Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma
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ORIGINAL ARTICLE
Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma Boon Yean Chai 1
&
Wai Kien Yip 1 & Noraini Dusa 2 & Norhafizah Mohtarrudin 3 & Heng Fong Seow 1,4
Received: 10 September 2019 / Revised: 14 April 2020 / Accepted: 12 May 2020 # Arányi Lajos Foundation 2020
Abstract Interleukin-17 (IL-17) is a pro-inflammatory cytokine found in various cancers. Current evidence indicates that IL-17 plays a vital role in tumour initiation and progression in colorectal carcinoma (CRC) via binding with its receptor, IL-17RA. However, the association between clinicopathological features and presence of IL-17 and IL-17RA protein in primary CRC tissues remains unclear. This study also investigates the difference between the presence of IL-17 and IL-17RA in the paired tumour tissues versus adjacent normal tissues. The presence of IL-17RA and IL-17 protein in primary CRC tissues was determined by immunohistochemistry. Associations between clinicopathological features and IL-17RA and IL-17 immunoreactivity, were analyzed by χ2 tests. We found that both IL-17RA (p = 0.001) and IL-17 (p = 0.025) in tumour cells of primary CRC tissues was significantly lower as compared to adjacent normal tissue. Positive immunoreactivity for IL-17RA and IL-17 were detected in 51.0% and 16.8% of tumour tissues, respectively. Furthermore, negative immunoreactivity of IL-17R was significantly associated with advanced stage according to TNM classifier (p = 0.027), high grade of tumour (p = 0.019), increased depth of tumour invasion (p = 0.023) and vascular invasion (p = 0.039). Positive IL-17 immunoreactivity was associated with advanced stage (p = 0.008) and lymph node metastasis (p = 0.008). Thus, this study suggests that the loss of IL-17RA expression occurs as tumour progresses and this may predict the aggressiveness of tumour whilst expression of IL-17 promotes tumour progression and lymph node metastasis. Thus, loss of IL-17RA could be a useful prognostic biomarker for tumour progression in CRC patients. Keywords IL-17 . IL-17RA . Colorectal carcinoma . Prognostic biomarker . Tumour progression
Introduction Colorectal carcinoma (CRC) is the third most common human cancer [1] with approximately one million new cases and
* Heng Fong Seow [email protected] 1
Immunology Laboratory, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia
2
Department of Pathology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
3
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia
4
Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia
more than 500,000 deaths every year [2]. Some patients respond well with conventional therapies while others do not respond [3]. Although CRC detection is possible through screening strategies with the advances in technology, CRC development a
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