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SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer
Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized m...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910917/ https://www.ncbi.nlm.nih.gov/pubmed/35269894 http://dx.doi.org/10.3390/ijms23052753 |
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author | Sugimura-Nagata, Akane Koshino, Akira Nagao, Kazuhiro Nagano, Aya Komura, Masayuki Ueki, Akane Ebi, Masahide Ogasawara, Naotaka Tsuzuki, Toyonori Kasai, Kenji Takahashi, Satoru Kasugai, Kunio Inaguma, Shingo |
author_facet | Sugimura-Nagata, Akane Koshino, Akira Nagao, Kazuhiro Nagano, Aya Komura, Masayuki Ueki, Akane Ebi, Masahide Ogasawara, Naotaka Tsuzuki, Toyonori Kasai, Kenji Takahashi, Satoru Kasugai, Kunio Inaguma, Shingo |
author_sort | Sugimura-Nagata, Akane |
collection | PubMed |
description | Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients. |
format | Online Article Text |
id | pubmed-8910917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89109172022-03-11 SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer Sugimura-Nagata, Akane Koshino, Akira Nagao, Kazuhiro Nagano, Aya Komura, Masayuki Ueki, Akane Ebi, Masahide Ogasawara, Naotaka Tsuzuki, Toyonori Kasai, Kenji Takahashi, Satoru Kasugai, Kunio Inaguma, Shingo Int J Mol Sci Article Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients. MDPI 2022-03-02 /pmc/articles/PMC8910917/ /pubmed/35269894 http://dx.doi.org/10.3390/ijms23052753 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sugimura-Nagata, Akane Koshino, Akira Nagao, Kazuhiro Nagano, Aya Komura, Masayuki Ueki, Akane Ebi, Masahide Ogasawara, Naotaka Tsuzuki, Toyonori Kasai, Kenji Takahashi, Satoru Kasugai, Kunio Inaguma, Shingo SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title | SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title_full | SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title_fullStr | SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title_full_unstemmed | SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title_short | SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer |
title_sort | spata18 expression predicts favorable clinical outcome in colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910917/ https://www.ncbi.nlm.nih.gov/pubmed/35269894 http://dx.doi.org/10.3390/ijms23052753 |
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