2. Academic Validation
  3. Prognostic and Immunological Significance of TIPARP in Pancreatic Cancer

Prognostic and Immunological Significance of TIPARP in Pancreatic Cancer

  • Dig Dis Sci. 2025 Nov 24. doi: 10.1007/s10620-025-09546-2.
Hanlin Jiang # 1 2,  Weiqiao Niu # 1 2,  Yujia Pan 3,  Zongying Jiang 1 2,  Jianwu Wu 1 2,  Zhiming Qiao 1 2,  Xinwei Jiang 1 2,  Lining Huang 4 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, China.
  • 2 Gusu School, Nanjing Medical University, Suzhou, 215000, China.
  • 3 Center for Scientific Research and Innovation, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, China.
  • 4 Department of Hepatobiliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215000, China. [email protected].
  • 5 Gusu School, Nanjing Medical University, Suzhou, 215000, China. [email protected].
  • # Contributed equally.
PMID: 41284141 DOI: 10.1007/s10620-025-09546-2
Abstract

Background: Pancreatic ductal adenocarcinoma (PAAD) remains one of the most lethal malignancies, with a 5-year survival rate below 10%. TCDD-inducible poly (ADP-ribose) polymerase (TIPARP) is aberrantly expressed in various tumors, but its mechanistic role and clinical significance in pancreatic Cancer remain unclear.

Methods: We analyzed TIPARP expression patterns and prognostic relevance by integrating data from the TCGA-PAAD (n = 178) and GTEx (n = 171) databases. Single-cell RNA Sequencing, immune infiltration profiling, and Mendelian randomization analyses were conducted to assess cell-type specificity and causal relationships. The biological functions of TIPARP were validated through in vitro assays, and downstream mechanisms were explored via pathway enrichment analysis.

Results: TIPARP was significantly upregulated in pancreatic Cancer tissues and correlated with worse overall survival (P = 5.9e - 3) and progression-free survival (P = 0.01), serving as an independent prognostic risk factor. A TIPARP-based nomogram exhibited strong predictive performance (C-index = 0.666; 5-year AUC = 0.885). Single-cell transcriptomics identified fibroblasts as the primary TIPARP-expressing cell type. Immune profiling revealed that high TIPARP expression was associated with altered immune cell infiltration and positively correlated with immune checkpoint molecules such as PD-L1 and TIM-3. Mendelian randomization confirmed a causal association between genetically predicted TIPARP expression and increased PAAD risk (OR = 1.511, P = 0.008). Functional assays showed that TIPARP promotes cell proliferation, migration, and invasion, while pathway analysis implicated the PI3K-Akt and ECM-receptor interaction signaling cascades.

Conclusion: TIPARP is a novel independent prognostic biomarker and potential therapeutic target in pancreatic Cancer. It contributes to tumor progression by promoting an immunosuppressive microenvironment and activating pro-tumorigenic signaling. These findings highlight TIPARP as a promising candidate for precision medicine and combination immunotherapy in PAAD.

Keywords

Immunity; Mendelian randomization; Pancreatic ductal adenocarcinoma; Prognostic biomarker; TIPARP.

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