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Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma
BACKGROUND: We previously reported preoperative radiological morphology (RM) as an independent predictor for pathological upstaging after partial nephrectomy in patients with T1 renal cell carcinoma (RCC). PURPOSE: To investigate the prognostic importance of RM in all stages and the molecular charac...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773190/ https://www.ncbi.nlm.nih.gov/pubmed/36568232 http://dx.doi.org/10.3389/fonc.2022.1039383 |
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author | Kobatake, Kohei Ikeda, Kenichiro Teishima, Jun Sekino, Yohei Babasaki, Takashi Kohada, Yuki Tasaka, Ryo Takemoto, Kenshiro Fukushima, Takafumi Miyamoto, Shunsuke Kitano, Hiroyuki Goto, Keisuke Hieda, Keisuke Hayashi, Tetsutaro Hinata, Nobuyuki |
author_facet | Kobatake, Kohei Ikeda, Kenichiro Teishima, Jun Sekino, Yohei Babasaki, Takashi Kohada, Yuki Tasaka, Ryo Takemoto, Kenshiro Fukushima, Takafumi Miyamoto, Shunsuke Kitano, Hiroyuki Goto, Keisuke Hieda, Keisuke Hayashi, Tetsutaro Hinata, Nobuyuki |
author_sort | Kobatake, Kohei |
collection | PubMed |
description | BACKGROUND: We previously reported preoperative radiological morphology (RM) as an independent predictor for pathological upstaging after partial nephrectomy in patients with T1 renal cell carcinoma (RCC). PURPOSE: To investigate the prognostic importance of RM in all stages and the molecular characteristics underlying the differences between each type of RM in patients with clear cell RCC (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: The Cancer Imaging Archive datasets (TCIA), comprising CT images and RNA-sequencing data, were used (n = 163). Specimens from 63 patients with ccRCC at our institution and their CT images were used. All images were divided into three types according to RM classification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome were analyzed using Cox regression analysis and log-rank test. RESULTS AND LIMITATIONS: The irregular type was a significant independent predictor of worse disease-free survival (odds ratio: 2.22, p = 0.037) compared to round and lobular types in TCIA datasets. The irregular type showed a significant increase in both mRNA and protein expression of proteasome components, PSMB1 and PSMB3. Moreover, high expression of their coding genes shortened the progression-free survival of the patients with ccRCC who received sunitinib or avelumab plus axitinib therapy. The study limitations include the qualitative classification of RM and the need for novel radiomics and texture analysis techniques. CONCLUSIONS: Investigating RM on pre-treatment CT scans can effectively predict worse prognosis. Increased RM complexity may indirectly predict drug sensitivity via increased expression of PSMB1 and PSMB3 in patients with ccRCC. Specific targeting of the ubiquitin-proteasome system might be a novel treatment strategy for ccRCC with increased RM complexity. PATIENT SUMMARY: The clinical and morphological characteristics of patients with ccRCC vary greatly according to cancer staging. In this study, we built upon our prior findings of the prognostic importance of RM in T1 RCC and expanded it to encompass all stages of RCC, using a series of patients from a Japanese hospital. |
format | Online Article Text |
id | pubmed-9773190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97731902022-12-23 Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma Kobatake, Kohei Ikeda, Kenichiro Teishima, Jun Sekino, Yohei Babasaki, Takashi Kohada, Yuki Tasaka, Ryo Takemoto, Kenshiro Fukushima, Takafumi Miyamoto, Shunsuke Kitano, Hiroyuki Goto, Keisuke Hieda, Keisuke Hayashi, Tetsutaro Hinata, Nobuyuki Front Oncol Oncology BACKGROUND: We previously reported preoperative radiological morphology (RM) as an independent predictor for pathological upstaging after partial nephrectomy in patients with T1 renal cell carcinoma (RCC). PURPOSE: To investigate the prognostic importance of RM in all stages and the molecular characteristics underlying the differences between each type of RM in patients with clear cell RCC (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: The Cancer Imaging Archive datasets (TCIA), comprising CT images and RNA-sequencing data, were used (n = 163). Specimens from 63 patients with ccRCC at our institution and their CT images were used. All images were divided into three types according to RM classification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome were analyzed using Cox regression analysis and log-rank test. RESULTS AND LIMITATIONS: The irregular type was a significant independent predictor of worse disease-free survival (odds ratio: 2.22, p = 0.037) compared to round and lobular types in TCIA datasets. The irregular type showed a significant increase in both mRNA and protein expression of proteasome components, PSMB1 and PSMB3. Moreover, high expression of their coding genes shortened the progression-free survival of the patients with ccRCC who received sunitinib or avelumab plus axitinib therapy. The study limitations include the qualitative classification of RM and the need for novel radiomics and texture analysis techniques. CONCLUSIONS: Investigating RM on pre-treatment CT scans can effectively predict worse prognosis. Increased RM complexity may indirectly predict drug sensitivity via increased expression of PSMB1 and PSMB3 in patients with ccRCC. Specific targeting of the ubiquitin-proteasome system might be a novel treatment strategy for ccRCC with increased RM complexity. PATIENT SUMMARY: The clinical and morphological characteristics of patients with ccRCC vary greatly according to cancer staging. In this study, we built upon our prior findings of the prognostic importance of RM in T1 RCC and expanded it to encompass all stages of RCC, using a series of patients from a Japanese hospital. Frontiers Media S.A. 2022-12-08 /pmc/articles/PMC9773190/ /pubmed/36568232 http://dx.doi.org/10.3389/fonc.2022.1039383 Text en Copyright © 2022 Kobatake, Ikeda, Teishima, Sekino, Babasaki, Kohada, Tasaka, Takemoto, Fukushima, Miyamoto, Kitano, Goto, Hieda, Hayashi and Hinata https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Kobatake, Kohei Ikeda, Kenichiro Teishima, Jun Sekino, Yohei Babasaki, Takashi Kohada, Yuki Tasaka, Ryo Takemoto, Kenshiro Fukushima, Takafumi Miyamoto, Shunsuke Kitano, Hiroyuki Goto, Keisuke Hieda, Keisuke Hayashi, Tetsutaro Hinata, Nobuyuki Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title | Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title_full | Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title_fullStr | Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title_full_unstemmed | Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title_short | Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
title_sort | complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773190/ https://www.ncbi.nlm.nih.gov/pubmed/36568232 http://dx.doi.org/10.3389/fonc.2022.1039383 |
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