Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization
<b>Background:</b> Previously, we found that an uncharacterized protein CXorf38 is significantly downregulated in human ZIP8-knockout (KO) cells. Given that ZIP8 regulates essential micronutrients linked to diseases including cancer, this study aims to characterize CXorf38 and evaluate i...
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2025-06-01
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| author | Rui Yan Heng-Wee Tan Na-Li Cai Le Yu Yan Gao Yan-Ming Xu Andy T. Y. Lau |
| author_facet | Rui Yan Heng-Wee Tan Na-Li Cai Le Yu Yan Gao Yan-Ming Xu Andy T. Y. Lau |
| author_sort | Rui Yan |
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| description | <b>Background:</b> Previously, we found that an uncharacterized protein CXorf38 is significantly downregulated in human ZIP8-knockout (KO) cells. Given that ZIP8 regulates essential micronutrients linked to diseases including cancer, this study aims to characterize CXorf38 and evaluate its role in lung adenocarcinoma. <b>Methods:</b> iTRAQ-based proteomics was previously used to identify the abundance of proteins in ZIP8-KO cells. Cell proliferation and colony formation assays were used to examine the function of CXorf38 by overexpressing the gene in lung adenocarcinoma cell lines. Kaplan–Meier survival analysis was used to assess the prognostic value of <i>CXorf38</i>, while TCGA clinical database analysis was used to evaluate its expression in lung cancer tissues, particularly in smokers. Bioinformatics analyses (GO, KEGG, PPI, and ICI) were performed on <i>CXorf38</i>-coexpressed genes derived from patients with lung cancer. <b>Results:</b> CXorf38 overexpression suppressed lung cancer cell proliferation and colony formation, suggesting a tumor-suppressive role. Higher <i>CXorf38</i> expression correlated with improved survival in patients with lung adenocarcinoma, but not in lung squamous cell carcinoma. Clinical data showed <i>CXorf38</i> downregulation with lung cancer tissues of smokers, indicating a potential role in smoking-induced cancer progression and treatment. Functional analysis using bioinformatics linked CXorf38 to immune response regulation, suggesting involvement in the tumor immune microenvironment. <b>Conclusions:</b> Our study reveals for the first time that CXorf38 is a potential tumor suppressor, prognostic biomarker, and/or tumor immune regulator in lung adenocarcinoma—further research is warranted to explore its role in tumor immunity and its therapeutic potential. |
| format | Article |
| id | doaj-art-a040a360cd114b8eb60af008708b9044 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Proteomes |
| spelling | doaj-art-a040a360cd114b8eb60af008708b90442025-08-20T03:27:32ZengMDPI AGProteomes2227-73822025-06-011322210.3390/proteomes13020022Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First CharacterizationRui Yan0Heng-Wee Tan1Na-Li Cai2Le Yu3Yan Gao4Yan-Ming Xu5Andy T. Y. Lau6The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, ChinaThe Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, ChinaLaboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, ChinaLaboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, ChinaThe Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, ChinaLaboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, ChinaThe Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China<b>Background:</b> Previously, we found that an uncharacterized protein CXorf38 is significantly downregulated in human ZIP8-knockout (KO) cells. Given that ZIP8 regulates essential micronutrients linked to diseases including cancer, this study aims to characterize CXorf38 and evaluate its role in lung adenocarcinoma. <b>Methods:</b> iTRAQ-based proteomics was previously used to identify the abundance of proteins in ZIP8-KO cells. Cell proliferation and colony formation assays were used to examine the function of CXorf38 by overexpressing the gene in lung adenocarcinoma cell lines. Kaplan–Meier survival analysis was used to assess the prognostic value of <i>CXorf38</i>, while TCGA clinical database analysis was used to evaluate its expression in lung cancer tissues, particularly in smokers. Bioinformatics analyses (GO, KEGG, PPI, and ICI) were performed on <i>CXorf38</i>-coexpressed genes derived from patients with lung cancer. <b>Results:</b> CXorf38 overexpression suppressed lung cancer cell proliferation and colony formation, suggesting a tumor-suppressive role. Higher <i>CXorf38</i> expression correlated with improved survival in patients with lung adenocarcinoma, but not in lung squamous cell carcinoma. Clinical data showed <i>CXorf38</i> downregulation with lung cancer tissues of smokers, indicating a potential role in smoking-induced cancer progression and treatment. Functional analysis using bioinformatics linked CXorf38 to immune response regulation, suggesting involvement in the tumor immune microenvironment. <b>Conclusions:</b> Our study reveals for the first time that CXorf38 is a potential tumor suppressor, prognostic biomarker, and/or tumor immune regulator in lung adenocarcinoma—further research is warranted to explore its role in tumor immunity and its therapeutic potential.https://www.mdpi.com/2227-7382/13/2/22CXorf38lung cancerORF proteinuncharacterized protein |
| spellingShingle | Rui Yan Heng-Wee Tan Na-Li Cai Le Yu Yan Gao Yan-Ming Xu Andy T. Y. Lau Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization Proteomes CXorf38 lung cancer ORF protein uncharacterized protein |
| title | Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization |
| title_full | Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization |
| title_fullStr | Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization |
| title_full_unstemmed | Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization |
| title_short | Chromosome X Open Reading Frame 38 (CXorf38) Is a Tumor Suppressor and Potential Prognostic Biomarker in Lung Adenocarcinoma: The First Characterization |
| title_sort | chromosome x open reading frame 38 cxorf38 is a tumor suppressor and potential prognostic biomarker in lung adenocarcinoma the first characterization |
| topic | CXorf38 lung cancer ORF protein uncharacterized protein |
| url | https://www.mdpi.com/2227-7382/13/2/22 |
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