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Cancer Med. 2018 Dec;7(12):6193-6204. doi: 10.1002/cam4.1828. Epub 2018 Oct 26.

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

Author information

1
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
2
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
3
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
4
Department of Diagnostic Pathology, Keio University Hospital, Tokyo, Japan.
5
Department of Urology, Karolinska University Hospital, Solna, Sweden.
6
Department of Medical and Molecular Genetics, King's College London, London, UK.
7
Keio University Graduate School of Medicine, Tokyo, Japan.

Abstract

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.

KEYWORDS:

CD63; COX7B; platinum resistance; single-cell RNA-seq; tumor heterogeneity

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