KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer

Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is reported to play an essential role in cancer. This study aimed to analyze KIFC1 expression and examine KIFC1 involvement in cisplatin resistance in bladder cancer (BC). I...

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Autores principales:	Yohei Sekino, Quoc Thang Pham, Kohei Kobatake, Hiroyuki Kitano, Kenichiro Ikeda, Keisuke Goto, Tetsutaro Hayashi, Hikaru Nakahara, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Jun Teishima, Nobuyuki Hinata
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bladder cancer <i>KIFC1</i> basal type p53 cisplatin PD-L1 Medicine R
Acceso en línea:	https://doaj.org/article/73f7bc82541044febfe156f830d7a528
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spelling	oai:doaj.org-article:73f7bc82541044febfe156f830d7a5282021-11-11T17:30:18ZKIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer10.3390/jcm102148372077-0383https://doaj.org/article/73f7bc82541044febfe156f830d7a5282021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4837https://doaj.org/toc/2077-0383Kinesin family member C1 (<i>KIFC1</i>), a minus end-directed motor protein, is reported to play an essential role in cancer. This study aimed to analyze <i>KIFC1</i> expression and examine <i>KIFC1</i> involvement in cisplatin resistance in bladder cancer (BC). Immunohistochemistry showed that 37 of 78 (47.4%) BC cases were positive for <i>KIFC1</i>. <i>KIFC1</i>-positive cases were associated with high T stage and lymph node metastasis. Kaplan-Meier analysis showed that <i>KIFC1</i>-positive cases were associated with poor prognosis, consistent with the results from public databases. Molecular classification in several public databases indicated that <i>KIFC1</i> expression was increased in basal type BC. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with basal markers 34βE12, CK5 and CD44. <i>KIFC1</i> expression was increased in altered <i>TP53</i> compared to that in wild-type <i>TP53</i>. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with p53-positive cases. P53 knockout by CRISPR-Cas9 induced <i>KIFC1</i> expression in BC cell lines. Knockdown of <i>KIFC1</i> by siRNA increased the sensitivity to cisplatin in BC cells. Kaplan-Meier analysis indicated that prognosis was poor among <i>KIFC1</i>-positive BC patients treated with cisplatin-based chemotherapy. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with PD-L1-positive cases. High <i>KIFC1</i> expression was associated with a favorable prognosis in patients treated with atezolizumab from the IMvigor 210 study. These results suggest that <i>KIFC1</i> might be a promising biomarker and therapeutic target in BC.Yohei SekinoQuoc Thang PhamKohei KobatakeHiroyuki KitanoKenichiro IkedaKeisuke GotoTetsutaro HayashiHikaru NakaharaKazuhiro SentaniNaohide OueWataru YasuiJun TeishimaNobuyuki HinataMDPI AGarticlebladder cancer<i>KIFC1</i>basal typep53cisplatinPD-L1MedicineRENJournal of Clinical Medicine, Vol 10, Iss 4837, p 4837 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer <i>KIFC1</i> basal type p53 cisplatin PD-L1 Medicine R
spellingShingle	bladder cancer <i>KIFC1</i> basal type p53 cisplatin PD-L1 Medicine R Yohei Sekino Quoc Thang Pham Kohei Kobatake Hiroyuki Kitano Kenichiro Ikeda Keisuke Goto Tetsutaro Hayashi Hikaru Nakahara Kazuhiro Sentani Naohide Oue Wataru Yasui Jun Teishima Nobuyuki Hinata KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
description	Kinesin family member C1 (<i>KIFC1</i>), a minus end-directed motor protein, is reported to play an essential role in cancer. This study aimed to analyze <i>KIFC1</i> expression and examine <i>KIFC1</i> involvement in cisplatin resistance in bladder cancer (BC). Immunohistochemistry showed that 37 of 78 (47.4%) BC cases were positive for <i>KIFC1</i>. <i>KIFC1</i>-positive cases were associated with high T stage and lymph node metastasis. Kaplan-Meier analysis showed that <i>KIFC1</i>-positive cases were associated with poor prognosis, consistent with the results from public databases. Molecular classification in several public databases indicated that <i>KIFC1</i> expression was increased in basal type BC. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with basal markers 34βE12, CK5 and CD44. <i>KIFC1</i> expression was increased in altered <i>TP53</i> compared to that in wild-type <i>TP53</i>. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with p53-positive cases. P53 knockout by CRISPR-Cas9 induced <i>KIFC1</i> expression in BC cell lines. Knockdown of <i>KIFC1</i> by siRNA increased the sensitivity to cisplatin in BC cells. Kaplan-Meier analysis indicated that prognosis was poor among <i>KIFC1</i>-positive BC patients treated with cisplatin-based chemotherapy. Immunohistochemistry showed that <i>KIFC1</i>-positive cases were associated with PD-L1-positive cases. High <i>KIFC1</i> expression was associated with a favorable prognosis in patients treated with atezolizumab from the IMvigor 210 study. These results suggest that <i>KIFC1</i> might be a promising biomarker and therapeutic target in BC.
format	article
author	Yohei Sekino Quoc Thang Pham Kohei Kobatake Hiroyuki Kitano Kenichiro Ikeda Keisuke Goto Tetsutaro Hayashi Hikaru Nakahara Kazuhiro Sentani Naohide Oue Wataru Yasui Jun Teishima Nobuyuki Hinata
author_facet	Yohei Sekino Quoc Thang Pham Kohei Kobatake Hiroyuki Kitano Kenichiro Ikeda Keisuke Goto Tetsutaro Hayashi Hikaru Nakahara Kazuhiro Sentani Naohide Oue Wataru Yasui Jun Teishima Nobuyuki Hinata
author_sort	Yohei Sekino
title	KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
title_short	KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
title_full	KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
title_fullStr	KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
title_full_unstemmed	KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer
title_sort	kifc1 is associated with basal type, cisplatin resistance, pd-l1 expression and poor prognosis in bladder cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/73f7bc82541044febfe156f830d7a528
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KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer

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