Pan-Cancer Analysis of PAPPA Gene Reveals Tumor-Specific Prognostic Effects

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase regulating insulin-like growth factor (IGF) availability.
• The precise role of PAPPA in cancer progression and prognosis is not fully understood.

Purpose of the Study:

• To systematically investigate PAPPA expression, prognostic significance, cellular localization, and stromal associations across diverse cancer types.
• To clarify PAPPA's independent prognostic value compared to cancer-associated fibroblast (CAF) infiltration.

Main Methods:

• Integrated analysis of public datasets to examine PAPPA expression patterns.
• Assessment of PAPPA's correlation with overall survival and CAF infiltration markers.
• Multivariable Cox regression and pathway analyses.

Main Results:

• PAPPA expression varied across cancers, being reduced in some and elevated in cholangiocarcinoma and thyroid carcinoma.
• High PAPPA expression correlated with poorer survival in several cancers (bladder, cervical, lung squamous, mesothelioma, pancreatic, gastric) but was protective in lower-grade glioma.
• PAPPA often correlated with CAF infiltration in adverse prognostic tumors, but PAPPA remained an independent prognostic factor, while CAF infiltration often did not.

Conclusions:

• PAPPA is an independent prognostic factor in a majority of cancers studied.
• PAPPA expression frequently coincides with CAF infiltration, suggesting complex interactions.
• Further research is warranted to elucidate PAPPA's multifaceted role in cancer biology.