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Int J Clin Exp Pathol 2013;6(2):148-154
Original Article
Amplified RPS6KB1 and CDC2 genes are potential
biomarkers for aggressive HIV+/EBV+ diffuse large
B-cell lymphomas
Xianfeng F Zhao, Merry Y Zhao, Ling Chai, Debra Kukuruga, Ming Tan, Sanford A Stass
Department of Pathology, Division of Biostatistics, Marlene and Stewart Greenebaum Cancer Center, University
of Maryland School of Medicine, Baltimore, MD, USA
Received November 2, 2012; Accepted November 27, 2012; Epub January 15, 2013; Published February 1, 2013
Abstract: RPS6KB1 encodes p70S6K/p85S6K, which plays a role in the PI3K/Akt/mTOR signal transduction pathway.
CDC2 gene encodes cdc2, which is critical for G2/M cell cycle progression. We had previously shown that
amplified RPS6KB1 and CDC2 are commonly detected in the EBV+ diffuse large B-cell lymphoma (DLBCL) in HIV
patients. In current study, we further evaluated the amplified RPS6KB1 and CDC2 genes in 12 HIV-related aggressive
B-cell lymphomas and 10 non-HIV-related DLBCL using real time quantitative PCR. The cases were divided into
4 groups: 1) HIV-/EBV-; 2) HIV-/EBV+; 3) HIV+/EBV-; and 4) HIV+/EBV+. Receiver operating characteristic (ROC)
curve and the area under the curve (AUC) was used to assess the ability of each gene to distinguish non-HIV+/EBV+
cases from HIV+/EBV+ cases. The AUC was estimated to be 0.76 for RPS6KB1 and 0.74 for CDC2 by using the
Mann–Whitney statistic. Amplified RPS6KB1 and CDC2 genes were more frequently detected in common variants
of DLBCL associated with HIV infection. Taken together, amplified RPS6KB1 and CDC2 are potential biomarkers for
the aggressive DLBCL, particularly in HIV+/EBV+ patients. This study also suggests that the HIV+/EBV+ aggressive
DLBCL could be potentially treated by targeting RPS6KB1 and CDC2 genes. (IJCP1211002).
Keywords: RPS6KB1, CDC2, HIV, EBV, lymphoma, biomarker
Address all correspondence to:
Dr. X Frank Zhao
Department of Pathology
University of California San Diego
VAMC-San Diego, West 3051
3350 La Jolla Village Drive
San Diego, CA 92161, USA.
Tel: 858-5528585, Ext. 2465; Fax: 858-6423918
E-mail: Frank.Zhao2@va.gov
Original Article
Amplified RPS6KB1 and CDC2 genes are potential
biomarkers for aggressive HIV+/EBV+ diffuse large
B-cell lymphomas
Xianfeng F Zhao, Merry Y Zhao, Ling Chai, Debra Kukuruga, Ming Tan, Sanford A Stass
Department of Pathology, Division of Biostatistics, Marlene and Stewart Greenebaum Cancer Center, University
of Maryland School of Medicine, Baltimore, MD, USA
Received November 2, 2012; Accepted November 27, 2012; Epub January 15, 2013; Published February 1, 2013
Abstract: RPS6KB1 encodes p70S6K/p85S6K, which plays a role in the PI3K/Akt/mTOR signal transduction pathway.
CDC2 gene encodes cdc2, which is critical for G2/M cell cycle progression. We had previously shown that
amplified RPS6KB1 and CDC2 are commonly detected in the EBV+ diffuse large B-cell lymphoma (DLBCL) in HIV
patients. In current study, we further evaluated the amplified RPS6KB1 and CDC2 genes in 12 HIV-related aggressive
B-cell lymphomas and 10 non-HIV-related DLBCL using real time quantitative PCR. The cases were divided into
4 groups: 1) HIV-/EBV-; 2) HIV-/EBV+; 3) HIV+/EBV-; and 4) HIV+/EBV+. Receiver operating characteristic (ROC)
curve and the area under the curve (AUC) was used to assess the ability of each gene to distinguish non-HIV+/EBV+
cases from HIV+/EBV+ cases. The AUC was estimated to be 0.76 for RPS6KB1 and 0.74 for CDC2 by using the
Mann–Whitney statistic. Amplified RPS6KB1 and CDC2 genes were more frequently detected in common variants
of DLBCL associated with HIV infection. Taken together, amplified RPS6KB1 and CDC2 are potential biomarkers for
the aggressive DLBCL, particularly in HIV+/EBV+ patients. This study also suggests that the HIV+/EBV+ aggressive
DLBCL could be potentially treated by targeting RPS6KB1 and CDC2 genes. (IJCP1211002).
Keywords: RPS6KB1, CDC2, HIV, EBV, lymphoma, biomarker
Address all correspondence to:
Dr. X Frank Zhao
Department of Pathology
University of California San Diego
VAMC-San Diego, West 3051
3350 La Jolla Village Drive
San Diego, CA 92161, USA.
Tel: 858-5528585, Ext. 2465; Fax: 858-6423918
E-mail: Frank.Zhao2@va.gov
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