MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment
MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immun...
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MDPI AG
2025-07-01
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| Series: | Current Oncology |
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| author | Qianqian Xue Yue Wang Qiang Zheng Ziling Huang Yicong Lin Yan Jin Yuan Li |
| author_facet | Qianqian Xue Yue Wang Qiang Zheng Ziling Huang Yicong Lin Yan Jin Yuan Li |
| author_sort | Qianqian Xue |
| collection | DOAJ |
| description | MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on formalin-fixed paraffin-embedded (FFPE) tissue samples from nine NSCLC patients, including four recurrent/metastatic and five non-recurrent/non-metastatic patients. Two panels assessed immune cell markers (CD8, CD4, CD20, CD68, and FoxP3) and immune checkpoints (PD-L1, LAG3, and TIM3). Immune cell infiltration and checkpoint expression were analyzed using HALO<sup>TM</sup> software (version 3.6.4134.464). Nearest neighbor analysis was conducted to assess the proximity of immune cells to tumor cells. Univariate Cox regression analysis assessed factors associated with disease-free survival (DFS). CD8+TIM3+ and CD8+LAG3+ cells were predominantly located in the tumor parenchyma of recurrent/metastatic patients but localized to the stroma in non-recurrent/non-metastatic patients. Non-recurrent/non-metastatic patients exhibited a higher density of tertiary lymphoid structures and closer proximity of CD20+ B cells, CD8+TIM3+, and CD8+LAG3+ cells to tumor cells compared to recurrent/metastatic patients, though the differences were not statistically significant. Cox regression analysis suggested a potential association between higher densities of CD8+TIM3+ cells and improved DFS (HR = 0.89), though these findings did not reach statistical significance. Our findings suggest that differences in immune microenvironmental factors, particularly those related to immune checkpoint expression (TIM3 and LAG3), may influence clinical outcomes in NSCLC patients with MET exon 14 skipping mutations. Further studies are needed to validate these observations and explore potential therapeutic implications. |
| format | Article |
| id | doaj-art-b1b0a75fd4584e75b01cdd28a2796d03 |
| institution | Matheson Library |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj-art-b1b0a75fd4584e75b01cdd28a2796d032025-07-25T13:19:26ZengMDPI AGCurrent Oncology1198-00521718-77292025-07-0132740310.3390/curroncol32070403MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune MicroenvironmentQianqian Xue0Yue Wang1Qiang Zheng2Ziling Huang3Yicong Lin4Yan Jin5Yuan Li6Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaMET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on formalin-fixed paraffin-embedded (FFPE) tissue samples from nine NSCLC patients, including four recurrent/metastatic and five non-recurrent/non-metastatic patients. Two panels assessed immune cell markers (CD8, CD4, CD20, CD68, and FoxP3) and immune checkpoints (PD-L1, LAG3, and TIM3). Immune cell infiltration and checkpoint expression were analyzed using HALO<sup>TM</sup> software (version 3.6.4134.464). Nearest neighbor analysis was conducted to assess the proximity of immune cells to tumor cells. Univariate Cox regression analysis assessed factors associated with disease-free survival (DFS). CD8+TIM3+ and CD8+LAG3+ cells were predominantly located in the tumor parenchyma of recurrent/metastatic patients but localized to the stroma in non-recurrent/non-metastatic patients. Non-recurrent/non-metastatic patients exhibited a higher density of tertiary lymphoid structures and closer proximity of CD20+ B cells, CD8+TIM3+, and CD8+LAG3+ cells to tumor cells compared to recurrent/metastatic patients, though the differences were not statistically significant. Cox regression analysis suggested a potential association between higher densities of CD8+TIM3+ cells and improved DFS (HR = 0.89), though these findings did not reach statistical significance. Our findings suggest that differences in immune microenvironmental factors, particularly those related to immune checkpoint expression (TIM3 and LAG3), may influence clinical outcomes in NSCLC patients with MET exon 14 skipping mutations. Further studies are needed to validate these observations and explore potential therapeutic implications.https://www.mdpi.com/1718-7729/32/7/403MET exon 14 skipping mutationnon-small-cell lung cancerimmune checkpointsimmune microenvironmentmultiplex immunofluorescence |
| spellingShingle | Qianqian Xue Yue Wang Qiang Zheng Ziling Huang Yicong Lin Yan Jin Yuan Li MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment Current Oncology MET exon 14 skipping mutation non-small-cell lung cancer immune checkpoints immune microenvironment multiplex immunofluorescence |
| title | MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment |
| title_full | MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment |
| title_fullStr | MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment |
| title_full_unstemmed | MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment |
| title_short | MET Exon 14 Skipping Mutations in Lung Cancer: Clinical–Pathological Characteristics and Immune Microenvironment |
| title_sort | met exon 14 skipping mutations in lung cancer clinical pathological characteristics and immune microenvironment |
| topic | MET exon 14 skipping mutation non-small-cell lung cancer immune checkpoints immune microenvironment multiplex immunofluorescence |
| url | https://www.mdpi.com/1718-7729/32/7/403 |
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