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Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63

Cancers acquire resistance to systemic treatment with platinum‐based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single‐cell level. Here, mapping the...

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Autores principales: Tanaka, Nobuyuki, Katayama, Shintaro, Reddy, Aparna, Nishimura, Kaneyasu, Niwa, Naoya, Hongo, Hiroshi, Ogihara, Koichiro, Kosaka, Takeo, Mizuno, Ryuichi, Kikuchi, Eiji, Mikami, Shuji, Miyakawa, Ayako, Arenas, Ernest, Kere, Juha, Oya, Mototsugu, Uhlén, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308066/
https://www.ncbi.nlm.nih.gov/pubmed/30367559
http://dx.doi.org/10.1002/cam4.1828
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author Tanaka, Nobuyuki
Katayama, Shintaro
Reddy, Aparna
Nishimura, Kaneyasu
Niwa, Naoya
Hongo, Hiroshi
Ogihara, Koichiro
Kosaka, Takeo
Mizuno, Ryuichi
Kikuchi, Eiji
Mikami, Shuji
Miyakawa, Ayako
Arenas, Ernest
Kere, Juha
Oya, Mototsugu
Uhlén, Per
author_facet Tanaka, Nobuyuki
Katayama, Shintaro
Reddy, Aparna
Nishimura, Kaneyasu
Niwa, Naoya
Hongo, Hiroshi
Ogihara, Koichiro
Kosaka, Takeo
Mizuno, Ryuichi
Kikuchi, Eiji
Mikami, Shuji
Miyakawa, Ayako
Arenas, Ernest
Kere, Juha
Oya, Mototsugu
Uhlén, Per
author_sort Tanaka, Nobuyuki
collection PubMed
description Cancers acquire resistance to systemic treatment with platinum‐based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single‐cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA‐seq, we uncovered a novel gene, COX7B, associated with platinum‐resistance, and surrogate marker, CD63. Knockdown of COX7B in cancer cells decreased the sensitivity of CDDP whereas overexpression recovered the sensitivity of CDDP. Low COX7B levels correlated with higher mortality rates in patients with various types of cancer and were significantly associated with poor response to chemotherapy in urinary bladder cancer. Tumor samples from patients, who underwent CDDP therapy, showed decreased COX7B protein levels after the treatment. Analyzing scRNA‐seq data from platinum‐naïve cancer cells demonstrated a low‐COX7B subclone that could be sorted out from bulk cancer cells by assaying CD63. This low‐COX7B subclone behaved as cells with acquired platinum‐resistance when challenged to CDDP. Our results offer a new transcriptome landscape of platinum‐resistance that provides valuable insights into chemosensitivity and drug resistance in cancers, and we identify a novel platinum resistance gene, COX7B, and a surrogate marker, CD63.
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spelling pubmed-63080662019-01-03 Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63 Tanaka, Nobuyuki Katayama, Shintaro Reddy, Aparna Nishimura, Kaneyasu Niwa, Naoya Hongo, Hiroshi Ogihara, Koichiro Kosaka, Takeo Mizuno, Ryuichi Kikuchi, Eiji Mikami, Shuji Miyakawa, Ayako Arenas, Ernest Kere, Juha Oya, Mototsugu Uhlén, Per Cancer Med Cancer Biology Cancers acquire resistance to systemic treatment with platinum‐based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single‐cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA‐seq, we uncovered a novel gene, COX7B, associated with platinum‐resistance, and surrogate marker, CD63. Knockdown of COX7B in cancer cells decreased the sensitivity of CDDP whereas overexpression recovered the sensitivity of CDDP. Low COX7B levels correlated with higher mortality rates in patients with various types of cancer and were significantly associated with poor response to chemotherapy in urinary bladder cancer. Tumor samples from patients, who underwent CDDP therapy, showed decreased COX7B protein levels after the treatment. Analyzing scRNA‐seq data from platinum‐naïve cancer cells demonstrated a low‐COX7B subclone that could be sorted out from bulk cancer cells by assaying CD63. This low‐COX7B subclone behaved as cells with acquired platinum‐resistance when challenged to CDDP. Our results offer a new transcriptome landscape of platinum‐resistance that provides valuable insights into chemosensitivity and drug resistance in cancers, and we identify a novel platinum resistance gene, COX7B, and a surrogate marker, CD63. John Wiley and Sons Inc. 2018-10-26 /pmc/articles/PMC6308066/ /pubmed/30367559 http://dx.doi.org/10.1002/cam4.1828 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Tanaka, Nobuyuki
Katayama, Shintaro
Reddy, Aparna
Nishimura, Kaneyasu
Niwa, Naoya
Hongo, Hiroshi
Ogihara, Koichiro
Kosaka, Takeo
Mizuno, Ryuichi
Kikuchi, Eiji
Mikami, Shuji
Miyakawa, Ayako
Arenas, Ernest
Kere, Juha
Oya, Mototsugu
Uhlén, Per
Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title_full Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title_fullStr Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title_full_unstemmed Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title_short Single‐cell RNA‐seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63
title_sort single‐cell rna‐seq analysis reveals the platinum resistance gene cox7b and the surrogate marker cd63
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308066/
https://www.ncbi.nlm.nih.gov/pubmed/30367559
http://dx.doi.org/10.1002/cam4.1828
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