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Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer
BACKGROUND: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044481/ https://www.ncbi.nlm.nih.gov/pubmed/33889504 http://dx.doi.org/10.21037/tlcr-20-1027 |
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author | Lim, Jun Hyeok Oh, Sekyung Kim, Lucia Suh, Young Ju Ha, Yu-Jin Kim, Jung Soo Kim, Hyun-Jung Park, Mi Hwa Kim, Young Sam Cho, Yunjung Kwak, Seung Min Lee, Hong Lyeol Kim, You-Sun Ryu, Jeong-Seon |
author_facet | Lim, Jun Hyeok Oh, Sekyung Kim, Lucia Suh, Young Ju Ha, Yu-Jin Kim, Jung Soo Kim, Hyun-Jung Park, Mi Hwa Kim, Young Sam Cho, Yunjung Kwak, Seung Min Lee, Hong Lyeol Kim, You-Sun Ryu, Jeong-Seon |
author_sort | Lim, Jun Hyeok |
collection | PubMed |
description | BACKGROUND: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers. METHODS: We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death. RESULTS: We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes. CONCLUSIONS: Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype. |
format | Online Article Text |
id | pubmed-8044481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-80444812021-04-21 Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer Lim, Jun Hyeok Oh, Sekyung Kim, Lucia Suh, Young Ju Ha, Yu-Jin Kim, Jung Soo Kim, Hyun-Jung Park, Mi Hwa Kim, Young Sam Cho, Yunjung Kwak, Seung Min Lee, Hong Lyeol Kim, You-Sun Ryu, Jeong-Seon Transl Lung Cancer Res Original Article BACKGROUND: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers. METHODS: We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death. RESULTS: We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes. CONCLUSIONS: Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype. AME Publishing Company 2021-03 /pmc/articles/PMC8044481/ /pubmed/33889504 http://dx.doi.org/10.21037/tlcr-20-1027 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Lim, Jun Hyeok Oh, Sekyung Kim, Lucia Suh, Young Ju Ha, Yu-Jin Kim, Jung Soo Kim, Hyun-Jung Park, Mi Hwa Kim, Young Sam Cho, Yunjung Kwak, Seung Min Lee, Hong Lyeol Kim, You-Sun Ryu, Jeong-Seon Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title | Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title_full | Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title_fullStr | Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title_full_unstemmed | Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title_short | Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
title_sort | low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044481/ https://www.ncbi.nlm.nih.gov/pubmed/33889504 http://dx.doi.org/10.21037/tlcr-20-1027 |
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