Prognostic Factors of Pseudomyxoma Peritonei: TP53 and MUC16 Mutations as Potential Biomarkers

To evaluate prognostic factors of pseudomyxoma peritonei (PMP), both univariate and multivariate analysis were conducted. The results showed that gender was the only independent predictor among the clinical factors. Age, histopathologic subtype, peritoneal cancer index (PCI), completeness of cytoreduction (CC), and lymph node involvement were not significant indicators for overall survival or progression-free survival. In terms of genomic biomarkers, TP53 and MUC16 were identified as independent prognostic factors in PMP patients who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). TP53 is a well-known tumor suppressor gene that plays a critical role in various cancers by responding to cellular stresses and maintaining genomic integrity. MUC16, a member of the mucin (MUC) family, is a highly glycosylated macromolecule expressed in mammalian epithelial cells, contributing to the formation of mucous barriers and protection against infections. MUC16 has been widely recognized as a classical prognostic biomarker in ovarian cancer. It is worth noting that TP53 family genes interact with MUC16, potentially regulating mucinous molecular characteristics. We hypothesize that mutated MUC16 may contribute to the rupture of appendiceal mucosa, leading to the dissemination of mucus into the abdominal cavity, while loss-of-function events in TP53 gene result in MUC16 mutations. However, the poor prognosis associated with SMAD4 mutation, observed in the univariate analysis, did not persist in the multivariate model. This discrepancy may be attributed to the correlation between SMAD4 and TGFBR2, as both genes are involved in the TGFβ signaling pathway, which regulates various physiological processes such as angiogenesis, wound healing, immune suppression, and epithelial-to-mesenchymal transition (EMT). Our findings suggest that TP53 and MUC16 mutations could serve as biomarkers for predicting PMP prognosis, and the interaction between these two genes may promote PMP progression.