SPDEF (SAM Pointed Domain Containing ETS Transcription Factor)

Luminal Androgen Receptor and Molecular Apocrine Breast Cancers constitute a single molecular entity within estrogen receptor-negative breast cancers. The validated four-gene signature enables robust clinical identification and may guide future therapeutic stratification.

Our findings demonstrate the tumor-promoting function of SPDEF in NSCLC by transcriptionally activating BIRC5, highlighting SPDEF as a candidate target for future NSCLC-directed therapies.

Acting as a glycan rheostat, GNASR201C elevates LacdiNAcs at the expense of pro-tumorigenic acidic Lewis epitopes, inhibiting cancer cell invasion and disease progression. LacdiNAcs and 3'-sulfo-LeA/C are mutually exclusive and may serve as markers to risk stratify IPMN patients for surgery.

SPDEF functions as a tumor suppressor in breast cancer, with reduced expression linked to poor outcomes, aggressive molecular features, and epigenetic regulation. These findings highlight SPDEF and DNMT-driven methylation as potential prognostic biomarkers for enhanced risk stratification and targets for novel therapies, particularly in Basal breast cancers.

Our study provides novel insights into the molecular characteristics of Paget cells, and also highlights the critical role of FOXA1 in Paget cell development in EMPD.

Hypomethylation of a specific CpG dinucleotide in the SPDEF promoter may serve as a promising noninvasive blood-based biomarker for the early detection and clinical stratification of prostate cancer.

Mechanistically, NRF2 suppresses IPMN formation through redox-independent transcriptional repression of SPDEF and MUC6, key markers of IPMN. These findings establish NRF2 as a lesion-specific regulator of pancreatic tumorigenesis, providing new molecular insights into PDA progression and potential biomarkers for early detection and risk stratification.

WDR11-DT-induced dual restraints of PARP1 and the HR pathway lead to the accumulation of double-strand breaks as well as synthetic lethal effects of malignant cells, which, thereby, enhances radiosensitivity and inhibits progression of lung cancer. These results extend our current knowledge of radio-biology and elucidate that WDR11-DT may be a new target for boosting cancer radiotherapy.

Multi-compartment correlation analysis revealed three ecosystem-level patterns: (1) Inverse association between Epi_Diff and Epi_pEMT (Spearman R = -0.43); (2) Negative correlation between mCAF1 abundance and cCAF frequency (R = -0.48); (3) TAM(SPP1) dominance inversely correlating with both TAM(C1Q) (R = -0.43) and NK/T infiltration (R = -0.36). These axes suggest a potential hierarchical ecology framework where lineage-specific polarisation and inter-compartment synergies may collectively govern disease progression.

In vitro EEC organoid models also demonstrate SSEA-1+ EECs to exhibit estrogen responsive proliferation evidenced by stronger immunostaining for progesterone receptor and Ki-67. Our data further suggest a more quiescent, less hormone responsive phenotype for SSEA-1+ EECs that co-localize to SOX9+ EECs within in silico analysis, thus validating previous studies.

Combination of PURE-AID with prostate-specific antigen (PSA) and age increases AUROC to 0.80 and reduces 54.3% of unnecessary biopsies with 86.8% sensitivity. Our study provides a new classification system for differentiating high-grade PCa in a workflow- and patient-friendly manner.

SCC-CUPdef patients with positive vs. negative p16-status had significantly longer overall survival (53 vs. 41 Monate, p=0,037), as well as patients with cN1- vs. cN3-status and M0- vs. M1-status.p16-status influences diagnosis and therapy response in patients with SCC-CUP: in p16-positive SCC-CUPinit, primary tumor detection rates were significantly higher than in p16-negative SCC-CUPinit. In patients with SCC-CUPdef, p16-positivity was associated with improved overall survival, albeit to an extent which does not justify therapy de-escalation.