Comprehensive Analysis of Co-Mutations in the PAPPA2 Gene in four Different Squamous Cell Carcinoma Types

INTRODUCTION: The PAPPA2 mutation is one of the oncogenic mutations that interact with other cancer-causing mutations to promote tumour formation. Studying the presence of co-mutations in PAPPA2 gene could provide valuable prognostic and predictive information to help improve the therapeutic management of cancer treatment.In our study,we examined the co-mutation patterns of PAPPA2 in LUSC, HNSCC, ESCC and CSCC.
METHODS: Mutation data for LUSC, HNSC, ESCC, and CSCC were obtained from The Cancer Genome Atlas via cBioPortal. Data were analyzed using R (v4.4.3). For each cancer type, the 20 most frequently mutated genes were identified, and their co-occurrence with PAPPA2 was evaluated using Fisher’s Exact Test (p < 0.05). Mutation landscapes were visualized using oncoprint plots.
RESULTS: In LUSC,PAPPA2 mutations (18%) significantly co-occurred with SPTA1, RYR2, and TTN. Additional associations were found with LRP1B, MUC16, PKHD1, RYR3, and USH2A. In HNSC, PAPPA2 alterations (8%) showed strong co-occurrence with NSD1, PKHD1L1, and TP53, as well as with FLG, SYNE1, and CSMD3. In ESCC, PAPPA2 mutations (8%) co-occurred significantly with FMN2 and NFE2L2. In CSCC, PAPPA2 mutations (29%) exhibited extensive co-occurrence with DNAH5, USH2A, and APOB, along with several structural genes including COL11A1, HMCN1, and FAT4.No significant mutually exclusive relationships were identified in any cancer type.Oncoprint analyses demonstrated diverse mutation spectra, primarily composed of missense and multi-hit events.
DISCUSSION AND CONCLUSION: A better understanding of co-mutational profiles is crucial for improving oncology strategies and personalising treatment for SCC patients.The findings may be able to improve cancer prognosis and treatment if they are put into practice in a clinical setting.

Keywords: PAPPA2 mutations, Co-mutation analysis, TCGA, Cancer genomics.