Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma
Abstract Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is predicted to encode a large type I transmembrane protein involved in hearing transmission and mediating cellular immunity under physiological conditions. However, its role in cancer progression, especially in lung adenocarc...
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Nature Portfolio
2025-01-01
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Online Access: | https://doi.org/10.1038/s41598-025-85981-5 |
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author | Xiangqian Zhang Jie Wang Hanyang Su Xiaojin Liu |
author_facet | Xiangqian Zhang Jie Wang Hanyang Su Xiaojin Liu |
author_sort | Xiangqian Zhang |
collection | DOAJ |
description | Abstract Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is predicted to encode a large type I transmembrane protein involved in hearing transmission and mediating cellular immunity under physiological conditions. However, its role in cancer progression, especially in lung adenocarcinoma (LUAD), has not been fully elucidated. In this study, we observed significantly lower expression of PKHD1L1 in LUAD tissues than in normal lung tissues on the basis of the integration of public datasets from the TCGA and GEO cohorts. Furthermore, we found that low PKHD1L1 expression was a strong predictor of poor prognosis in patients with LUAD. Pathway enrichment analyses revealed that PKHD1L1 is associated primarily with asthma and multiple immune processes. Through meticulous analysis of immune cell infiltrates and single-cell datasets, we discerned a notable correlation between the expression of PKHD1L1 and the presence of B cells, with a particularly strong association observed in plasma cells. This finding led us to believe that the role of PKHD1L1 may extend beyond its previously reported involvement in cellular immunity, potentially impacting humoral immunity as well. In vitro experiments revealed that the over-expression of PKHD1L1 significantly inhibited the proliferation and migration ability of LUAD cell lines. These findings suggest that PKHD1L1 is an important prognostic indicator and a potential therapeutic target for LUAD. |
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id | doaj-art-f837a29466064b94a6c53c20df3b2f14 |
institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-01-01 |
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spelling | doaj-art-f837a29466064b94a6c53c20df3b2f142025-01-26T12:25:06ZengNature PortfolioScientific Reports2045-23222025-01-0115111810.1038/s41598-025-85981-5Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinomaXiangqian Zhang0Jie Wang1Hanyang Su2Xiaojin Liu3Department of Oncology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South UniversityDepartment of Gastroenterology & National Clinical Research Centerfor Geriatric Disorders, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine & Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South UniversityDepartment of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South UniversityAbstract Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is predicted to encode a large type I transmembrane protein involved in hearing transmission and mediating cellular immunity under physiological conditions. However, its role in cancer progression, especially in lung adenocarcinoma (LUAD), has not been fully elucidated. In this study, we observed significantly lower expression of PKHD1L1 in LUAD tissues than in normal lung tissues on the basis of the integration of public datasets from the TCGA and GEO cohorts. Furthermore, we found that low PKHD1L1 expression was a strong predictor of poor prognosis in patients with LUAD. Pathway enrichment analyses revealed that PKHD1L1 is associated primarily with asthma and multiple immune processes. Through meticulous analysis of immune cell infiltrates and single-cell datasets, we discerned a notable correlation between the expression of PKHD1L1 and the presence of B cells, with a particularly strong association observed in plasma cells. This finding led us to believe that the role of PKHD1L1 may extend beyond its previously reported involvement in cellular immunity, potentially impacting humoral immunity as well. In vitro experiments revealed that the over-expression of PKHD1L1 significantly inhibited the proliferation and migration ability of LUAD cell lines. These findings suggest that PKHD1L1 is an important prognostic indicator and a potential therapeutic target for LUAD.https://doi.org/10.1038/s41598-025-85981-5PKHD1L1LUADImmunotherapy |
spellingShingle | Xiangqian Zhang Jie Wang Hanyang Su Xiaojin Liu Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma Scientific Reports PKHD1L1 LUAD Immunotherapy |
title | Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma |
title_full | Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma |
title_fullStr | Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma |
title_full_unstemmed | Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma |
title_short | Integrative analysis of single-cell and transcriptome sequencing with experimental validation reveals PKHD1L1 as a novel biomarker in lung adenocarcinoma |
title_sort | integrative analysis of single cell and transcriptome sequencing with experimental validation reveals pkhd1l1 as a novel biomarker in lung adenocarcinoma |
topic | PKHD1L1 LUAD Immunotherapy |
url | https://doi.org/10.1038/s41598-025-85981-5 |
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