Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma

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 IL17 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.

Decreased interleukin‐17RA expression is associated with good prognosis in patients with colorectal cancer and inhibits tumor growth and vascularity in mice

“…18 Another study revealed that the low or loss of IL-17RA is significantly associated with advanced stage tumors. 17 In the present study, no abnormality was found in endogenous IL-17RA expression in CRC tissues and adjacent normal tissues. Further, IL-17RA expression was significantly higher in CRC tissues than in adjacent normal tissues based on RT-qPCR and IHC (Figure 1A,B).…”

“…Interestingly, the association between clinicopathological features and IL‐17RA expression in CRC remains unclear. According to previous studies, negative and lower expression levels of IL‐17RA are significantly associated with advanced stage and poor prognosis in patients with CRC 17,18 . However, ablation of IL‐17RA expression was found to reduce tumorigenesis in a sporadic CRC mouse model 10 .…”

Decreased interleukin-17RA expression is associated with good prognosis in patients with colorectal cancer and inhibits tumor growth and vascularity in mice

“…Another study revealed that the low or loss of IL-17RA is signi cantly associated with advanced stage tumors [17]. In the present study, no abnormality was found in endogenous IL-17RA expression in CRC tissues and adjacent normal tissues.…”

“…Interestingly, the association between clinicopathological features and IL-17RA expression in CRC remains unclear. According to previous studies, negative and lower expression levels of IL-17RA are signi cantly associated with advanced stage and poor prognosis in patients with CRC [17,18]. However, ablation of IL-17RA expression was found to reduce tumorigenesis in a sporadic CRC mouse model [10].…”

Interleukin-17 signaling influences CD8+T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells

“…Some of the processes like "Factors promoting carcinogenesis in vertebrates" are directly associated with cancer while others such as the "Axonal and synaptogenic signaling" have also been associated with tumor promotion given their role in apoptosis inhibition, cell migration and neural network formation that sustain tumor growth (81)(82)(83). So far, studies aimed at evaluating the role of IL-17 in cancer have focused on the expression of IL-17RA or IL-17RC separately (84,85) without a systematic analysis of the heterodimer relevance, with few exceptions (63). In addition, under the idea that IL-17 can only signal through the canonical IL-17RA/RC receptor complex, the evaluation of IL-17RD expression in tumors in the context of IL-17 signaling has not been incorporated yet (86).…”