Abstract
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). Immunohistochemistry showed that 37 of 78 (47.4%) BC cases were positive for KIFC1. KIFC1-positive cases were associated with high T stage and lymph node metastasis. Kaplan-Meier analysis showed that KIFC1-positive cases were associated with poor prognosis, consistent with the results from public databases. Molecular classification in several public databases indicated that KIFC1 expression was increased in basal type BC. Immunohistochemistry showed that KIFC1-positive cases were associated with basal markers 34βE12, CK5 and CD44. KIFC1 expression was increased in altered TP53 compared to that in wild-type TP53. Immunohistochemistry showed that KIFC1-positive cases were associated with p53-positive cases. P53 knockout by CRISPR-Cas9 induced KIFC1 expression in BC cell lines. Knockdown of KIFC1 by siRNA increased the sensitivity to cisplatin in BC cells. Kaplan-Meier analysis indicated that prognosis was poor among KIFC1-positive BC patients treated with cisplatin-based chemotherapy. Immunohistochemistry showed that KIFC1-positive cases were associated with PD-L1-positive cases. High KIFC1 expression was associated with a favorable prognosis in patients treated with atezolizumab from the IMvigor 210 study. These results suggest that KIFC1 might be a promising biomarker and therapeutic target in BC.
Highlights
Bladder cancer (BC) is the 11th most commonly diagnosed cancer worldwide, with approximately 573,000 new cases and 213,000 deaths in 2020 [1]
Weak or no staining of Kinesin family member C1 (KIFC1) was observed in the non-neoplastic urothelium, whereas stronger and more extensive staining was observed in bladder cancer (BC) tissues (Figure 1A)
KaplanMeier analysis showed that KIFC1-positive cases were associated with poor prognosis after cisplatin-based chemotherapy (Figure 7C). These results suggest that KIFC1 may be a prognostic marker for cisplatin-based chemotherapy
Summary
Bladder cancer (BC) is the 11th most commonly diagnosed cancer worldwide, with approximately 573,000 new cases and 213,000 deaths in 2020 [1]. BC can be classified into two types: non-muscle-invasive BC and muscle-invasive BC (MIBC). In non-MIBC, T1 tumors are an aggressive subtype with 40% recurrence and 15% progression to MIBC at 5 years [2]. MIBC will eventually develop distant metastasis resulting in a 5 year survival rate of
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