle cell hypertrophy and exacerbated bladder fibrosis. Conclusions: These findings indicate that CTSS contributes to BOO-induced bladder dysfunction and fibrosis by activating IL-6 trans-signaling through cleavage of IL-6R. CTSS may represent a potential therapeutic target for mitigating bladder fibrosis in BPH.

The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT–qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.

Purpose. KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. Methods. Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. Results. KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. Conclusions. Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.

Objective. To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients.Methods. Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot. Immunohistochemical (IHC) staining was used to identify the expression and distribution of KIF20A proteins in the tissue samples. The relationship between the KIF20A expression and the clinical pathology of bladder cancer was analysed. The effect of the differential expression of KIF20A on the prognosis of patients with bladder cancer was analysed by the TCGA database. The plasmid was transfected into the bladder cell lines T24 and 5637 to construct two stable cell lines with knocked down KIF20A. The effect of KIF20A expression on the proliferation and invasion of T24 and 5637 bladder cells was explored in vitro using the abovementioned stable cell lines. The effect of the KIF20A expression on the proliferation of bladder cancer cells was evaluated by a mouse xenograft model.Results. The expression of KIF20A was significantly higher in the bladder cancer tissues than in the adjacent control tissues. The expression of KIF20A was significantly associated with the degree of pathological differentiation of bladder cancer. Patients with a higher expression of KIF20A had a higher tumour grade and a more advanced stage. The mean survival of patients with a high KIF20A expression was significantly lower than the mean survival of patients with a low KIF20A expression. The in vitro experiments demonstrated that the knockdown of KIF20A significantly inhibited T24 and 5637 cell proliferation and invasion. The in vivo experiments showed that the knockdown of KIF20A significantly inhibited the proliferation of the bladder tumours.Conclusion. KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. KIF20A may become an independent factor that affects the prognosis of bladder cancer patients and a therapeutic target for bladder cancer.