ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1605227
This article is part of the Research TopicPrecision Therapeutics in Rare Cancers: Targeting Tumor Microenvironment and Biomarker-Driven ApproachesView all 4 articles
Immune microenvironment heterogeneity characterizes biologically distinct KRAS mut /SPOP mut and KRAS mut /PIK3CA mut mesonephric-like adenocarcinoma subtypes revealed by integrated whole-exome and transcriptomic profiling
Provisionally accepted
Jing Zeng1,2
Qingli Li1,2
Kemin LI1,2
Lu Yang1,2
Lian Xu1,3Wei Wang1,3Kaixuan Yang1,3Qingbo Wei4Jing Wang4
Changbin Zhu4
Rutie Yin1,2*- 1Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China
- 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
- 3Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
- 4Amoy Diagnostics Co., Ltd., Xiamen, Fujian Province, China
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Objective: This study aims to uncover the molecular biology and immune microenvironment of gynecological mesonephric-like adenocarcinoma (MLA) .To determine the comprehensive characteristics of MLA, 17 patients with MLA were retrospectively enrolled in this study. Whole-exome sequencing and mRNA sequencing were performed to explore the molecular features. The biological differences between MLAs and epithelial-initiated gynecologic tumors reported in The Cancer Genome Atlas database were also analyzed.Results: KRAS mutations (82.4%) were considered the driving mechanism and were co-mutated with PIK3CA (47.1%) and SPOP (23.5%), but their functions were mutually exclusive. In addition, pathways and genes associated with kidney development were upregulated in MLA patients.Compared with adjacent tissues and common gynecological tumors in The Cancer Genome Atlas, Th2 signature and resting mast cells account for the majority in MLAs, rendering an immunosuppressive TME. Particularly, the expression leves of IFNG, IFN6, and IFN1 KRAS_SPOP group, significantly lower than the rates found in KRAS_PIK3CA group. KRAS_SPOP mutant MLAs, exhibited reduced immune infiltration in their tumor microenvironment.This is the first study to demonstrate the comprehensive molecular characteristics of MLA and detect biologically distinct subtypes of KRAS mut /SPOP mut and KRAS mut /PIK3CA mut MLAs.
Keywords: Mesonephric-like adenocarcinoma, immune microenvironment, Molecular Biology, whole-exome, transcriptomic profiling Gynecological mesonephric-like adenocarcinoma, kidney development, Tumor Microenvironment, KRAS
Received: 03 Apr 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Zeng, Li, LI, Yang, Xu, Wang, Yang, Wei, Wang, Zhu and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rutie Yin, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China
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