Appendiceal Adenocarcinoma, Appendiceal Cancer
Conditions
Keywords
Appendiceal cancer, Appendiceal adenocarcinoma, DNA methylation, m6A modification, Multi-omics, MeRIP-seq, Histologic grade;, Epigenomics, Epitranscriptomics, Molecular subtype, Risk stratification, Prognostic biomarker
Brief summary
This study investigates integrated epigenetic and epitranscriptomic features of appendiceal cancer using archived tumor tissue specimens from the same patient cohort. The study includes DNA methylation profiling and m6A epitranscriptomic profiling to define molecular subtypes, evaluate associations with clinicopathologic features, and develop molecular risk scores for prognostic stratification. The primary goal is to determine whether DNA methylation- and m6A-based molecular features can complement conventional histopathologic grading and improve risk stratification.
Detailed description
Appendiceal cancer is a rare and heterogeneous malignancy with limited clinically actionable biomarkers for risk stratification. Histologic grade remains one of the strongest determinants of prognosis, but outcomes among patients with lower-grade disease remain variable. This study is designed to characterize the molecular architecture of appendiceal cancer through integrated analysis of DNA methylation and m6A epitranscriptomic profiles generated from archived tumor tissue specimens from the same patient cohort. The study uses formalin-fixed paraffin-embedded appendiceal cancer tissues, and where available benign or normal appendix tissues, together with matched clinicopathologic and follow-up data. DNA methylation profiling is performed to evaluate tumor-associated methylation patterns, identify differentially methylated regions or features, and assess their association with clinical and survival outcomes. In parallel, m6A epitranscriptomic profiling is performed using m6A-enriched RNA sequencing with matched input RNA sequencing to quantify transcriptome-wide m6A enrichment. Molecular data are analyzed to identify tumor-associated epigenetic and epitranscriptomic alterations, define molecular subtypes, and construct continuous molecular risk scores. These molecular features are evaluated in relation to histologic grade, histologic subtype, lymph node metastasis, lymphovascular invasion, perineural invasion, peritoneal cancer index, overall survival, and progression-free survival. The study aims to determine whether DNA methylation and m6A-based profiling can provide complementary molecular information for appendiceal cancer classification, prognostic modeling, and future biomarker development.
Interventions
DIAGNOSTIC_TESTDNA Methylation Profiling
Archived tissue specimens undergo DNA methylation profiling to characterize tumor-associated methylation alterations and identify methylation-based molecular features associated with clinicopathologic variables and survival outcomes. The profiling is performed for research purposes only and does not assign treatment.
DIAGNOSTIC_TESTm6A Epitranscriptomic Profiling
Archived tissue specimens undergo m6A methylated RNA immunoprecipitation sequencing with matched input RNA sequencing to quantify transcriptome-wide m6A enrichment. The resulting molecular data are used for subtype discovery, m6A score construction, reduced-panel development, and association with clinicopathologic and survival outcomes.
Sponsors
City of Hope Medical Center
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed appendiceal adenocarcinoma or appendiceal cancer. * Availability of archived tumor tissue suitable for molecular profiling. * Availability of tissue for DNA methylation profiling, m6A epitranscriptomic profiling, or both. * Availability of relevant clinicopathologic data. * Availability of survival or follow-up information when applicable. * Age 18 years or older at diagnosis or tissue collection.
Exclusion criteria
* Insufficient tissue quantity or quality for molecular profiling. * Inadequate DNA or RNA quality for sequencing or molecular assay preparation. * Missing essential clinicopathologic information required for analysis. * Non-appendiceal primary tumor or metastatic tumor to the appendix from another primary site. * Patients who do not meet institutional review board or consent requirements, if applicable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Through study completion, an average of 1 year | Overall survival will be evaluated in relation to molecular profiling results and available clinicopathologic characteristics. Survival analyses may include Kaplan-Meier analysis and Cox proportional hazards models |
| Progression-Free Survival | Through study completion, an average of 1 year | Progression-free survival will be evaluated in relation to molecular profiling results and available clinicopathologic characteristics. Time-to-event analyses may be performed using standard survival analysis methods. |
Countries
United States
Contacts
CONTACTAjay Goel
Outcome results
None listed