Immune Gene Signatures Converge on FLT3 in Prostate Cancer Analysis

Researchers at Xuzhou Medical University report in Frontiers in Oncology, in the journal’s genitourinary oncology section, that the gene encoding FMS-like tyrosine kinase 3, known as FLT3, emerges as a focal point where immune-associated transcriptional signals and tumor-cell behavior intersect in prostate cancer. Because bulk transcriptomic data blend signals from malignant, stromal, and immune cells within a single measurement, the team combined bulk gene-expression profiling with single-cell RNA sequencing maps and a separate program of cell-line experiments. Screening 502 sample records from 497 prostate cancer patients, the investigators identified 64 genes that appeared both in differential expression analyses linked to ImmuneScore, a computational estimate of immune infiltration, and in a co-expression module derived from the same data. When this shared gene list was compared against four functional gene sets, only two candidates survived the cross-reference: FLT3 and AIM2.

The immune-side evidence rests on correlations rather than demonstrated mechanisms. FLT3 expression in the bulk tumor data correlated with several immune-cell signatures, and the strength of those associations differed by cell type: the relationships were stronger for total T-cell and B-cell signatures than for the signature of CD8-positive T cells, the cytotoxic subset often emphasized in tumor immunology. Single-cell transcriptomic maps added a spatial dimension to the finding, suggesting that FLT3 expression in prostate tumors is located primarily in cells annotated as monocytes rather than in malignant epithelial cells. Taken together, the tissue analyses support an association between FLT3 and immune-associated transcriptional signals, but the authors are explicit that this pattern does not establish how, or whether, FLT3 influences immune activity within tumors.

The second strand of the study examined what happens when FLT3 is removed from prostate cancer cell lines. In DU145 and 22Rv1 cells, two independent small interfering RNAs targeting FLT3 reduced cell growth and colony formation, indicating that the gene contributes to proliferative capacity in these models. Knockdown also reduced readouts of migration and invasion in Transwell assays, and it altered markers associated with epithelial-mesenchymal transition, the phenotypic program through which epithelial tumor cells acquire motile and invasive characteristics. The use of two independent targeting RNAs strengthens the internal consistency of the cell-line results, since concordant effects from distinct molecules reduce the likelihood that the observed phenotypes stem from off-target artifacts of a single reagent.

The authors draw a careful boundary between the two halves of the study. The cell-line findings, they state, describe a separate in vitro phenotype and do not establish how FLT3 relates to lymphocyte infiltration in patient tissue. In other words, showing that FLT3 knockdown slows growth and migration in DU145 and 22Rv1 cells is not equivalent to showing that FLT3 expression drives immune-cell recruitment or exclusion in prostate tumors. The bulk transcriptomic correlations are likewise vulnerable to confounding, because ImmuneScore-associated differential expression reflects the mixed cellular composition of each sample rather than the behavior of any single cell population. The study, as the authors summarize, does not establish prognostic utility for FLT3 or demonstrate an immune-regulatory mechanism; the correlations, the single-cell localization, and the knockdown phenotypes remain distinct lines of evidence that have not yet been connected.

What the work does provide is a defined agenda for follow-up. The convergence of ImmuneScore-linked differential expression, co-expression module membership, and functional gene-set comparison on FLT3 and AIM2 marks both genes as candidates worth pursuing in prostate cancer, with AIM2, a gene involved in innate immune sensing, receiving less attention in the present analysis than FLT3. The single-cell suggestion that FLT3 is expressed in monocytes points toward myeloid-lineage cells as a priority for future investigation, while the knockdown results in DU145 and 22Rv1 cells invite testing in additional cellular contexts, including models that retain more faithful representations of the prostate tumor microenvironment. The authors frame their conclusions accordingly: the observations support further study of FLT3 in distinct cellular contexts, without establishing prognostic value or causal immune effects. For a gene best known in other malignancies, the prostate cancer data now place FLT3 at the junction of immune signatures and tumor-cell phenotypes, where association, localization, and perturbation experiments await integration.

Subject of Research: FLT3 expression and immune-associated transcriptional signatures in prostate cancer

Article Title: FLT3 expression and immune-associated transcriptional signatures in prostate cancer

Article References: Cui, Y., Song, T., Wang, X., Wan, Z., & Mao, L. (2026). FLT3 expression and immune-associated transcriptional signatures in prostate cancer. Frontiers in Oncology, 16, Article 1970520. https://doi.org/10.3389/fonc.2026.1970520

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1970520

Keywords: prostate cancer, FLT3, AIM2, immune infiltration, single-cell RNA sequencing, tumor microenvironment, transcriptomics, cell migration, epithelial-mesenchymal transition, genitourinary oncology, expression, immune-associated