Supplementary Material for: Prognostic Value of Pre- and Postoperative Anti-p53 Antibody Levels in Colorectal Cancer Patients: A Retrospective Study

<p><b><i>Objective:</i></b> To determine the utility of the post-/preoperative anti-p53 antibody (p53 Ab) ratio as a prognostic factor for colorectal cancer (CRC) recurrence. <b><i>Methods:</i></b> A total of 737 nonmetastatic CRC patients who had undergone R0 resection were retrospectively analyzed. p53 Ab levels were measured within 1 month prior to and at least every 3 months after surgery. Post-/preoperative p53 Ab ratios were calculated, and the optimal ratio cutoff values for predicting recurrence were determined using the Kaplan-Meier method and the log-rank test. <b><i>Results:</i></b> Preoperative p53 Ab elevation was observed in 194 patients (pre-p53 high). Preoperative p53 Ab levels correlated with TNM stage. Re-elevation of p53 Ab levels occurred on recurrence in the pre-p53 high group, but not in the pre-p53 low group (n = 543). In the pre-p53 high group, patients who experienced tumor recurrence exhibited a slow postoperative reduction of p53 Ab levels, and a post-/preoperative p53 Ab ratio >0.4 at postoperative 3 months predicted relapse-free survival. In other words, a p53 Ab level remaining higher than 40% of the preoperative level was an independent and strong risk factor for recurrence in multivariate analyses. <b><i>Conclusion:</i></b> In CRC patients with preoperative p53 Ab elevation, the rate of p53 Ab reduction in the early postsurgical period is a promising prognostic factor for recurrence.</p

Supplementary Material for: Genome-wide analysis of DNA methylation in pseudomyxoma peritonei originated from appendiceal neoplasms

Introduction: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remain unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. Methods: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight non-cancerous colonic epithelial cells using Methylation EPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. Results: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. Conclusions: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease