SPDL1 is associated with prognosis and tumor proliferation in pancreatic adenocarcinoma.

purposePancreatic cancer (PAAD), an aggressive digestive malignancy with high mortality, has limited advanced therapeutic options, underscoring the need for novel biomarkers and targets. SPDL1, linked to tumor cell dysregulation and aberrantly expressed in PAAD, has an uncharacterized mechanism. This study investigates its function and underlying mechanism.

methodsThe expression pattern of SPDL1 in PAAD tissues was interrogated utilizing data derived from the TCGA and GEO database. Immunohistochemistry (IHC) was then performed to validate the bioinformatically obtained findings. Additionally, single-cell RNA sequencing datasets pertaining to PAAD were retrieved from the Tumor Immune Single-cell Hub database and subjected to subsequent bioinformatic analysis. The correlation between SPDL1 expression and clinical parameters, its prognostic impact, and independent prognostic factors were evaluated via TCGA, the Kaplan-Meier plotter, and univariate/multivariate Cox analyses, respectively. Nomograms were constructed based on independent prognostic factors and validated using the C-index, calibration curves, ROC curves, decision curve analysis, the net reclassification index (NRI), and the integrated discrimination index (IDI). GSEA and GSVA were performed to explore SPDL1’s underlying molecular mechanisms. Following SPDL1 silencing, its effects on PAAD cell proliferation and invasion were examined via CCK-8, colony formation, wound healing, EdU, and Transwell assays. Western blot was used to detect the protein expression of SPDL1, AKT, p-AKT, mTOR and p-mTOR.

resultsIn PAAD tissues, the SPDL1 gene was significantly higher than that in the corresponding adjacent cancer tissues, with its expression predominantly localized to tumor cells. Notably, high SPDL1 expression is significantly associated with unfavorable outcomes in PAAD patients. Correlation analysis further revealed that the expression level of SPDL1 is positively correlated with tumor proliferation signature. Additionally, functional experiments demonstrated that knockdown of SPDL1 via interference technology remarkably impaired the proliferation and migration capabilities of PAAD cell lines (p < 0.05). Additionally, combined bioinformatics analyses and Western blot assays were performed, which revealed that SPDL1 plays an indispensable role in regulating the PI3K/AKT/mTOR signaling cascade.

conclusionSPDL1 is highly expressed in PAAD, and its overexpression is associated with poor clinical outcomes. Moreover, SPDL1 was found to enhance the proliferation, migration, and invasion capacities of PAAD cells through the PI3K/AKT/mTOR signaling pathway.