Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma
Abstract Background Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensur...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-023-02877-w |
| _version_ | 1797451033247481856 |
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| author | Yibei Wang Ziwei Miao Xiaoxue Qin Yi Yang Si Wu Qi Miao Beibei Li Mingyu Zhang Pengfei Wu Yun Han Bo Li |
| author_facet | Yibei Wang Ziwei Miao Xiaoxue Qin Yi Yang Si Wu Qi Miao Beibei Li Mingyu Zhang Pengfei Wu Yun Han Bo Li |
| author_sort | Yibei Wang |
| collection | DOAJ |
| description | Abstract Background Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings. |
| first_indexed | 2024-03-09T14:49:07Z |
| format | Article |
| id | doaj.art-2e03724729f844da9b7adf4225f4c316 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-03-09T14:49:07Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-2e03724729f844da9b7adf4225f4c3162023-11-26T14:34:32ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662023-11-0142111910.1186/s13046-023-02877-wTranscriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinomaYibei Wang0Ziwei Miao1Xiaoxue Qin2Yi Yang3Si Wu4Qi Miao5Beibei Li6Mingyu Zhang7Pengfei Wu8Yun Han9Bo Li10Department of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical UniversityDepartment of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical UniversityDepartment of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical UniversityDepartment of Laboratory Animals, China Medical UniversityDepartment of Biobank, Shengjing Hospital of China Medical UniversityDepartment of Radiology, The First Hospital of China Medical UniversityDepartment of Radiology, Shengjing Hospital of China Medical UniversityDepartment of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical UniversityDepartment of Neurosurgery, The First Hospital of China Medical UniversityDepartment of Thoracic Surgery, Shengjing Hospital of China Medical UniversityDepartment of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical UniversityAbstract Background Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.https://doi.org/10.1186/s13046-023-02877-wEarly stage lung adenocarcinomaTranscriptome sequencingLipid raftsPhospholipid phosphatase 2Cell proliferation |
| spellingShingle | Yibei Wang Ziwei Miao Xiaoxue Qin Yi Yang Si Wu Qi Miao Beibei Li Mingyu Zhang Pengfei Wu Yun Han Bo Li Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma Journal of Experimental & Clinical Cancer Research Early stage lung adenocarcinoma Transcriptome sequencing Lipid rafts Phospholipid phosphatase 2 Cell proliferation |
| title | Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma |
| title_full | Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma |
| title_fullStr | Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma |
| title_full_unstemmed | Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma |
| title_short | Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma |
| title_sort | transcriptomic landscape based on annotated clinical features reveals plpp2 involvement in lipid raft mediated proliferation signature of early stage lung adenocarcinoma |
| topic | Early stage lung adenocarcinoma Transcriptome sequencing Lipid rafts Phospholipid phosphatase 2 Cell proliferation |
| url | https://doi.org/10.1186/s13046-023-02877-w |
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