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DNA错配修复（MMR）基因在肺癌中的表达及其与不同临床病理参数的相关性。

DNA mismatch repair (MMR) genes expression in lung cancer and its correlation with different clinicopathologic parameters.

作者信息

Farrag Mayada Saad, Abdelwahab Heba Wagih, Abdellateef Amr, Anber Nahla, Ellayeh Mohamed Adel, Hussein Dalia Tawfeek, Eldesoky Ahmed Ramadan, Sheta Heba

机构信息

Pathology Department, Port Said Faculty of Medicine, Port Said University, Port Said, Egypt.

Chest Medicine Department, Mansoura Faculty of Medicine, Mansoura, Egypt.

出版信息

Sci Rep. 2025 Jan 6;15(1):885. doi: 10.1038/s41598-024-83067-2.

DOI:10.1038/s41598-024-83067-2
PMID:39762286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11704133/
Abstract

Lung cancer (LC) is a crucial rapidly developing disease. In Egypt, it is one of the five most frequent cancers. Little is known about the impact of deleted mismatch repair genes and its correlation to clinicopathological characteristics. This study evaluates immunohistochemical expression of the mismatch repair genes (PMS2), (MSH2), (MLH1) & (MSH6) & its correlation with clinicopathologic parameters & prognosis of LC. Age was higher with lost MLH1 & PMS2 but HTN was higher with lost four markers. Smoking was associated with expression of MLH1 & PMS2. A progressive course was associated with lost MSH2 & MSH6. Suprarenal metastasis was associated with lost all markers but bone metastasis was associated with lost MSH2 & MSH6. All the markers were significantly correlated with each other, with perfect correlations between MSH6 & MSH2 and between MLH & PMS2. Median overall survival among cases with lost markers was significantly lower than patients with preserved markers. We recommend evaluation of the four proteins as a biomarker that could guide LC therapy. In-depth biological research is imperative to elucidate the precise roles and mechanisms of these markers. This will advance management strategies and even guide immune checkpoint inhibitor therapy for LC.

摘要

肺癌（LC）是一种关键的快速发展的疾病。在埃及，它是最常见的五种癌症之一。关于错配修复基因缺失的影响及其与临床病理特征的相关性，人们了解甚少。本研究评估错配修复基因（PMS2）、（MSH2）、（MLH1）和（MSH6）的免疫组化表达及其与LC临床病理参数和预后的相关性。MLH1和PMS2缺失时年龄较大，但四种标志物缺失时高血压发生率较高。吸烟与MLH1和PMS2的表达有关。疾病进展与MSH2和MSH6缺失有关。肾上腺转移与所有标志物缺失有关，但骨转移与MSH2和MSH6缺失有关。所有标志物之间均显著相关，MSH6与MSH2之间以及MLH与PMS2之间呈完美相关。标志物缺失的病例的中位总生存期显著低于标志物保留的患者。我们建议评估这四种蛋白作为一种生物标志物，可指导LC治疗。深入的生物学研究对于阐明这些标志物的确切作用和机制至关重要。这将推进管理策略，甚至指导LC的免疫检查点抑制剂治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/4fea297cfbf1/41598_2024_83067_Fige_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/0db862660054/41598_2024_83067_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/b38de52c4810/41598_2024_83067_Figb_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/a4e7708c7b9e/41598_2024_83067_Figc_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/1424168bde32/41598_2024_83067_Figd_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/4fea297cfbf1/41598_2024_83067_Fige_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/0db862660054/41598_2024_83067_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/b38de52c4810/41598_2024_83067_Figb_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/a4e7708c7b9e/41598_2024_83067_Figc_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/1424168bde32/41598_2024_83067_Figd_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2682/11704133/4fea297cfbf1/41598_2024_83067_Fige_HTML.jpg

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本文引用的文献

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Somatic Mutations in Surgically Treated Colorectal Liver Metastases: An Overview.手术治疗的结直肠癌肝转移灶中的体细胞突变：概述。
Cells. 2024 Apr 14;13(8):679. doi: 10.3390/cells13080679.
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Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis.错配修复蛋白缺陷及其对结直肠癌远处转移的影响：一项综合分析。
Cancer Med. 2024 Apr;13(7):e6994. doi: 10.1002/cam4.6994.
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Microsatellite Instability and Mismatch Repair Deficiency Define a Distinct Subset of Lung Cancers Characterized by Smoking Exposure, High Tumor Mutational Burden, and Recurrent Somatic MLH1 Inactivation.微卫星不稳定性和错配修复缺陷定义了一类独特的肺癌亚型，其特征为有吸烟暴露史、肿瘤突变负荷高以及体细胞MLH1反复失活。
J Thorac Oncol. 2024 Mar;19(3):409-424. doi: 10.1016/j.jtho.2023.10.004. Epub 2023 Oct 12.
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Characterization of mismatch-repair/microsatellite instability-discordant endometrial cancers.错配修复/微卫星不稳定不一致型子宫内膜癌的特征。
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