PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

<div><p>PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer.</p></div

Kaplan-Meier survival curves of gastric carcinoma patients with and without tumor expression of PRR11.

<p>(A) Survival was significantly longer in patients with tumor lacking expression of PRR11 (OS, 76.6 month) versus those with positive PRR11 expression status (OS, 46.6 month; P < 0.001). (B) A subgroup analysis of stage I & II patients revealed that patients with a positive PRR11 expression status was associated with a shorter survival duration than patients without PRR11 expression (58.5mon vs. 97.9mon; <i>P</i><0.001). (C) A subgroup analysis of stage III & IV patients demonstrated that positive PRR11 overexpression was associated with a shorter overall survival than patients without PRR11 expression (34.3mon vs. 51.3mon; <i>P</i> = 0.036).</p

Univariate and Multivariate Analysis of Variables Associated with OS in Patients with gastric cancer.

<p>Univariate and Multivariate Analysis of Variables Associated with OS in Patients with gastric cancer.</p

Knock down of PRR11 inhibited cell proliferation and GC cell colony forming ability in the SGC-7901 gastric carcinoma cell line.

<p>(A) Western blot analysis of PRR11 expression at 48 hours after transfection of PRR11-shRNA in SGC7901 cells; (B, C) Silencing of PRR11 inhibits cell proliferation (B) and colony forming ability in vitro (C). (D) Silencing of PRR11 inhibited tumor grow in vivo. *P<0.05, **P<0.01, **P<0.01 considered statistically significant compared with control.</p

Analysis of PRR11 expression in human gastric cancers and adjacent normal mucosa specimens.

<p>(A, A1) Normal gastric mucosa showed weak staining of PRR11; (B, B1) Positive staining of PRR11 in gastric cancer; (C, C1) Negative staining of PRR11 in gastric cancer. A1, B1, C1 are enlargement of tissues from A, B, C, respectively. Original magnification of A, B, C: 40×; Original magnification of A1, B1, C1: 200×. (D) Western blotting revealed increased expression of PRR11 in tumor samples (T) compared with that in noncancerous tissues (N); (E) mRNA levels of PRR11 in gastric cancer tissues (T) and normal tissues (N).</p

Correlation between overexpression of PRR11 and clinicopathological of gastric cancer.

<p>Correlation between overexpression of PRR11 and clinicopathological of gastric cancer.</p

Correlation between expression of PRR11, LXN and CTHRC1 in gastric carcinoma samples.

<p>(A) Western blot analysis showing that CTHRC1 is down-regulated and LXN is up-regulated in PRR11-KO SGC07901 cells. (B) Expression of PRR11, CTHRC1 and LXN in patients-derived gastric carcinoma tissue samples. (C) Correlation analysis of PRR11, CTHRC1 and LXN expression. These results were interpreted as showing that CTHRC1 expression is positively associated with PRR11 expression (r = 0.299, p<0.001) and that LXN expression is negatively associated with PRR11 expression (r = -0.188, p = 0.005) in GC tissues.</p