J Pathol Transl Med.  2022 Jan;56(1):40-47. 10.4132/jptm.2021.10.07.

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer

• Oh H
• Kim SG
• Bae SU
• Byun SJ
• Kim S
• Lee JH
• Hwang I
• Kwon SY
• Lee HW

• KMID: 2524228
• DOI: http://doi.org/10.4132/jptm.2021.10.07

Abstract

Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Keyword

Polo-like kinase 4; Rectal neoplasms; Chemoradiotherapy; Biomarker

Figure

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  Fig. 1 Immunohistochemistry analyses of PLK4 expression in rectal cancer tissues. The expression of PLK is evaluated by H-score; intensity multiplied by percentage of positive cells. (A) Score 0 (negative staining) of PLK4 expression of pre-CRT specimen. (B) Score 1 (weak staining) of PLK4 expression of pre-CRT specimen. (C) Score 2 (medium staining) of PLK4 expression of pre-CRT specimen. (D) Score 3 (strong staining) of PLK4 expression of pre-CRT specimen. (E) Score 0 (negative staining) of PLK4 expression of post-CRT specimen. (F) Score 1 (weak staining) of PLK4 expression of post-CRT specimen. (G) Score 2 (medium staining) of PLK4 expression of post-CRT specimen. (H) Score 3 (strong staining) of PLK4 expression of post-CRT specimen. PLK4, Polo-like kinase 4; CRT, chemoradiotherapy.

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  Fig. 2 (A) Kaplan-Meier curves of disease-free survival in high and low expression of nuclear expression of PLK4 of pre-CRT specimen. (B) Kaplan-Meier curves of disease-free survival in high and low expression of cytoplasmic expression of PLK4 of pre-CRT specimen. (C) Kaplan-Meier curves of overall survival in high and low nuclear expression of PLK4 of pre-CRT specimen. (D) Kaplan-Meier curves of overall survival in high and low expression of cytoplasmic expression of PLK4 of pre-CRT specimen. PLK4, Polo-like kinase 4; CRT, chemoradiotherapy.

Reference

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