Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer
Aldo-keto reductase family 1 member C3 (AKR1C3) plays an important role in prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It is necessary to establish a genetic signature associated with AKR1C3 that can be used to predict the prognosis of PCa patients...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4513 |
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| author | Xiaoli Cui Changcheng Li Jipeng Ding Zhou Yao Tianyu Zhao Jiahui Guo Yaru Wang Jing Li |
| author_facet | Xiaoli Cui Changcheng Li Jipeng Ding Zhou Yao Tianyu Zhao Jiahui Guo Yaru Wang Jing Li |
| author_sort | Xiaoli Cui |
| collection | DOAJ |
| description | Aldo-keto reductase family 1 member C3 (AKR1C3) plays an important role in prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It is necessary to establish a genetic signature associated with AKR1C3 that can be used to predict the prognosis of PCa patients and provide important information for clinical treatment decisions. AKR1C3-related genes were identified via label-free quantitative proteomics of the AKR1C3-overexpressing LNCaP cell line. A risk model was constructed through the analysis of clinical data, PPI, and Cox-selected risk genes. Cox regression analysis, Kaplan–Meier (K–M) curves, and receiver operating characteristic (ROC) curves were used to verify the accuracy of the model, and two external datasets were used to verify the reliability of the results. Subsequently, the tumor microenvironment and drug sensitivity were explored. Moreover, the roles of AKR1C3 in the progression of PCa were verified in LNCaP cells. MTT, colony formation, and EdU assays were conducted to explore cell proliferation and drug sensitivity to enzalutamide. Migration and invasion abilities were measured using wound-healing and transwell assays, and qPCR was used to assess the expression levels of AR target genes and EMT genes. CDC20, SRSF3, UQCRH, INCENP, TIMM10, TIMM13, POLR2L, and NDUFAB1 were identified as AKR1C3-associated risk genes. These risk genes, established using the prognostic model, can effectively predict the recurrence status, immune microenvironment, and drug sensitivity of PCa. Tumor-infiltrating lymphocytes and several immune checkpoints that promote cancer progression were higher in high-risk groups. Furthermore, there was a close correlation between the sensitivity of PCa patients to bicalutamide and docetaxel and the expression levels of the eight risk genes. Moreover, through in vitro experiments, Western blotting confirmed that AKR1C3 enhanced SRSF3, CDC20, and INCENP expression. We found that PCa cells with a high expression of AKR1C3 have high proliferation ability and high migration ability and were insensitive to enzalutamide. AKR1C3-associated genes had a significant role in the process of PCa, immune responses, and drug sensitivity and offer the potential for a novel model for prognostic prediction in PCa. |
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| issn | 1661-6596 1422-0067 |
| language | English |
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| spelling | doaj.art-773bd67712db4b3ba6fb912f76f495e42023-11-17T07:49:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245451310.3390/ijms24054513Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate CancerXiaoli Cui0Changcheng Li1Jipeng Ding2Zhou Yao3Tianyu Zhao4Jiahui Guo5Yaru Wang6Jing Li7Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaAldo-keto reductase family 1 member C3 (AKR1C3) plays an important role in prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It is necessary to establish a genetic signature associated with AKR1C3 that can be used to predict the prognosis of PCa patients and provide important information for clinical treatment decisions. AKR1C3-related genes were identified via label-free quantitative proteomics of the AKR1C3-overexpressing LNCaP cell line. A risk model was constructed through the analysis of clinical data, PPI, and Cox-selected risk genes. Cox regression analysis, Kaplan–Meier (K–M) curves, and receiver operating characteristic (ROC) curves were used to verify the accuracy of the model, and two external datasets were used to verify the reliability of the results. Subsequently, the tumor microenvironment and drug sensitivity were explored. Moreover, the roles of AKR1C3 in the progression of PCa were verified in LNCaP cells. MTT, colony formation, and EdU assays were conducted to explore cell proliferation and drug sensitivity to enzalutamide. Migration and invasion abilities were measured using wound-healing and transwell assays, and qPCR was used to assess the expression levels of AR target genes and EMT genes. CDC20, SRSF3, UQCRH, INCENP, TIMM10, TIMM13, POLR2L, and NDUFAB1 were identified as AKR1C3-associated risk genes. These risk genes, established using the prognostic model, can effectively predict the recurrence status, immune microenvironment, and drug sensitivity of PCa. Tumor-infiltrating lymphocytes and several immune checkpoints that promote cancer progression were higher in high-risk groups. Furthermore, there was a close correlation between the sensitivity of PCa patients to bicalutamide and docetaxel and the expression levels of the eight risk genes. Moreover, through in vitro experiments, Western blotting confirmed that AKR1C3 enhanced SRSF3, CDC20, and INCENP expression. We found that PCa cells with a high expression of AKR1C3 have high proliferation ability and high migration ability and were insensitive to enzalutamide. AKR1C3-associated genes had a significant role in the process of PCa, immune responses, and drug sensitivity and offer the potential for a novel model for prognostic prediction in PCa.https://www.mdpi.com/1422-0067/24/5/4513prostate cancerAKR1C3bioinformaticslabel-free quantitative proteomics |
| spellingShingle | Xiaoli Cui Changcheng Li Jipeng Ding Zhou Yao Tianyu Zhao Jiahui Guo Yaru Wang Jing Li Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer International Journal of Molecular Sciences prostate cancer AKR1C3 bioinformatics label-free quantitative proteomics |
| title | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer |
| title_full | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer |
| title_fullStr | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer |
| title_full_unstemmed | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer |
| title_short | Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer |
| title_sort | establishing a proteomics based signature of akr1c3 related genes for predicting the prognosis of prostate cancer |
| topic | prostate cancer AKR1C3 bioinformatics label-free quantitative proteomics |
| url | https://www.mdpi.com/1422-0067/24/5/4513 |
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