A 15-Inflammation-Related Gene Signature Predicts the Prognosis of Patients With Pancreatic Ductal Adenocarcinoma

Abstract

Chronic inflammation promotes the development of pancreatic ductal adenocarcinoma (PDAC) and PDAC-related inflammatory tumor microenvironment facilitates tumor growth and metastasis. Thus, we aimed to study the association between inflammatory response and prognosis in patients with PDAC. We conducted the whole transcriptomic sequencing using tissue samples collected from patients diagnosed with PDAC (n = 106) recruited from Shandong Cancer Hospital. We first constructed a prognostic signature using 15 inflammation-related genes in The Cancer Genome Atlas (TCGA) cohort (n = 177) and further validated it in an independent International Cancer Genome Consortium (ICGC) cohort (n = 90) and our in-house cohort. PDAC patients with a higher risk score had poorer overall survival (OS) (P < 0.001; HR, 3.02; 95% CI, 1.94-4.70). The association between the prognostic signature and OS remained significant in the multivariable Cox regression adjusting for age, sex, alcohol exposure, diabetes, and stage (P < 0.001; HR, 2.91; 95% CI, 1.73-4.89). This gene signature also robustly predicted prognosis in the ICGC cohort (P = 0.01; HR, 1.94; 95% CI, 1.14-3.30) and our cohort (P < 0.001; HR, 2.40; 95% CI, 1.45-3.97). Immune subtype C3 (inflammatory) was enriched and CD8⁺ T cells were higher in patients with a lower risk score (P < 0.05). Furthermore, PDAC patients with higher risk scores were more sensitive to chemotherapy, immunotherapy, and PARP inhibitors (P < 0.05). In sum, we identified a novel gene signature that was associated with inflammatory response for risk stratification, prognosis prediction, and therapy guidance in PDAC patients. Future studies are warranted to validate the clinical utility of the signature.

Keywords:

• Inflammation
• pancreatic ductal adenocarcinoma
• prognosis
• immune cells infiltration

Ethics approval and informed consent

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences (Approval No. SDZLEC2021-136). The written informed consents were obtained from all the participants.

Author contributions

Xiaofeng Sun: Investigation (lead); Methodology (equal); Visualization (equal); Writing-original draft (equal). Hao Song: Investigation (equal); Methodology (equal); Visualization (equal); Writing-original draft (equal). Xiaoran Sun: Investigation (supporting); Methodology (supporting); Writing-original draft (supporting). Chunhua Liao: Investigation (supporting); Visualization (supporting); Writing-original draft (supporting). Guoqiang Wang: Writing-original draft (supporting). Yu Xu: Writing-original draft (supporting). Leo Li: Writing-original draft (supporting). Yusheng Han: Writing-original draft (supporting); Funding acquisition (supporting). Chunwei Xu: Writing-original draft (supporting). Wenxian Wang: Writing-original draft (supporting). Shangli Cai: Writing-original draft (supporting). Hua Liang: Conceptualization (lead); Writing-original draft (supporting); Writing-review & editing (supporting). Hao Yu: Funding acquisition (lead); Conceptualization (lead); Writing-original draft (lead); Writing-review & editing (lead).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The relevant data supporting the findings of this study are available within the paper. Due to ethical and privacy concerns, we are unable to publish the patient-level data in our study, of which readers may contact the corresponding authors for the access for non-commercial purposes.

Additional information

Funding

This work was supported by the Shandong Medical and Health Technology Development Project (Grant No. 202105010436); and the 2018 Entrepreneurial Leading Talent of Guangzhou Huangpu District and Guangzhou Development District (Grant No. 2022-L023).