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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

RRBP1 protein is elevated in colorectal cancer. (A) Representative examples of immunostaining of RRBP1 in CRC and adjacent normal tissues. RRBP1 is expressed in the cytoplasm of colorectal epithelial cells and stromal cells, and corresponding IHC-score was marked. Bar, 50 μm. (B) Expression pattern of RRBP1 protein in formalin-fixed paraffin-embedded specimens of CRC and adjacent normal tissues. The differences of RRBP1 protein expression between cancer vs normal, and stage (I+II) vs stage III are evaluated (stratified by lesion location).
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fig1: RRBP1 protein is elevated in colorectal cancer. (A) Representative examples of immunostaining of RRBP1 in CRC and adjacent normal tissues. RRBP1 is expressed in the cytoplasm of colorectal epithelial cells and stromal cells, and corresponding IHC-score was marked. Bar, 50 μm. (B) Expression pattern of RRBP1 protein in formalin-fixed paraffin-embedded specimens of CRC and adjacent normal tissues. The differences of RRBP1 protein expression between cancer vs normal, and stage (I+II) vs stage III are evaluated (stratified by lesion location).

Mentions: The expression pattern of RRBP1 was further investigated by IHC analysis on 174 paired cancer-adjacent specimens from Shuguang Hospital. RRBP1 staining was mainly distributed in the cytoplasm of colorectal epithelial cells and stromal cells (Figure 1A), and only the staining pattern in epithelial cells was further investigated. The median of IHC-score in CRC tissues was 181 (interquartile range, 131–214), and the median of IHC-score in normal tissues was 32 (interquartile range, 17–53). RRBP1 protein showed slight variation in normal tissues but great heterogeneity in cancer tissues. Results from the paired student t-test showed that the expression of RRBP1 protein was significantly higher in colon cancer and rectum cancer than that in corresponding adjacent specimens (all P<0.001) (Figure 1B). No differences were found between IHC-scores of stage CRC (I+II) and stage III CRC (Figure 1B) and between IHC-scores of colon cancer and rectum cancer specimens.


Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis
RRBP1 protein is elevated in colorectal cancer. (A) Representative examples of immunostaining of RRBP1 in CRC and adjacent normal tissues. RRBP1 is expressed in the cytoplasm of colorectal epithelial cells and stromal cells, and corresponding IHC-score was marked. Bar, 50 μm. (B) Expression pattern of RRBP1 protein in formalin-fixed paraffin-embedded specimens of CRC and adjacent normal tissues. The differences of RRBP1 protein expression between cancer vs normal, and stage (I+II) vs stage III are evaluated (stratified by lesion location).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: RRBP1 protein is elevated in colorectal cancer. (A) Representative examples of immunostaining of RRBP1 in CRC and adjacent normal tissues. RRBP1 is expressed in the cytoplasm of colorectal epithelial cells and stromal cells, and corresponding IHC-score was marked. Bar, 50 μm. (B) Expression pattern of RRBP1 protein in formalin-fixed paraffin-embedded specimens of CRC and adjacent normal tissues. The differences of RRBP1 protein expression between cancer vs normal, and stage (I+II) vs stage III are evaluated (stratified by lesion location).
Mentions: The expression pattern of RRBP1 was further investigated by IHC analysis on 174 paired cancer-adjacent specimens from Shuguang Hospital. RRBP1 staining was mainly distributed in the cytoplasm of colorectal epithelial cells and stromal cells (Figure 1A), and only the staining pattern in epithelial cells was further investigated. The median of IHC-score in CRC tissues was 181 (interquartile range, 131–214), and the median of IHC-score in normal tissues was 32 (interquartile range, 17–53). RRBP1 protein showed slight variation in normal tissues but great heterogeneity in cancer tissues. Results from the paired student t-test showed that the expression of RRBP1 protein was significantly higher in colon cancer and rectum cancer than that in corresponding adjacent specimens (all P<0.001) (Figure 1B). No differences were found between IHC-scores of stage CRC (I+II) and stage III CRC (Figure 1B) and between IHC-scores of colon cancer and rectum cancer specimens.

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