PROGNOSTIC IMPACT OF MOLECULAR PROFILES AND MOLECULAR SIGNATURES IN CLEAR CELL OVARIAN CANCER

Main Article Content

Naheed Akhtar
Amna Najam
Sadia Kanwal
Jaweria Faisal
Wania Afzal
Jaisingh Rajput

Keywords

Ovarian Clear Cell Carcinoma (OCCC), Mutational Signatures, ARID1A, PIK3CA, Tumor Mutational Burden (TMB)

Abstract

Introduction: Ovarian Clear Cell Carcinoma (OCCC) presents a complex molecular landscape necessitating a thorough investigation. Our study aimed to elucidate molecular profiles and mutational signatures in OCCC, utilizing innovative methods such as Next Generation Sequencing (NGS) and introducing novel subgrouping based on mutational signatures.


Methodology: A carefully selected cohort of 150 OCCC patients underwent meticulous data collection, including clinical demographics, pathological characteristics, and treatment history. NGS techniques identified mutations in key genes (e.g., ARID1A, PIK3CA) within relevant pathways. Mutational analysis encompassed detailed sequencing parameters, and distinct molecular subgroups were identified using cluster analysis techniques.


Resuts: ARID1A mutations were prevalent in 45% of cases, PIK3CA mutations in 35%, and a noteworthy co-occurrence in 25%. Additional mutations within crucial pathways provided a nuanced molecular profile. Molecular subgrouping revealed four distinct groups characterized by unique mutational signatures, shedding light on C-APOBEC enzyme activation and AGEING. Calculation of Tumor Mutational Burden (TMB) yielded a median of 8.5 mutations per megabase. TMB emerged as a promising prognostic tool, with elevated TMB associated with adverse clinical outcomes. Kaplan-Meier survival curves and Cox proportional hazards models further validated the prognostic significance of TMB in OCCC. Chi-square tests highlighted specific mutations correlating with clinical parameters, while subgroup analyses demonstrated varied prognostic implications based on mutational profiles.


Conclusion: Our research study advances our understanding of OCCC's molecular complexity, introducing TMB as a prognostic marker and unveiling distinct molecular subgroups. These findings underscore the importance of personalized treatment strategies and warrant further exploration for their clinical relevance and impact on patient outcomes.

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