APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer
The accumulating evidence demonstrates that the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC), DNA-editing protein plays an important role in the molecular pathogenesis of cancer. In particular, the APOBEC3 family was shown to induce tumor mutations by an aberrant DNA edit...
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/12/2827 |
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| author | Honghong Guo Ling Zhu Lu Huang Zhen Sun Hui Zhang Baoting Nong Yuanyan Xiong |
| author_facet | Honghong Guo Ling Zhu Lu Huang Zhen Sun Hui Zhang Baoting Nong Yuanyan Xiong |
| author_sort | Honghong Guo |
| collection | DOAJ |
| description | The accumulating evidence demonstrates that the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC), DNA-editing protein plays an important role in the molecular pathogenesis of cancer. In particular, the APOBEC3 family was shown to induce tumor mutations by an aberrant DNA editing mechanism. However, knowledge regarding the reconstitution of the APOBEC family genes across cancer types is still lacking. Here, we systematically analyzed the molecular alterations, immuno-oncological features, and clinical relevance of the APOBEC family in pan-cancer. We found that APOBEC genes were widely and significantly differentially expressed between normal and cancer samples in 16 cancer types, and that their expression levels are significantly correlated with the prognostic value in 17 cancer types. Moreover, two patterns of APOBEC-mediated stratification with distinct immune characteristics were identified in different cancer types, respectively. In ACC, for example, the first pattern of APOBEC-mediated stratification was closely correlated with the phenotype of immune activation, which was characterized by a high immune score, increased infiltration of CD8 T cells, and higher survival. The other pattern of APOBEC-mediated stratification was closely correlated with the low-infiltration immune phenotype, which was characterized by a low immune score, lack of effective immune infiltration, and poorer survival. Further, we found the APOBEC-mediated pattern with low-infiltration immune was also highly associated with the advanced tumor subtype and the CIMP-high tumor subtype (CpG island hypermethylation). Patients with the APOBEC-mediated pattern with immune activation were more likely to have therapeutic advantages in ICB (immunological checkpoint blockade) treatment. Overall, our results provide a valuable resource that will be useful in guiding oncologic and therapeutic analyses of the role of APOBEC family in cancer. |
| first_indexed | 2024-03-10T00:14:34Z |
| format | Article |
| id | doaj.art-fd92cdfdfc684beba6a03345f00677d2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:14:34Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fd92cdfdfc684beba6a03345f00677d22023-11-23T15:54:51ZengMDPI AGCancers2072-66942022-06-011412282710.3390/cancers14122827APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-CancerHonghong Guo0Ling Zhu1Lu Huang2Zhen Sun3Hui Zhang4Baoting Nong5Yuanyan Xiong6Key Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaKey Laboratory of Gene Engineering, Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, ChinaThe accumulating evidence demonstrates that the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC), DNA-editing protein plays an important role in the molecular pathogenesis of cancer. In particular, the APOBEC3 family was shown to induce tumor mutations by an aberrant DNA editing mechanism. However, knowledge regarding the reconstitution of the APOBEC family genes across cancer types is still lacking. Here, we systematically analyzed the molecular alterations, immuno-oncological features, and clinical relevance of the APOBEC family in pan-cancer. We found that APOBEC genes were widely and significantly differentially expressed between normal and cancer samples in 16 cancer types, and that their expression levels are significantly correlated with the prognostic value in 17 cancer types. Moreover, two patterns of APOBEC-mediated stratification with distinct immune characteristics were identified in different cancer types, respectively. In ACC, for example, the first pattern of APOBEC-mediated stratification was closely correlated with the phenotype of immune activation, which was characterized by a high immune score, increased infiltration of CD8 T cells, and higher survival. The other pattern of APOBEC-mediated stratification was closely correlated with the low-infiltration immune phenotype, which was characterized by a low immune score, lack of effective immune infiltration, and poorer survival. Further, we found the APOBEC-mediated pattern with low-infiltration immune was also highly associated with the advanced tumor subtype and the CIMP-high tumor subtype (CpG island hypermethylation). Patients with the APOBEC-mediated pattern with immune activation were more likely to have therapeutic advantages in ICB (immunological checkpoint blockade) treatment. Overall, our results provide a valuable resource that will be useful in guiding oncologic and therapeutic analyses of the role of APOBEC family in cancer.https://www.mdpi.com/2072-6694/14/12/2827APOBECpan-cancergenetic alterationstumor microenvironmentsurvivalimmunotherapy |
| spellingShingle | Honghong Guo Ling Zhu Lu Huang Zhen Sun Hui Zhang Baoting Nong Yuanyan Xiong APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer Cancers APOBEC pan-cancer genetic alterations tumor microenvironment survival immunotherapy |
| title | APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer |
| title_full | APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer |
| title_fullStr | APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer |
| title_full_unstemmed | APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer |
| title_short | APOBEC Alteration Contributes to Tumor Growth and Immune Escape in Pan-Cancer |
| title_sort | apobec alteration contributes to tumor growth and immune escape in pan cancer |
| topic | APOBEC pan-cancer genetic alterations tumor microenvironment survival immunotherapy |
| url | https://www.mdpi.com/2072-6694/14/12/2827 |
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