Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer

Abstract

Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like receptors (TLRs) and has been reported to be involved in pancreatic tumor development. However, the significance of PAUF expression in epithelial ovarian cancer remains unclear. We aimed to investigate the possible clinical significance of PAUF in epithelial ovarian cancer. We examined the link between PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by immunohistochemistry on tissue microarray of 408 ovarian samples ranging from normal to metastatic. PAUF expression positively correlated with TLR4 expression. Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001). Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high expression are independent prognostic factor for progression-free survival, while TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for overall survival. Our results suggest that PAUF has a role in ovarian cancer progression and is a potential prognostic marker and novel chemotherapeutic target for ovarian cancer.

Pancreatic adenocarcinoma up-regulated factor as a target for the treatment of serous ovarian adenocarcinoma

“…Recent reports indicate that PAUF is overexpressed in ovarian cancer [15,16], which is consistent with our previous observation that the PAUF transcript is elevated in the disease [7]. PAUF expression is associated with tumor grade and chemoresistance of epithelial ovarian cancer [15,16]. Furthermore, high expression of PAUF correlates with poor prognosis for both overall and progression-free survivals in epithelial ovarian cancer.…”

“…For preparation of secreted PAUF, cells were cultured for three days after seeding 7 x 10 5 cells followed by concentration of culture supernatant using a Vivaspin column (Sartorius) per manufacturer's recommendation. Detection of PAUF by ELISA was as described previously [16].…”

“…PAUF acts on: i) pancreatic cancer cells to promote tumorigenic progression and metastasis [7][8][9][10][11], ii) endothelial cells to induce angiogenesis in a tumor mass [12], and iii) immune cells to evade immune surveillance in the tumor microenvironment [13,14]. Recent reports indicate that PAUF is overexpressed in ovarian cancer [15,16], which is consistent with our previous observation that the PAUF transcript is elevated in the disease [7]. PAUF expression is associated with tumor grade and chemoresistance of epithelial ovarian cancer [15,16].…”

Circulating tumor cell characterization of lung cancer brain metastasis in the cerebrospinal fluid through single-cell transcriptome analysis

“…Among the nine genes with biased expression in the earlier stage P8-1 (Supplementary Table 6), MSMB (microseminoprotein beta, Figure 6d) is one of the most abundant proteins in semen(123-125) and it has been used for diagnosis of prostate cancer (126). ZG16B /PAUF (pancreatic adenocarcinoma-upregulated factor, Figure 6D) is a secreted protein with crucial role in pancreatic ductal adenocarcinoma (PDAC) (127-130), as well as other cancer types including epithelial ovarian cancer (131), cervical carcinoma (132), colorectal cancer (133) and oral squamous cell carcinoma (134). KLK5 (Kallikrein-related peptidases 5, Figure 6D) is in the same gene family as the prostate-specific antigen KLK3 , exerts key modulatory effects on many cancers(135-139) and it is selectively inhibited by SPINK, a family of serine peptidase inhibitor kazal type, which bind to their target serine proteases and inhibit their proteolytic function(140-145).…”

Identification of ZG16B as a prognostic biomarker in breast cancer

“…ZG16B is also confirmed to exist in HeLa cells and upregulates in cervical cancer [ 37 , 38 ]. Moreover, ZG16B can also have effect and be a biomarker for early diagnosis and prognosis of prostate cancer [ 39 ], oral squamous cell carcinoma [ 40 ], and especially ovarian cancer [ 41 , 42 , 43 ]. Besides, ZG16B is correlated with the prognosis of atherosclerosis and acute coronary syndrome [ 44 ], and it is demonstrated to be abundant in the reflex tears as the key point in the ocular surface protection, maintaining the tear film stability [ 45 , 46 ].…”