This repository is for the manuscript entitled "Targeting oncomucin-driven immunosuppression improves the efficacy of K-rasG12D inhibition in pancreatic cancer" published in Gastroenterology. PMID: 42191046 DOI: 10.1053/j.gastro.2026.04.041
The code used to generate Figures 1A-F,H; 2A,C-J; 3B,C,E-I; and 4B, as well as Supplementary Figures 1; 2B-F; 3; 4D-F; 5; 6; 7; 8A-D; 9; 10A-D,F; 16; 17A; and 18A,D is available in the R Notebooks (PDF or HTML). Use https://htmlpreview.github.io/ to preview HTML file.
While the R Notebooks provide the source code for all data and plots, the final manuscript figures include aesthetic and layout refinements made specifically for publication.
Background: The manuscript leverages decades of our experience in mucin biology and pancreatic ductal adenocarcinoma (PDA) to redefine the paradigm of mucins, which are among the most abundantly expressed glycoproteins in PDA, yet their collective functional contribution to disease progression remains underexplored. Our current study uses single-cell and spatial transcriptomics, multiplexed staining of patient samples, and novel murine models to systematically define the expression and roles of PDA-associated mucins (oncoMUCs; MUC4, MUC5AC, and MUC16). Overall, our mechanistic findings prompted a therapeutic strategy in which multiple oncomucin downregulation (via Istradefylline) synergizes with K-ras inhibition (MRTX1133) to restore CD8⁺ T-cell function, dampen immune checkpoint expression, and ultimately significantly reduce tumor burden. We believe oncoMUCs represent a fundamental, underrecognized barrier to therapeutic success in PDA due to their structural complexity and capacity to coordinate large-scale oncogenic signaling. Therefore, comprehensive characterization of their collective contribution and strategic targeting is essential for the success of cancer therapies.
Please refer to the full manuscript for more details. If you find our work useful in your research or if you use parts of this code, please cite our paper: Bhyravbhatla N, Alsafwani ZW, Thapa I, et al. Targeting Oncomucin-driven Immunosuppression Improves the Efficacy of K-rasG12D Inhibition in Pancreatic Cancer. Gastroenterology. Published online May 25, 2026. doi:10.1053/j.gastro.2026.04.041 Author names in bold designate shared co-first authorship.
Output and processed data files are available upon request from Sushil Kumar (skumar@unmc.edu) and Surinder K Batra (sbatra@unmc.edu).
Analyses were done in R using RStudio. In addition, each R notebook will include the required packages in the first section, "Load R packages".
| Dataset | Data Type | Organsim | Source |
|---|---|---|---|
| GSE201333 | Single-cell | Homo sapiens | Tabula Sapiens - Pancreas |
| CRA001160 | Single-cell | Homo sapiens | CRA001160 data |
| GSE154778 | Single-cell | Homo sapiens | GSE154778 data |
| GSE235315 | Spatial (Visium) | Homo sapiens | GSE235315 data |
| GSE199102 | Spatial (GeoMx) | Homo sapiens | GSE199102 data |
| GSE202051 | Single-nucleus | Homo sapiens | GSE202051 data |
| GSE228502 | Single-cell | Mus musculus | GSE228502 data |
| File | Source |
|---|---|
| PAAD_CRA001160_CellMetainfo_table.tsv | PAAD_CRA001160_CellMetainfo_table |
| PAAD_GSE154778_CellMetainfo_table.tsv | PAAD_GSE154778_CellMetainfo_table |
| PAAD_curated_survival.txt | PAAD_curated_survival |
| moffit_subtype_gene_lists.RData | moffit_subtype_gene_lists |
| RactomePathways_ID_name.txt | RactomePathways_ID_name |
DataProcessing: Main data processing CRA001160, GSE154778, and integrated CRA001160 & GSE154778. Please refer to the R notebooks guide file for detailed information about the input and output of each R notebook.
R Notebooks Main Figures
| R Notebook Name | Main Figure |
|---|---|
| ExpressionPanMUC | Figure 1A |
| SurvivalAnalysis | Figure 1C, 2B, 3K, 4G |
| Exp_oncoMUC_coExp_Integrated | Figure 1D-E, 1I, 2A, 2C |
| Exp_oncoMUC_coExp | Figure 1F |
| DEGs_pathways_MUC_coExp | Figure 2D-F |
| Moffitt_analysis | Figure 2G, 2I-J |
| PatientGrouping | Figure 2H |
| DEGs_pathways_oncoMUC_group_immune | Figure 3A-B |
| Immune_Analysis_ICs | Figure 3E-G, 3I |
| Spatial_Transcriptomics_Analysis | Figure 3H |
| MAPK_signaling_Integrated | Figure 4B |
| UNC5B_Selection_Analysis | Figure 4F |
This repo uses the GNU General Public License v 3.0.