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Online First

10.4103/aja202167

Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

Xian-Zi Zeng1, Zhan-Sen Huang1,2, Hong-Peng Fang1, Jie-Ying Wu1, Qun-Xiong Huang1, Chu-Bin Zhuang1, Jing Zhou3, Jin-Ming Di1

1 Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
2 Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
3 Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

Correspondence: Dr. JM Di (dijinm@mail.sysu.edu.cn) or Dr. J Zhou (zhouj36@mail.sysu.edu.cn)

05-Oct-2021

Abstract


Prostate cancer (PCa) is one of the most frequent cancers in men, and its biomolecular targets have been extensively studied. This study aimed to analyze the expression of toll-like receptor 9 (TLR9) and vascular endothelial growth factor C (VEGF-C) and the clinical value of the coexpression of TLR9 and VEGF-C in PCa. We retrospectively evaluated 55 patients with clinically localized, intermediate-risk, or high-risk PCa who underwent laparoscopic radical prostatectomy (LRP) and extended pelvic lymph node dissection (ePLND) without neoadjuvant hormonal therapy at a single institution from June 2013 to December 2016. In all 55 patients, the median number of lymph nodes (LNs) resected was 23 (range: 18–31), and a total of 1269 LNs were removed, of which 78 LNs were positive. Seventeen patients had positive LNs, with a positive rate of 30.9%. In addition, the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score (GS) (P = 0.049), increased LN metastasis (P = 0.004), and more perineural invasion (PNI) (P = 0.033). Moreover, VEGF-C expression was associated with GS (P = 0.040), pathological stage (pT stage) (P = 0.022), LN metastasis (P = 0.003), and PNI (P = 0.001). Furthermore, a significant positive correlation between TLR9 and VEGF-C was found (P < 0.001), and the TLR9/VEGF-C phenotype was associated with LN metastasis (P = 0.047). Collectively, we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression, thereby affecting the prognosis of PCa patients. Therefore, these markers may serve as valuable targets for the treatment of PCa.

Keywords: biochemical progression-free survival; coexpression; lymphatic metastasis; prostate cancer; toll-like receptor 9; vascular endothelial growth factor C

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