Limits...
Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC).

Methods:: The study population consisted of 856 patients with stage I–III CRC from two hospitals. RRBP1 expression was examined by immunohistochemisty (IHC) in colorectal tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated in a training-validation design with univariate and multivariate Cox analysis. Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was evaluated in CRC cells.

Results:: RRBP1 was aberrantly overexpressed in CRC. Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease-specific survival in the training (hazard ratio (HR), 2.423; 95% confidence interval (CI), 1.531–3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166–6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter disease-free survival (HR, 4.821; 95% CI, 3.220–7.218) in the validation cohort. RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited the growth of CRC xenografts in vivo.

Conclusions:: High RRBP1 expression facilitates CRC progression and predicts an unfavourable post-operative prognosis.

No MeSH data available.


Related in: MedlinePlus

High IHC-score of RRBP1 predicts poor survivals of patients with CRC. Patients with stage I–III, stage I–II or stage III tumour were dichotomised into the subgroups with high- or low-RRBP1 protein expression according to RRBP1 IHC-score (cut-off value=175) in the Shuguang and Changhai cohorts, respectively. Disease-specific survival and DFS are presented. Log-rank P values and hazard ratios (HRs) from univariate Cox regression analysis are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4559827&req=5

fig2: High IHC-score of RRBP1 predicts poor survivals of patients with CRC. Patients with stage I–III, stage I–II or stage III tumour were dichotomised into the subgroups with high- or low-RRBP1 protein expression according to RRBP1 IHC-score (cut-off value=175) in the Shuguang and Changhai cohorts, respectively. Disease-specific survival and DFS are presented. Log-rank P values and hazard ratios (HRs) from univariate Cox regression analysis are shown.

Mentions: Immunohistochemisty-scores of CRC specimens from Shuguang Hospital were further analysed to investigate the prognostic value of RRBP1. When tested as a continuous variable, the IHC-score of RRBP1 was significantly associated with DSS (P<0.001). In exploratory analysis with different cut-off values to define patient subgroups with high RRBP1 or low RRBP1, we found that the cut-off value of 175 of IHC-score identified by X-tile software could most effectively discriminate the differences of DSS. Using the cut-off value, we also found that RRBP1 expression may be uncorrelated to many clinicopathologic characteristics of CRC patients, such as age, sex, tumour location, differentiation grade and TNM stage (Table 1). Kaplan–Meier analysis showed that patients with high RRBP1 (IHC-score >175) were significantly associated with a shorter DSS than those with low RRBP1 (IHC score ⩽175) (Figure 2). Including high expression of RRBP1, other factors such as TNM stage and differentiation grade, were also significantly associated with DSS of CRC patients in univariate Cox analysis (Table 2). Multivariate Cox regression analysis showed high RRBP1 in CRC remained a statistically significant predictor for DSS (hazard ratio, 2.423; 95% confidence interval, 1.531–3.835) after adjusting for variables as stage, grade, age, sex, tumour size, depth of tumour invasion and tumour location (Table 2). Notably, patients with high RRBP1 were significantly associated with a poor DSS in both stage (I+II) CRC and stage III CRC (Figure 2).


Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis
High IHC-score of RRBP1 predicts poor survivals of patients with CRC. Patients with stage I–III, stage I–II or stage III tumour were dichotomised into the subgroups with high- or low-RRBP1 protein expression according to RRBP1 IHC-score (cut-off value=175) in the Shuguang and Changhai cohorts, respectively. Disease-specific survival and DFS are presented. Log-rank P values and hazard ratios (HRs) from univariate Cox regression analysis are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559827&req=5

fig2: High IHC-score of RRBP1 predicts poor survivals of patients with CRC. Patients with stage I–III, stage I–II or stage III tumour were dichotomised into the subgroups with high- or low-RRBP1 protein expression according to RRBP1 IHC-score (cut-off value=175) in the Shuguang and Changhai cohorts, respectively. Disease-specific survival and DFS are presented. Log-rank P values and hazard ratios (HRs) from univariate Cox regression analysis are shown.
Mentions: Immunohistochemisty-scores of CRC specimens from Shuguang Hospital were further analysed to investigate the prognostic value of RRBP1. When tested as a continuous variable, the IHC-score of RRBP1 was significantly associated with DSS (P<0.001). In exploratory analysis with different cut-off values to define patient subgroups with high RRBP1 or low RRBP1, we found that the cut-off value of 175 of IHC-score identified by X-tile software could most effectively discriminate the differences of DSS. Using the cut-off value, we also found that RRBP1 expression may be uncorrelated to many clinicopathologic characteristics of CRC patients, such as age, sex, tumour location, differentiation grade and TNM stage (Table 1). Kaplan–Meier analysis showed that patients with high RRBP1 (IHC-score >175) were significantly associated with a shorter DSS than those with low RRBP1 (IHC score ⩽175) (Figure 2). Including high expression of RRBP1, other factors such as TNM stage and differentiation grade, were also significantly associated with DSS of CRC patients in univariate Cox analysis (Table 2). Multivariate Cox regression analysis showed high RRBP1 in CRC remained a statistically significant predictor for DSS (hazard ratio, 2.423; 95% confidence interval, 1.531–3.835) after adjusting for variables as stage, grade, age, sex, tumour size, depth of tumour invasion and tumour location (Table 2). Notably, patients with high RRBP1 were significantly associated with a poor DSS in both stage (I+II) CRC and stage III CRC (Figure 2).

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC).

Methods:: The study population consisted of 856 patients with stage I&ndash;III CRC from two hospitals. RRBP1 expression was examined by immunohistochemisty (IHC) in colorectal tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated in a training-validation design with univariate and multivariate Cox analysis. Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was evaluated in CRC cells.

Results:: RRBP1 was aberrantly overexpressed in CRC. Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease-specific survival in the training (hazard ratio (HR), 2.423; 95% confidence interval (CI), 1.531&ndash;3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166&ndash;6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter disease-free survival (HR, 4.821; 95% CI, 3.220&ndash;7.218) in the validation cohort. RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited the growth of CRC xenografts in vivo.

Conclusions:: High RRBP1 expression facilitates CRC progression and predicts an unfavourable post-operative prognosis.

No MeSH data available.


Related in: MedlinePlus