Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma
Oncogene-induced senescence occurs following oncogene activation in normal cells and is considered as a critical tumor-suppressing mechanism. Ubiquitin-specific protease 10 (USP10) has been reported to play a vital role in oncogene-induced senescence via the deubiquitination-dependent stabilization...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-10-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428318808678 |
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| author | Joon Seon Song Joo Mi Yi Hanbyoul Cho Chel Hun Choi Yoonho Park Eun Joo Chung Jaewhan Song Joon-Yong Chung Seung-Mo Hong |
| author_facet | Joon Seon Song Joo Mi Yi Hanbyoul Cho Chel Hun Choi Yoonho Park Eun Joo Chung Jaewhan Song Joon-Yong Chung Seung-Mo Hong |
| author_sort | Joon Seon Song |
| collection | DOAJ |
| description | Oncogene-induced senescence occurs following oncogene activation in normal cells and is considered as a critical tumor-suppressing mechanism. Ubiquitin-specific protease 10 (USP10) has been reported to play a vital role in oncogene-induced senescence via the deubiquitination-dependent stabilization of p14ARF. However, knowledge of the clinical significance of USP10 and p14ARF expression in patients with small intestinal adenocarcinoma is limited. To study the clinical significance of USP10 and p14ARF expression, we performed immunohistochemistry for USP10 and p14ARF on 195 surgically resected small intestinal adenocarcinoma specimens. Furthermore, we performed methylation analysis on five small intestinal adenocarcinoma samples and matched adjacent normal intestinal tissue samples. UPS10 ( p = 0.023) and p14ARF ( p = 0.007) expression were significantly decreased in adenocarcinoma in comparison with normal tissue. The loss of USP10 was observed in 124/194 (63.9%) of small intestinal adenocarcinoma samples and was correlated with a higher pT stage ( p = 0.044), lymphatic invasion ( p = 0.033), and the absence of sporadic adenoma ( p = 0.024) and peritumoral dysplasia ( p = 0.019). p14ARF expression was downregulated in 75/195 (38.5%) of small intestinal adenocarcinoma samples and was associated with vascular ( p = 0.011) and lymphatic ( p = 0.013) invasions. The loss of USP10 expression was associated with the loss of p14ARF expression ( r = 0.342, p < 0.001). Multivariate survival analysis revealed that the combined loss of USP10 and p14ARF expression could be an independent prognostic factor for overall survival in small intestinal adenocarcinoma. Furthermore, the aberrant hypermethylation of the USP10 and p14ARF promoter could be a key mechanism for the downregulation of USP10 and p14ARF proteins in small intestinal adenocarcinoma. These findings suggest that the dual loss of USP10 and p14ARF could be used as a prognostic indicator of small intestinal adenocarcinoma. |
| format | Article |
| id | doaj-art-ea6319b26c6e466e86a13a37ace252bb |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2018-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-ea6319b26c6e466e86a13a37ace252bb2025-08-20T03:57:54ZengSAGE PublishingTumor Biology1423-03802018-10-014010.1177/1010428318808678Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinomaJoon Seon Song0Joo Mi Yi1Hanbyoul Cho2Chel Hun Choi3Yoonho Park4Eun Joo Chung5Jaewhan Song6Joon-Yong Chung7Seung-Mo Hong8Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of KoreaDepartment of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of KoreaDepartment of Obstetrics and Gynecology, Gangnam Severance Hospital, College of Medicine, Yonsei University, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaExperimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USARadiation Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institute of Health (NIH), Bethesda, MD, USADepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaExperimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USADepartment of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of KoreaOncogene-induced senescence occurs following oncogene activation in normal cells and is considered as a critical tumor-suppressing mechanism. Ubiquitin-specific protease 10 (USP10) has been reported to play a vital role in oncogene-induced senescence via the deubiquitination-dependent stabilization of p14ARF. However, knowledge of the clinical significance of USP10 and p14ARF expression in patients with small intestinal adenocarcinoma is limited. To study the clinical significance of USP10 and p14ARF expression, we performed immunohistochemistry for USP10 and p14ARF on 195 surgically resected small intestinal adenocarcinoma specimens. Furthermore, we performed methylation analysis on five small intestinal adenocarcinoma samples and matched adjacent normal intestinal tissue samples. UPS10 ( p = 0.023) and p14ARF ( p = 0.007) expression were significantly decreased in adenocarcinoma in comparison with normal tissue. The loss of USP10 was observed in 124/194 (63.9%) of small intestinal adenocarcinoma samples and was correlated with a higher pT stage ( p = 0.044), lymphatic invasion ( p = 0.033), and the absence of sporadic adenoma ( p = 0.024) and peritumoral dysplasia ( p = 0.019). p14ARF expression was downregulated in 75/195 (38.5%) of small intestinal adenocarcinoma samples and was associated with vascular ( p = 0.011) and lymphatic ( p = 0.013) invasions. The loss of USP10 expression was associated with the loss of p14ARF expression ( r = 0.342, p < 0.001). Multivariate survival analysis revealed that the combined loss of USP10 and p14ARF expression could be an independent prognostic factor for overall survival in small intestinal adenocarcinoma. Furthermore, the aberrant hypermethylation of the USP10 and p14ARF promoter could be a key mechanism for the downregulation of USP10 and p14ARF proteins in small intestinal adenocarcinoma. These findings suggest that the dual loss of USP10 and p14ARF could be used as a prognostic indicator of small intestinal adenocarcinoma.https://doi.org/10.1177/1010428318808678 |
| spellingShingle | Joon Seon Song Joo Mi Yi Hanbyoul Cho Chel Hun Choi Yoonho Park Eun Joo Chung Jaewhan Song Joon-Yong Chung Seung-Mo Hong Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma Tumor Biology |
| title | Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| title_full | Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| title_fullStr | Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| title_full_unstemmed | Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| title_short | Dual loss of USP10 and p14ARF protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| title_sort | dual loss of usp10 and p14arf protein expression is associated with poor prognosis in patients with small intestinal adenocarcinoma |
| url | https://doi.org/10.1177/1010428318808678 |
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