Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma
Abstract Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12890-023-02770-4 |
| _version_ | 1797340329365471232 |
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| author | He Tian Ran Wei Chu Xiao Tao Fan Yun Che Tiejun Liu Bo Zheng Chunxiang Li Jie He |
| author_facet | He Tian Ran Wei Chu Xiao Tao Fan Yun Che Tiejun Liu Bo Zheng Chunxiang Li Jie He |
| author_sort | He Tian |
| collection | DOAJ |
| description | Abstract Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients’ poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC. |
| first_indexed | 2024-03-08T10:01:30Z |
| format | Article |
| id | doaj.art-1d4d24951dca4eb8961edd4d14f927e0 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-03-08T10:01:30Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-1d4d24951dca4eb8961edd4d14f927e02024-01-29T10:54:56ZengBMCBMC Pulmonary Medicine1471-24662024-01-0124111510.1186/s12890-023-02770-4Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinomaHe Tian0Ran Wei1Chu Xiao2Tao Fan3Yun Che4Tiejun Liu5Bo Zheng6Chunxiang Li7Jie He8Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAbstract Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients’ poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.https://doi.org/10.1186/s12890-023-02770-4KLK8Squamous cell lung carcinoma (LUSC)PrognosisTumor immune microenvironment (TIME)Biomarker |
| spellingShingle | He Tian Ran Wei Chu Xiao Tao Fan Yun Che Tiejun Liu Bo Zheng Chunxiang Li Jie He Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma BMC Pulmonary Medicine KLK8 Squamous cell lung carcinoma (LUSC) Prognosis Tumor immune microenvironment (TIME) Biomarker |
| title | Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma |
| title_full | Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma |
| title_fullStr | Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma |
| title_full_unstemmed | Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma |
| title_short | Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma |
| title_sort | tumor derived klk8 predicts inferior survival and promotes an immune suppressive tumor microenvironment in lung squamous cell carcinoma |
| topic | KLK8 Squamous cell lung carcinoma (LUSC) Prognosis Tumor immune microenvironment (TIME) Biomarker |
| url | https://doi.org/10.1186/s12890-023-02770-4 |
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