Diagnosis and prognosis of pancreatic cancer with immunoglobulin heavy constant delta blood marker

J Cancer Res Clin Oncol. 2023 Nov;149(14):12977-12992. doi: 10.1007/s00432-023-05161-8. Epub 2023 Jul 19.

Abstract

Background: Pancreatic cancer (PC) is highly malignant and difficult to detect, while few blood markers are currently available for diagnosing PC.

Methods: We obtained differential expression genes (DEGs) from GEO (gene expression omnibus) database and assessed by quantitative real-time polymerase chain reaction (qRT-PCR), receiver operating characteristic (ROC), univariate and multifactorial regression analysis, and survival analysis in our clinic center. Through the TCGA (the cancer genome atlas) database, we analyzed functional enrichment, different risk groups with survival analysis, immunological features, and the risk score established by the Cox regression model and constructed a nomogram.

Result: Immunoglobulin heavy constant delta (IGHD) was remarkably upregulated in peripheral blood from PC patients, and IGHD was a potential independent biomarker for PC diagnosis (ROC sensitivity, 76.0%; specificity, 74.2%; area under the curve (AUC) = 0.817; univariate logistic regression analysis: odds ratio (OR) 1.488; 95% confidence interval (CI) 1.182-1.872; P < 0.001; multiple logistic: OR 2.097; 95% CI 1.276-3.389, P = 0.003). In addition, the IGHD expression was remarkably reduced after resectioning the primary tumor. High IGHD expression indicated higher lymphocyte infiltration and increased activities of immunological pathways in PC patients. KRAS and SMAD were observed with a prominent difference among top mutated genes between the two groups. The risk score predicted reliable clinical prognosis and drug responses. Furthermore, a nomogram with the risk score and clinical characteristics was constructed, showing a better predictive performance.

Conclusion: IGHD is a valuable PC diagnosis, prognosis, and therapeutic response marker.

Keywords: Biomarker; Blood; Diagnosis; IGHD; Pancreatic cancer; Prognosis.