Journal: bioRxiv

Article Title: Cell-of-Origin, not Oncogenic Effect, Determines Desmoplastic Immune Exclusion in KRAS-Driven Liver Cancer

doi: 10.64898/2026.03.24.711280

Figure Lengend Snippet: Multi-omics integration identifies LAMC2, uPA and BSSP-4 as CCA-specific secreted factors. (A) Schematic of the experimental workflow to collect material for secretome and proteome analysis. (B) Venn diagram showing the overlap of PK-induced transcriptional and secretory responses in chol-orgs. Intersections include PK-upregulated genes in chol-orgs from RNA-seq (chol-PK vs chol-WT, bottom-left), PK-upregulated proteins in chol-orgs from secretome (CCM, bottom-right), genes whose PK-induced expression is stronger in interaction effects (interaction contrast, upper-right), and proteins predicted to be secreted according to the Human Protein Atlas (upper-left). (C) Bubble plot showing cross-dataset support for candidate PK-associated genes identified by the integrative analysis in (B). Rows indicate 15 selected genes from (B), and columns indicate the indicated in-house murine result and public human datasets. Dot color encodes z-scored log2 FC (z(LFC). Filled circles indicate significant differences (padj < 0.1) and open circles indicate non-significant results. Dot size reflects statistical strength-log10(padj).

Article Snippet: The antibodies used in this study were: Lamc2 (Proteintech, #19698-1-AP), uPA (Proteintech, #17968-1-AP), BSSP4 (ThermoFisher Scientific, #PA5-47245), and rabbit-IgG (Millipore, #pp64).

Techniques: Biomarker Discovery, RNA Sequencing, Expressing

Journal: bioRxiv

Article Title: Cell-of-Origin, not Oncogenic Effect, Determines Desmoplastic Immune Exclusion in KRAS-Driven Liver Cancer

doi: 10.64898/2026.03.24.711280

Figure Lengend Snippet: LAMC2 and uPA affect HSC activation and impair CCA formation in vivo . (A) Schematic overview of the in vitro fibroblast activation assay, where murine HSCs were treated with CCM from chol-PK and neutralizing antibodies. (B) Scatter plot indicating mRNA expression of Acta2 and Col1a1 in mHSCs treated with Chol-PK CCM and indicated neutralizing antibodies or control IgG. (n=5 from 2 independent experiments). (C) Schematic of scratch assay with mHSCs treated with low FBS (2%) media supplemented with respective recombinant protein. (D) Plot depicting mean relative wound coverage upon scratch injury over time with indicated recombinant protein at different dosage (n≥17 from 3 experiments). (E) Schematic of in vivo validation model: Chol-PK organoids were edited by CRISPR/Cas9 to generate Prss22 -, Lamc2 -, or Plau -deleted lines, which were orthotopically implanted into the liver and harvested at the same time point. (F) Macroscopic images of liver tumors 7 weeks after implantation of indicated lines. (G) Bar plot with respective tumor penetrance per line. (H) Representative histopathology images of liver tumors obtained upon orthotopic implantation of chol-PK and indicated KO lines. Stains as indicated. Red dotted line demarcates the boundary between non-tumor liver (N) and tumor (T). All scale bars are 100 μm. (I) Scatter plot depicting the total CD3 + and CD8 + T cell density per area per tumor for the indicated lines.

Article Snippet: The antibodies used in this study were: Lamc2 (Proteintech, #19698-1-AP), uPA (Proteintech, #17968-1-AP), BSSP4 (ThermoFisher Scientific, #PA5-47245), and rabbit-IgG (Millipore, #pp64).

Techniques: Activation Assay, In Vivo, In Vitro, Expressing, Control, Wound Healing Assay, Recombinant, Biomarker Discovery, CRISPR, Histopathology