The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy
Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is...
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MDPI AG
2022-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/6/902 |
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| author | Hsiao-Chen Lee Chao-Yuan Chang Kuan-Li Wu Hung-Hsing Chiang Yung-Yun Chang Lian-Xiu Liu Yung-Chi Huang Jen-Yu Hung Ya-Ling Hsu Yu-Yuan Wu Ying-Ming Tsai |
| author_facet | Hsiao-Chen Lee Chao-Yuan Chang Kuan-Li Wu Hung-Hsing Chiang Yung-Yun Chang Lian-Xiu Liu Yung-Chi Huang Jen-Yu Hung Ya-Ling Hsu Yu-Yuan Wu Ying-Ming Tsai |
| author_sort | Hsiao-Chen Lee |
| collection | DOAJ |
| description | Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies. |
| first_indexed | 2024-03-09T23:20:40Z |
| format | Article |
| id | doaj.art-9097c2a0a70441a8b1199424b33483fd |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T23:20:40Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-9097c2a0a70441a8b1199424b33483fd2023-11-23T17:27:20ZengMDPI AGJournal of Personalized Medicine2075-44262022-05-0112690210.3390/jpm12060902The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable TherapyHsiao-Chen Lee0Chao-Yuan Chang1Kuan-Li Wu2Hung-Hsing Chiang3Yung-Yun Chang4Lian-Xiu Liu5Yung-Chi Huang6Jen-Yu Hung7Ya-Ling Hsu8Yu-Yuan Wu9Ying-Ming Tsai10Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanLung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.https://www.mdpi.com/2075-4426/12/6/902ADAMTS8EGFRGATA1NKTlung cancerTreg |
| spellingShingle | Hsiao-Chen Lee Chao-Yuan Chang Kuan-Li Wu Hung-Hsing Chiang Yung-Yun Chang Lian-Xiu Liu Yung-Chi Huang Jen-Yu Hung Ya-Ling Hsu Yu-Yuan Wu Ying-Ming Tsai The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy Journal of Personalized Medicine ADAMTS8 EGFR GATA1 NKT lung cancer Treg |
| title | The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy |
| title_full | The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy |
| title_fullStr | The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy |
| title_full_unstemmed | The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy |
| title_short | The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy |
| title_sort | therapeutic potential of adamts8 in lung adenocarcinoma without targetable therapy |
| topic | ADAMTS8 EGFR GATA1 NKT lung cancer Treg |
| url | https://www.mdpi.com/2075-4426/12/6/902 |
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