CD74 is a potential biomarker predicting the response to immune checkpoint blockade
Abstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation...
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| Format: | Article |
| Language: | English |
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BMC
2024-10-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03524-w |
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| author | Wen-Qi Shi Dan-Xun Chen Ze-Sen Du Chun-Peng Liu Tian-Tian Zhai Feng Pan Hai-Lu Chen Wei-Nan Liao Shao-Hong Wang Jun-Hui Fu Si-Qi Qiu Zhi-Yong Wu |
| author_facet | Wen-Qi Shi Dan-Xun Chen Ze-Sen Du Chun-Peng Liu Tian-Tian Zhai Feng Pan Hai-Lu Chen Wei-Nan Liao Shao-Hong Wang Jun-Hui Fu Si-Qi Qiu Zhi-Yong Wu |
| author_sort | Wen-Qi Shi |
| collection | DOAJ |
| description | Abstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. Methods The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. Results In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. Conclusions The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB. |
| format | Article |
| id | doaj-art-163e9eee5dac44ce8b960c7d71031893 |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-163e9eee5dac44ce8b960c7d710318932025-08-20T01:50:39ZengBMCCancer Cell International1475-28672024-10-0124111310.1186/s12935-024-03524-wCD74 is a potential biomarker predicting the response to immune checkpoint blockadeWen-Qi Shi0Dan-Xun Chen1Ze-Sen Du2Chun-Peng Liu3Tian-Tian Zhai4Feng Pan5Hai-Lu Chen6Wei-Nan Liao7Shao-Hong Wang8Jun-Hui Fu9Si-Qi Qiu10Zhi-Yong Wu11Clinical Research Center, Shantou Central HospitalDiagnosis and Treatment Center of Breast Diseases, Shantou Central HospitalDepartment of Surgical Oncology, Shantou Central HospitalDepartment of Pathology, Shantou Central HospitalDepartment of Radiation Oncology, Cancer Hospital of Shantou University Medical CollegeClinical Research Center, Shantou Central HospitalDiagnosis and Treatment Center of Breast Diseases, Shantou Central HospitalDepartment of Surgical Oncology, Shantou Central HospitalDepartment of Pathology, Shantou Central HospitalDepartment of Surgical Oncology, Shantou Central HospitalClinical Research Center, Shantou Central HospitalClinical Research Center, Shantou Central HospitalAbstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. Methods The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. Results In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. Conclusions The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.https://doi.org/10.1186/s12935-024-03524-wImmunotherapyCD74Treatment responseBiomarker |
| spellingShingle | Wen-Qi Shi Dan-Xun Chen Ze-Sen Du Chun-Peng Liu Tian-Tian Zhai Feng Pan Hai-Lu Chen Wei-Nan Liao Shao-Hong Wang Jun-Hui Fu Si-Qi Qiu Zhi-Yong Wu CD74 is a potential biomarker predicting the response to immune checkpoint blockade Cancer Cell International Immunotherapy CD74 Treatment response Biomarker |
| title | CD74 is a potential biomarker predicting the response to immune checkpoint blockade |
| title_full | CD74 is a potential biomarker predicting the response to immune checkpoint blockade |
| title_fullStr | CD74 is a potential biomarker predicting the response to immune checkpoint blockade |
| title_full_unstemmed | CD74 is a potential biomarker predicting the response to immune checkpoint blockade |
| title_short | CD74 is a potential biomarker predicting the response to immune checkpoint blockade |
| title_sort | cd74 is a potential biomarker predicting the response to immune checkpoint blockade |
| topic | Immunotherapy CD74 Treatment response Biomarker |
| url | https://doi.org/10.1186/s12935-024-03524-w |
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