Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma

Hyunsung Kim, Yeseul Kim, Yumin Chung, Rehman Abdul, Jongmin Sim, Hyein Ahn, Su-Jin Shin, Seung Sam Paik, Han Joon Kim, Kiseok Jang, Dongho Choi

Research output: Contribution to journalArticle

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Abstract

Background: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. Methods: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10% of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. Results: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6%) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5%) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P < 0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. Conclusions: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.

Original languageEnglish
Article number1244
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - 2018 Dec 12

Fingerprint

DNA-Binding Proteins
Hepatocellular Carcinoma
Survival
Chi-Square Distribution
Gallbladder Neoplasms
Neoplasms
Immunohistochemistry
Cell Movement
Hepatocytes
Liver
Epithelial-Mesenchymal Transition
Genomic Instability
Kaplan-Meier Estimate
Hematologic Neoplasms
Glioblastoma
Bile Ducts
Ovarian Neoplasms
Disease-Free Survival
Endothelium
Blood Vessels

Keywords

  • Hepatocellular carcinoma
  • Immunohistochemistry
  • Prognosis
  • SSBP2
  • Single-stranded DNA binding protein 2

Cite this

Kim, Hyunsung ; Kim, Yeseul ; Chung, Yumin ; Abdul, Rehman ; Sim, Jongmin ; Ahn, Hyein ; Shin, Su-Jin ; Paik, Seung Sam ; Kim, Han Joon ; Jang, Kiseok ; Choi, Dongho. / Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
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title = "Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma",
abstract = "Background: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. Methods: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10{\%} of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. Results: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6{\%}) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5{\%}) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P < 0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. Conclusions: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.",
keywords = "Hepatocellular carcinoma, Immunohistochemistry, Prognosis, SSBP2, Single-stranded DNA binding protein 2",
author = "Hyunsung Kim and Yeseul Kim and Yumin Chung and Rehman Abdul and Jongmin Sim and Hyein Ahn and Su-Jin Shin and Paik, {Seung Sam} and Kim, {Han Joon} and Kiseok Jang and Dongho Choi",
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Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma. / Kim, Hyunsung; Kim, Yeseul; Chung, Yumin; Abdul, Rehman; Sim, Jongmin; Ahn, Hyein; Shin, Su-Jin; Paik, Seung Sam; Kim, Han Joon; Jang, Kiseok; Choi, Dongho.

In: BMC Cancer, Vol. 18, No. 1, 1244, 12.12.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma

AU - Kim, Hyunsung

AU - Kim, Yeseul

AU - Chung, Yumin

AU - Abdul, Rehman

AU - Sim, Jongmin

AU - Ahn, Hyein

AU - Shin, Su-Jin

AU - Paik, Seung Sam

AU - Kim, Han Joon

AU - Jang, Kiseok

AU - Choi, Dongho

PY - 2018/12/12

Y1 - 2018/12/12

N2 - Background: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. Methods: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10% of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. Results: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6%) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5%) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P < 0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. Conclusions: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.

AB - Background: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. Methods: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10% of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. Results: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6%) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5%) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P < 0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. Conclusions: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.

KW - Hepatocellular carcinoma

KW - Immunohistochemistry

KW - Prognosis

KW - SSBP2

KW - Single-stranded DNA binding protein 2

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U2 - 10.1186/s12885-018-5158-z

DO - 10.1186/s12885-018-5158-z

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