Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma

Our plain-English summary of Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma, by T. Kato, D. Lee, L. Wu, et al (International Journal of Oncology, 2016).

The study

• Authors: T. Kato, D. Lee, L. Wu, P. Patel, A.J. Young, H. Wada, H.P. Hu, H. Ujiie, M. Kaji, S. Kano, S. Matsuge, H. Domen, K. Kaga, Y. Matsui, H. Kanno, Y. Hatanaka, K.C. Hatanaka, Y. Matsuno, M. de Perrot, K. Yasufuku
• Journal: International Journal of Oncology
• Published: 2016;49(2):448-56
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.

In plain English

The authors studied two genes, KIF11 and KIF23, as possible drug targets in malignant pleural mesothelioma. No asbestos-exposure measurements are reported in this article. Gene-activity testing showed both genes highly active in most of 13 tumor samples from Toronto General Hospital and in four mesothelioma cell lines, but low in a normal mesothelial cell line. Reducing the genes' activity in two cell lines (H28 and H2052) significantly slowed cell growth by day 4. The authors then stained tumor tissue from 53 surgical patients in Sapporo, Japan, operated on between 1990 and 2012. High KIF11 was found in 23 of 53 cases (43.4%) and high KIF23 in 27 of 53 (50.9%). The cut-offs for 'high' were chosen as those giving the lowest P-value in the survival test. Among the 21 patients who had curative surgery, those with high KIF23 had shorter overall 5-year survival (P=0.0194). KIF11 showed a similar trend that was not statistically significant. The authors concluded these genes may become new treatment targets. They noted that the small sample size means the survival result needs confirming.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: gene-expression testing (quantitative RT-PCR) of tumor samples and cell lines, gene-silencing (siRNA) experiments in cell lines, and immunohistochemistry on a tissue microarray of archived surgical tumor samples with survival analysis
• Who was studied: 13 malignant pleural mesothelioma samples (6 epithelioid, 6 biphasic, 1 sarcomatoid) from Toronto General Hospital, Canada. 53 malignant pleural mesotheliomas from patients who had surgery at Hokkaido University Hospital and an affiliated hospital, Japan, February 1990 to April 2012 (49 male, 4 female; mean age 65.5). Four mesothelioma cell lines and one normal mesothelial cell line (MES-F).
• Exposure: No asbestos-exposure measurements are reported in this article. The study measured expression of the kinesin genes KIF11 and KIF23. High versus low expression was defined by immunohistochemical score cut-offs (0.7 for KIF11, 0.4 for KIF23), chosen as the threshold giving the lowest log-rank P-value.
• Main results:
  • KIF11 and KIF23 were overexpressed in a majority of the mesothelioma clinical samples tested by quantitative RT-PCR. Expression was high in 4 mesothelioma cell lines and low in the normal mesothelial cell line MES-F.
  • siRNA treatment significantly decreased KIF11 and KIF23 mRNA levels compared with control siRNA at 48 hours.
  • After siRNA treatment, proliferation of the H28 and H2052 cell lines was significantly suppressed compared with controls at day 4.
  • Of the 53 cases, high KIF11 expression was found in 23 (43.4%) and high KIF23 expression in 27 (50.9%).
  • High KIF23 was found in 22 of 34 epithelioid cases (64.7%) and 5 of 13 biphasic cases (38.5%). It was found in no sarcomatoid or desmoplastic cases.
  • In curative operative cases, no significant association was found between KIF11 or KIF23 expression and other clinicopathological variables.
  • Among patients who received curative resection (n=21), those with high KIF23 had shorter overall 5-year survival than those with low KIF23 (P=0.0194). KIF11 showed a similar trend that was not statistically significant.
• The authors' conclusion: The authors concluded that KIF11 and KIF23 are highly expressed in most mesothelioma cases and are crucial for the growth of mesothelioma cells. They concluded that high KIF23 is associated with poor survival, and that these genes may have a future role as new therapeutic targets.
• Limitations the authors state:
  • The survival result needs to be validated in another tissue microarray set because of the small sample size.
  • Before tissue microarray results are linked with individual survival, whole-section staining should check whether KIF23 expression is uniform within each tumor.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, STEM, Mesothelium, Overall Survival.

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