Copper-related genes predict prognosis and characteristics of breast cancer
BackgroundThe role of copper in cancer treatment is multifaceted, with copper homeostasis-related genes associated with both breast cancer prognosis and chemotherapy resistance. Interestingly, both elimination and overload of copper have been reported to have therapeutic potential in cancer treatmen...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145080/full |
| _version_ | 1797838643209961472 |
|---|---|
| author | Yi Liu Jiandong Wang Mengxi Jiang Mengxi Jiang |
| author_facet | Yi Liu Jiandong Wang Mengxi Jiang Mengxi Jiang |
| author_sort | Yi Liu |
| collection | DOAJ |
| description | BackgroundThe role of copper in cancer treatment is multifaceted, with copper homeostasis-related genes associated with both breast cancer prognosis and chemotherapy resistance. Interestingly, both elimination and overload of copper have been reported to have therapeutic potential in cancer treatment. Despite these findings, the exact relationship between copper homeostasis and cancer development remains unclear, and further investigation is needed to clarify this complexity.MethodsThe pan-cancer gene expression and immune infiltration analysis were performed using the Cancer Genome Atlas Program (TCGA) dataset. The R software packages were employed to analyze the expression and mutation status of breast cancer samples. After constructing a prognosis model to separate breast cancer samples by LASSO-Cox regression, we examined the immune statement, survival status, drug sensitivity and metabolic characteristics of the high- and low-copper related genes scoring groups. We also studied the expression of the constructed genes using the human protein atlas database and analyzed their related pathways. Finally, copper staining was performed with the clinical sample to investigate the distribution of copper in breast cancer tissue and paracancerous tissue.ResultsPan-cancer analysis showed that copper-related genes are associated with breast cancer, and the immune infiltration profile of breast cancer samples is significantly different from that of other cancers. The essential copper-related genes of LASSO-Cox regression were ATP7B (ATPase Copper Transporting Beta) and DLAT (Dihydrolipoamide S-Acetyltransferase), whose associated genes were enriched in the cell cycle pathway. The low-copper related genes scoring group presented higher levels of immune activation, better probabilities of survival, enrichment in pathways related to pyruvate metabolism and apoptosis, and higher sensitivity to chemotherapy drugs. Immunohistochemistry staining showed high protein expression of ATP7B and DLAT in breast cancer samples. The copper staining showed copper distribution in breast cancer tissue.ConclusionThis study displayed the potential impacts of copper-related genes on the overall survival, immune infiltration, drug sensitivity and metabolic profile of breast cancer, which could predict patients’ survival and tumor statement. These findings may serve to support future research efforts aiming at improving the management of breast cancer. |
| first_indexed | 2024-04-09T15:45:14Z |
| format | Article |
| id | doaj.art-68a5c14e3c2e45239a9eba9745d2917c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T15:45:14Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-68a5c14e3c2e45239a9eba9745d2917c2023-04-27T04:47:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11450801145080Copper-related genes predict prognosis and characteristics of breast cancerYi Liu0Jiandong Wang1Mengxi Jiang2Mengxi Jiang3Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaAdvanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, ChinaBackgroundThe role of copper in cancer treatment is multifaceted, with copper homeostasis-related genes associated with both breast cancer prognosis and chemotherapy resistance. Interestingly, both elimination and overload of copper have been reported to have therapeutic potential in cancer treatment. Despite these findings, the exact relationship between copper homeostasis and cancer development remains unclear, and further investigation is needed to clarify this complexity.MethodsThe pan-cancer gene expression and immune infiltration analysis were performed using the Cancer Genome Atlas Program (TCGA) dataset. The R software packages were employed to analyze the expression and mutation status of breast cancer samples. After constructing a prognosis model to separate breast cancer samples by LASSO-Cox regression, we examined the immune statement, survival status, drug sensitivity and metabolic characteristics of the high- and low-copper related genes scoring groups. We also studied the expression of the constructed genes using the human protein atlas database and analyzed their related pathways. Finally, copper staining was performed with the clinical sample to investigate the distribution of copper in breast cancer tissue and paracancerous tissue.ResultsPan-cancer analysis showed that copper-related genes are associated with breast cancer, and the immune infiltration profile of breast cancer samples is significantly different from that of other cancers. The essential copper-related genes of LASSO-Cox regression were ATP7B (ATPase Copper Transporting Beta) and DLAT (Dihydrolipoamide S-Acetyltransferase), whose associated genes were enriched in the cell cycle pathway. The low-copper related genes scoring group presented higher levels of immune activation, better probabilities of survival, enrichment in pathways related to pyruvate metabolism and apoptosis, and higher sensitivity to chemotherapy drugs. Immunohistochemistry staining showed high protein expression of ATP7B and DLAT in breast cancer samples. The copper staining showed copper distribution in breast cancer tissue.ConclusionThis study displayed the potential impacts of copper-related genes on the overall survival, immune infiltration, drug sensitivity and metabolic profile of breast cancer, which could predict patients’ survival and tumor statement. These findings may serve to support future research efforts aiming at improving the management of breast cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145080/fullbreast cancercopper metabolismcuproptosisprognosischaracteristics |
| spellingShingle | Yi Liu Jiandong Wang Mengxi Jiang Mengxi Jiang Copper-related genes predict prognosis and characteristics of breast cancer Frontiers in Immunology breast cancer copper metabolism cuproptosis prognosis characteristics |
| title | Copper-related genes predict prognosis and characteristics of breast cancer |
| title_full | Copper-related genes predict prognosis and characteristics of breast cancer |
| title_fullStr | Copper-related genes predict prognosis and characteristics of breast cancer |
| title_full_unstemmed | Copper-related genes predict prognosis and characteristics of breast cancer |
| title_short | Copper-related genes predict prognosis and characteristics of breast cancer |
| title_sort | copper related genes predict prognosis and characteristics of breast cancer |
| topic | breast cancer copper metabolism cuproptosis prognosis characteristics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1145080/full |
| work_keys_str_mv | AT yiliu copperrelatedgenespredictprognosisandcharacteristicsofbreastcancer AT jiandongwang copperrelatedgenespredictprognosisandcharacteristicsofbreastcancer AT mengxijiang copperrelatedgenespredictprognosisandcharacteristicsofbreastcancer AT mengxijiang copperrelatedgenespredictprognosisandcharacteristicsofbreastcancer |