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 (email@example.com) or Dr. J Zhou (firstname.lastname@example.org)
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