This study investigated the expression of RRBP1 in central and peripheral astrocytoma tissue samples. The results found that RRBP1 expression was higher, though not statistically significantly, in peripheral astrocytoma tissues compared to central tissues. RRBP1 expression was significantly correlated with proliferation marker Ki-67 and invasion marker MMP9 expression. This suggests that high RRBP1 expression may regulate astrocytoma proliferation and invasion. Further research is needed to understand the underlying mechanisms.

1. 23
OBJECTIVE: To develop new therapeutic targets for
astrocytoma and explore potential mechanisms regulat-
ing astrocytoma relapse.
STUDY DESIGN: Expression of RRBP1, MMP9, and
Ki-67 was investigated at the center and periphery of
astrocytoma tissues.
RESULTS: RRBP1 expression was higher in peripheral
than in central astrocytoma tissues, although the differ-
ence was not statistically significant. RRBP1 expression
was significantly correlated with that of proliferative
marker Ki-67 and invasive marker MMP9.
CONCLUSION: These results indicate that high RRBP1
expression may regulate astrocytoma proliferation and
invasion. However, further investigation is needed to
elucidate the underlying potential mechanisms. (Anal
Quant Cytopathol Histpathol 2019;41:23–26)
Keywords: astrocytoma; brain cancer; brain neo-
plasms, malignant; cell proliferation; glioblasto-
ma; MMP9; matrix metalloproteinase 9; neoplasm
invasion; ribosome binding protein 1; ribosomal
proteins; RRBP1.
Astrocytoma is the most common malignant brain
tumor, and glioblastoma is the most malignant
form of astrocytoma. Astrocytomas have an inva-
sive growth pattern and rapid recurrence after
surgery or chemotherapy. Patients with glioblas-
tomas have a median survival of less than 2 years.
No significant improvement in patient survival has
been achieved in recent years. Investigations of
the mechanisms of astrocytoma pathogenesis and
targeted therapy are current directions in astrocy-
toma research.
Ribosome binding protein 1 (RRBP1) is an en-
doplasmic reticulum membrane protein and is
re­
sponsible for ribosome binding and transmem-
brane protein translocation.1 RRBP1 is localized
mainly in the endoplasmic reticulum but is also
detected in the nucleus and cytoplasm.2 RRBP1
Analytical and Quantitative Cytopathology and Histopathology®
0884-6812/19/4101-0023/$18.00/0 © Science Printers and Publishers, Inc.
Analytical and Quantitative Cytopathology and Histopathology®
RRBP1 Expression in Paired Central and
Peripheral Astrocytoma Tissue Microarray
Yan Li, M.D., Ph.D., Baoshi Han, M.D., Youqiang Cui, M.D.,
Guangcun Liu, M.D., Ph.D., and Xianzeng Hou, M.D., Ph.D.
From Medical Research Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan; Reproductive Hospital Affiliated to
Shandong University, Jinan; and the Department of Neurosurgery, Qianfoshan Hospital Affiliated to Shandong University, Jinan,
P.R. China.
Dr. Li is Postdoc in cardiac arrythmia, Medical Research Center, Qianfoshan Hospital Affiliated to Shandong University.
Dr. Han is Master Student, Reproductive Hospital Affiliated to Shandong University.
Drs. Cui, Liu, and Hou are Neurosurgeons, Department of Neurosurgery, Qianfoshan Hospital Affiliated to Shandong University.
Drs. Li, Han, and Cui contributed equally to this work.
This study was supported by grants 2015BSB14042, ZR2013HL032, 2009GG20002053, and ZR2015CL030 from the Natural Science Foun-
dation of Shandong Province, China.
Address correspondence to: Xianzeng Hou, M.D., Ph.D., Department of Neurosurgery, Qianfoshan Hospital Affiliated to Shandong
University, No. 16766 Jingshi Road, Jinan 250021, P.R. China (houxianzeng@sina.com), or Guangcun Liu, M.D., Ph.D., Depart-
ment of Neurosurgery, Qianfoshan Hospital Affiliated to Shandong University, No. 16766 Jingshi Road, Jinan 250021, P.R. China
(13791126712@139.com).
Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

2. plays important roles in procollagen biosynthesis,
ribosome binding, microtubule binding, and cell
differentiation.1,3-5 RRBP1 overexpression has been
detected in colorectal, breast, lung, and esophageal
cancers.6-9 RRBP1 expression in astrocytomas has
not been reported previously.
Astrocytomas rapidly recur owing to their inva-
sive growth pattern and incomplete surgical resec-
tion. Treatment targeting residual or peripheral as-
trocytoma tissue is important in current research.
The aim of this study was to investigate RRBP1
expression in paired central and peripheral astro­
cytoma tissues using tissue microarray.
Materials and Methods
Eighty-nine formalin-fixed, paraffin-embedded sur-
gical specimens from 56 patients were collected
from April 2015 to August 2017 in the Neurosur-
gery Department of Qianfoshan Hospital Affiliated
to Shandong University. Twelve of these speci-
mens were relatively normal brain tissues from
12 patients with cerebral hemorrhage or trauma
requiring tissue resection for internal decompres-
sion. The remaining specimens consisted of 11 as-
trocytoma tissue samples from 11 patients and
66 samples from 33 astrocytoma patients with
both central and peripheral astrocytoma tissues.
The diagnosis and grading of the astrocytomas
were confirmed by pathologists from the Pathol-
ogy Department at Qianfoshan Hospital Affiliat-
ed to Shandong University according to the 2007
World Health Organization classification of brain
tumors.10 Among the 11 patients with astrocyto-
ma tissues, there were 3 grade 2, 5 grade 3, and
3 grade 4 astrocytomas. Among the 33 patients
with both central and peripheral astrocytoma tis-
sues, there were 2 grade 1, 4 grade 2, 7 grade 3,
and 20 grade 4 astrocytomas. Written informed
consent was acquired from patients or their rel-
atives. This study was approved by the Medical
Ethics Committee of Qianfoshan Hospital Affiliated
to Shandong University.
The tissues were assembled for tissue microar-
ray by Servicebio Company (Wuhan, China). The
immunohistochemical study was performed using
the streptavidin-biotin complex method. The pri-
mary antibodies were RRBP1 (AB95983; Abcam),
MMP9 (13667P; Cell Signaling Technology), and
Ki-67 (AB92742; Abcam). Immunohistochemical
staining and image analysis were performed by
Servicebio Company. The slides were scanned
by Pannoramic MIDI (3DHISTECH Ltd.). Quant­
Center and Pannoramic Viewer software were used
to analyze the pixels in the images. Brown pixels
represent positive staining (Figures 1 and 2), and
the ratio of brown pixels in each sample was cal-
culated. Paired t test and Spearman’s correlation
analysis using SPSS 17.0 software was adopted for
data analysis. p Values <0.05 were considered sta-
tistically significant.
Results
RRBP1 expression was slightly higher in periph-
eral astrocytoma tissues (73.29±28.03) than in cen-
tral astrocytoma tissues (67.16±30.13), although
the difference was not statistically significant (p=
0.175). MMP9 expression was significantly higher
in peripheral than in central (p=0.000) astrocytoma
tissues (Table I). RRBP1 expression was signifi-
cantly correlated with Ki-67 (p=0.000) and MMP9
(p=0.004) expression in the data array including
55 patients (Table II). In the data array including
32 patients, RRBP1 expression was significantly
correlated with Ki-67 expression in central astro­
cytoma tissues (p=0.02, R=0.410) but not in periph-
eral astrocytoma tissues, which may be due to lim-
ited samples. In the data array including 32 patients,
RRBP1 expression had no significant correlation
with MMP9 expression in central astro­
cytoma tis-
sues or peripheral astrocytoma tissues (data not
shown); this may be due to limited samples.
No significant difference in RRBP1 expression
was observed between tumors of different grades
(may be due to limited samples) in grade 1 and
grade 2 astrocytomas. Lower RRBP1 expression
was observed in relative normal brain tissues as
compared with astrocytoma tissues, though not
statistically significant (data not shown).
24 Analytical and Quantitative Cytopathology and Histopathology®
Li et al
Figure 1 RRBP1 expression in a grade 4 astrocytoma
(glioblastoma) tissue. Brown pixels represent positive staining,
and blue staining indicates the nucleus.

3. Discussion
In this study, RRBP1 expression was investigated
using astrocytoma tissue microarray. RRBP1 was
highly expressed in astrocytoma tissue (Figure 1)
(Table I), and its expression was significantly cor-
related with Ki-67 and MMP9 expression.
RRBP1 is an important marker of tumor malig­
nancy and poor prognosis. RRBP1 is a ribosome-
binding protein on the rough endoplasmic reticu-
lum and is important in cellular protein transport.1
RRBP1 is overexpressed in lung cancer tissues as
compared with normal lung tissues.8 RRBP1 over-
expression can promote lung cancer growth in
vivo, whereas RRBP1 knockdown can reduce cell
viability and tumorigenicity.8 RRBP1 overexpres­
sion can also alleviate apoptosis induced by endo-
plasmic reticulum stress in lung cancer cells.8
RRBP1 is overexpressed in colorectal cancer tissue
as compared with adjacent normal tissue, and pa-
tients with high RRBP1 expression have a short-
er disease-free survival.11 RRBP1 is also overex-
pressed in breast cancer, and its overexpression is
correlated with a poor prognosis.7,12 In esophageal
cancer, RRBP1 is highly expressed and its expres-
sion is associated with tumor stage, lymph node
metastasis, and patient prognosis.9 A study showed
that Ki-67 expression was significantly increased in
the central area in grade II to grade IV gliomas.13
This study showed that RRBP1 was significantly
correlated with Ki-67 expression in central (corre­
lation coefficient 0.41, p=0.02) but not in periph-
eral astrocytoma tissues. RRBP1 was highly ex­
pressed in both peripheral and central astrocytoma
tissues (Table I). RRBP1 expression was higher in
peripheral than in central astrocytoma tissue, al-
though the difference was not statistically signifi-
cant (Table I). RRBP1 expression in astrocytomas
was significantly correlated with the expression of
MMP9 and Ki-67 (Table II), which are important
markers of invasive growth and cell proliferation,
respectively. The results indicate that RRBP1 may
play an important role in astrocytoma cell prolifer-
ation and invasion.
In conclusion, this study first investigated RRBP1
expression in astrocytoma tissues. RRBP1 expres-
sion is high in astrocytoma tissue and is signifi­
cantly correlated with MMP9 and Ki-67 expression.
The results indicate that RRBP1 may be a promis-
ing therapeutic target in astrocytomas.
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Volume 41, Number 1/February 2019 25
RRBP1 Expression in Astrocytoma Tissue Microarray
Figure 2 RRBP1 expression in a grade 1 astrocytoma tissue.
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Table I RRBP1, MMP9, and Ki-67 Expression in Paired Peripheral
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