The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment
Abstract Background Metabolic pathways are known to significantly impact the development and advancement of lung cancer. This study sought to establish a signature related to butyrate metabolism that is specifically linked to lung adenocarcinoma (LUAD). Methods For the purpose of identifying butyrat...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-024-13409-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594651877474304 |
|---|---|
| author | Yanchao Luan Chao Liang Qingsong Han Xueqin Zhou Na Yang li Zhao |
| author_facet | Yanchao Luan Chao Liang Qingsong Han Xueqin Zhou Na Yang li Zhao |
| author_sort | Yanchao Luan |
| collection | DOAJ |
| description | Abstract Background Metabolic pathways are known to significantly impact the development and advancement of lung cancer. This study sought to establish a signature related to butyrate metabolism that is specifically linked to lung adenocarcinoma (LUAD). Methods For the purpose of identifying butyrate metabolism-related differentially expressed genes (BMR-DEGs) in the TCGA-LUAD dataset, we introduced transcriptome data. This was followed by the implementation of the univariate Cox and LASSO analyses in order to construct a LUAD gene signature. We performed a comprehensive analysis of gene function enrichment between the two populations at risk, thoroughly examined their immune microenvironment characteristics, and assessed the effectiveness of immunotherapy. Finally, the function of CDKN3 in LUAD was verified by in vitro experiments. Results Through a comprehensive analysis of the TCGA-LUAD dataset, 51 significant BMR-DEGs were confirmed. Subsequently, five characteristic genes, CPS1, ABCC2, CDKN3, SLC2A1, and IGFBP1 were identified to create prognostic features for butyrate metabolism related outcomes in LUAD. Cox regression analysis determined that the pathological T stage, tumor stage, and RiskScore could serve as independent prognostic indicators. Analysis of the abundance of 22 immune infiltrating cells revealed that 15 immune cell types exhibited substantial differences and were strongly associated with risk ratings and prognosis. An important correlation exists between risk ratings and immunological checkpoints, which can be utilized to forecast the efficacy of treatment. In the high-risk group, there was an upregulation of the expression of PD-L2, PD-L1, and PD-1. Additionally, the risk score showed a positive correlation with TIDE and Exclusion score, while showing a negative correlation with Dysfunction score. Furthermore, the IC50 values for cisplatin, paclitaxel, and docetaxel were notably elevated in the high-risk group, indicating that these medications could potentially provide therapeutic advantages for this particular group. Finally, we determined that knockdown CDKN3 inhibited the proliferation and metastasis of LUAD cells. Conclusion We identify and validate a novel BMR-related prognostic signature comprising 5 DEGs for LUAD patients. Our data might provide a new molecular target for LUAD treatment. |
| format | Article |
| id | doaj-art-cb2930bf0a264bf6ba8add71382280c3 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-cb2930bf0a264bf6ba8add71382280c32025-01-19T12:26:59ZengBMCBMC Cancer1471-24072025-01-0125111810.1186/s12885-024-13409-wThe systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatmentYanchao Luan0Chao Liang1Qingsong Han2Xueqin Zhou3Na Yang4li Zhao5Hebei Chest HospitalHebei Provincial Lung Cancer Prevention and Treatment Research CenterHebei Provincial Lung Cancer Prevention and Treatment Research CenterHebei Provincial Lung Cancer Prevention and Treatment Research CenterHebei Provincial Lung Cancer Prevention and Treatment Research CenterHebei Provincial Lung Cancer Prevention and Treatment Research CenterAbstract Background Metabolic pathways are known to significantly impact the development and advancement of lung cancer. This study sought to establish a signature related to butyrate metabolism that is specifically linked to lung adenocarcinoma (LUAD). Methods For the purpose of identifying butyrate metabolism-related differentially expressed genes (BMR-DEGs) in the TCGA-LUAD dataset, we introduced transcriptome data. This was followed by the implementation of the univariate Cox and LASSO analyses in order to construct a LUAD gene signature. We performed a comprehensive analysis of gene function enrichment between the two populations at risk, thoroughly examined their immune microenvironment characteristics, and assessed the effectiveness of immunotherapy. Finally, the function of CDKN3 in LUAD was verified by in vitro experiments. Results Through a comprehensive analysis of the TCGA-LUAD dataset, 51 significant BMR-DEGs were confirmed. Subsequently, five characteristic genes, CPS1, ABCC2, CDKN3, SLC2A1, and IGFBP1 were identified to create prognostic features for butyrate metabolism related outcomes in LUAD. Cox regression analysis determined that the pathological T stage, tumor stage, and RiskScore could serve as independent prognostic indicators. Analysis of the abundance of 22 immune infiltrating cells revealed that 15 immune cell types exhibited substantial differences and were strongly associated with risk ratings and prognosis. An important correlation exists between risk ratings and immunological checkpoints, which can be utilized to forecast the efficacy of treatment. In the high-risk group, there was an upregulation of the expression of PD-L2, PD-L1, and PD-1. Additionally, the risk score showed a positive correlation with TIDE and Exclusion score, while showing a negative correlation with Dysfunction score. Furthermore, the IC50 values for cisplatin, paclitaxel, and docetaxel were notably elevated in the high-risk group, indicating that these medications could potentially provide therapeutic advantages for this particular group. Finally, we determined that knockdown CDKN3 inhibited the proliferation and metastasis of LUAD cells. Conclusion We identify and validate a novel BMR-related prognostic signature comprising 5 DEGs for LUAD patients. Our data might provide a new molecular target for LUAD treatment.https://doi.org/10.1186/s12885-024-13409-wLung adenocarcinomaButyrate metabolismPrognostic signatureRisk subgroupsCDKN3 |
| spellingShingle | Yanchao Luan Chao Liang Qingsong Han Xueqin Zhou Na Yang li Zhao The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment BMC Cancer Lung adenocarcinoma Butyrate metabolism Prognostic signature Risk subgroups CDKN3 |
| title | The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| title_full | The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| title_fullStr | The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| title_full_unstemmed | The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| title_short | The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| title_sort | systematic analysis of genes related to butyrate metabolism suggests that cdkn3 could serve as a promising therapeutic target for lung adenocarcinoma treatment |
| topic | Lung adenocarcinoma Butyrate metabolism Prognostic signature Risk subgroups CDKN3 |
| url | https://doi.org/10.1186/s12885-024-13409-w |
| work_keys_str_mv | AT yanchaoluan thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT chaoliang thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT qingsonghan thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT xueqinzhou thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT nayang thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT lizhao thesystematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT yanchaoluan systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT chaoliang systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT qingsonghan systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT xueqinzhou systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT nayang systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment AT lizhao systematicanalysisofgenesrelatedtobutyratemetabolismsuggeststhatcdkn3couldserveasapromisingtherapeutictargetforlungadenocarcinomatreatment |