Pancreatic adenocarcinoma up-regulated factor expression is associated with disease-specific survival in cervical cancer patients

Abstract

Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel soluble protein involved in tumor development and metastases. This study was to investigate the PAUF expression and its prognostic value in cervical cancer patients. The expression of PAUF was immunohistochemically determined in 345 formalin-fixed, paraffin-embedded cervical cancer tissues and 107 normal cervical epitheliums. Subsequently, its associations with clinicopathological characteristics and patient survival were assessed. PAUF protein was expressed both in cytoplasm and nucleus, and cytoplasmic expression was more frequent in cancers than normal tissues (32% versus 17%, P = .002), and the difference was prominent in glandular cells. Notably, the expression was more frequent in adenocarcinoma than in squamous cell carcinoma (57% versus 25%, respectively; P < .001), and the differential expression was also seen at the messenger RNA level (P = .014). Cox regression analysis showed that the cytoplasmic expression of PAUF protein was independently associated with poor disease-free (hazard ratio = 2.3; 95% confidence interval, 1.2-4.3; P = .008) and overall survival (hazard ratio = 2.9; 95% confidence interval, 1.2-7.5; P = .020). Detection of PAUF expression may aid current evaluation of prognosis in cervical adenocarcinoma.

Keywords: Adenocarcinoma; PAUF; Prognosis; Survival; Uterine cervical neoplasms.

Fig. 1

DFS according to mRNA expression of PAUF. Data are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44001.

Fig. 2

Western blotting in HeLa cells. PAUF protein expression was detected in both cytosolic and nuclear fractions. Calnexin and Lamin B1 were used as an index for cytosolic or nuclear fraction, respectively.

Fig. 3

Representative examples of negative (A, C, E, and G) and positive (B, D, F, and H) PAUF expressions. Normal squamous cell (A and B); normal glandular cell (C and D); squamous cell carcinoma (E and F); and adenocarcinoma (G and H). I, More frequent cytoplasmic PAUF expression was found in adenocarcinoma rather than in normal glandular cells, which relationship was not seen with SCC. J, Nuclear PAUF expression is not different between cancer and normal cells (×200). The scale bar represents 100 μm.

Fig. 4

mRNA expression of PAUF according to cell type. Data were obtained from GSE44001 (n = 300) (A), TCGA cervical cancer (n = 257) (B), and TCGA normalized pan-cancer (n = 4537) (C).

Fig. 5

Kaplan-Meier survival curves according to PAUF expression. Cytoplasmic expression (B and D) was associated with poor survival, whereas nuclear expression did not (A and C). P values were obtained from log-rank tests.

Fig. 6

Kaplan-Meier plot for DFS (A) and OS (B) survival categorized based on PAUF expression and cell type.