Abstract
Objective: Pancreatic adenocarcinoma (PAAD) is a common malignant tumor worldwide. S100 family (S100s) is wildly involved in regulating the occurrence, development, invasion, metastasis, apoptosis, and drug resistance of many malignant tumors. However, the expression pattern, prognostic value, and oncological role of individual S100s members in PAAD need to be elucidated. Methods: The transcriptional expression levels of S100s were analyzed through the Oncomine and GEPIA, respectively. The protein levels of S100s members in PAAD were studied by Human Protein Atlas. The correlation between S100 mRNA expression and overall survival and tumor stage in PAAD patients was studied by GEPIA. The transcriptional expression correlation and gene mutation rate of S100s members in PAAD patients were explored by cBioPortal. The co-expression networks of S100s are identified using STRING and Gene MANIA to predict their potential functions. The correlation of S100s expression and tumor-infiltrating immune cells was tested by TIMER. Pathway activity and drug target analyzed by GSCALite. Results: 13 S100s members were upregulated in PAAD tissues. 15 S100s members were associated with TP53 mutation. Expression levels of S100A3/A5/A6/A10/A11/A14/A16/B/P/Z were significantly correlated with the pathological stage. Prognosis analysis demonstrated that PAAD patients with low mRNA levels of S100A1/B/Z or high levels of S100A2/A3/A5/A10/A11/A14/A16 had a poor prognosis. Immuno-infiltration analysis showed that the mRNA levels of S100A10/A11/A14/A16 were correlated with the infiltration degree of macrophages in PAAD. Drug sensitivity analysis showed that PAAD expressing high levels of S100A2/A6/A10/A11/A13/A14/A16 maybe resistant to small molecule drugs. Conclusion: This study identifies the clinical significance and biological functions of the S100s in PAAD, which may provide novel insights for the selection of prognostic biomarkers.
Highlights
Pancreatic adenocarcinoma (PAAD) is a highly lethal disease and has become the seventh leading cause of cancer-related deaths, accounting for about 4.7% of global mortality (Sung et al, 2021)
Combined with the transcriptional expression profile, we concluded that high mRNA expression of S100A2/A3/A10/A11/A14/A16 was correlated with poor overall survival (OS), while high expression of S100B was related to better OS
These findings suggested that S100A2/A10/A11/A14/A16 may have the potential to become a biomarker for prognosis or treatment of PAAD
Summary
Pancreatic adenocarcinoma (PAAD) is a highly lethal disease and has become the seventh leading cause of cancer-related deaths, accounting for about 4.7% of global mortality (Sung et al, 2021). PAAD is associated with a very poor prognosis, with a 5-years survival rate of as low as 8% after diagnosis (Mishra et al, 2019). Great strides have been made on the screening, diagnosis and comprehensive therapy combining surgery, chemotherapy, and radiotherapy, PAAD remains a highly malignant tumor with limited treatment options (Kamisawa et al, 2016). Conventional treatments, such as surgery, have poor clinical outcomes, and only about 20% of patients benefiting from radical surgery (Lai et al, 2019). Seeking for key genes and proteins related to the occurrence, development, and metastasis of PAAD is of great significance in improving the prognosis
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