Correlation of High Mobility Group Box-1 Protein (HMGB1) with Clinicopathological Parameters in Primary Retinoblastoma

Abstract

HMGB1 is considered to be DNA chaperone as it binds without any specificity. It is the structural protein which alters nuclear homeostasis and genomic stability of chromatin. Its role in retinoblastoma (Rb) remains unclear. The aim of the present study was to evaluate the expression of HMGB1 protein in primary enucleated retinoblastomas. Expression of HMGB1 in 69 prospective cases of primary retinoblastoma were assessed by immunohistochemistry and reverse transcriptase PCR (RT-PCR) technique and correlated with clinicopathological parameters. Immunohistochemical staining revealed expression of HMGB1 in 55.07 % (38/69) cases. Semi-quantitative RT-PCR was performed on 31 fresh tumor tissues. mRNA expression was observed in 77.41 % (24/31) cases. Expression of HMGB1 was statistically significant with poor tumor differentiation (p = 0.0440) & optic nerve invasion (p = 0.0128). HMGB1 expression was frequently seen in poorly differentiated tumors and those with histopathological high risk factors. Therefore, HMGB1 may contribute to tumor invasiveness and could serve as a poor prognostic marker in Rb.

<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/&beta;-catenin pathway</p>

“…41 It is also highly expressed in RB, and its overexpression is closely associated with poor tumor differentiation and optic nerve invasion. 42 HMGB1 increases oncogene activity in the genesis and development of RB, and it is involved in the regulation of RB cell proliferation, autophagy, apoptosis, the cell cycle, viability, metastasis, and chemotherapy sensitivity. [43][44][45][46] In the present study, we demonstrated that miR-665 directly targets HMGB1 and inactivates the Wnt/β-catenin pathway to inhibit the various malignant behaviors of RB in vitro and in vivo.…”

High-mobility group protein�B1 silencing promotes susceptibility of retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear factor-κB

“…Moreover, the expression of HMGB1 was higher in tumors with poor differentiation and optic nerve invasion (16). In addition, numerous studies demonstrated that HMGB1 was associated with cancer resistance to chemotherapy.…”

“…HMGB1 had been reported to be overexpressed in several cancers, including RB, and it is closely correlated with tumorigenesis and tumor development. Singh et al found that HMGB1 was expressed in 55.07% (38̸69) primary RB cases through immunohistochemistry, and HMGB1 mRNA expression was observed in 77.41% (24̸31) fresh tumor tissue samples via reverse transcription-polymerase chain reaction analysis (16).…”

Expression of High-Mobility Group Box 1 Protein (HMGB1) and Toll-Like Receptor 9 (TLR9) in Retinas of Diabetic Rats

“…It serves as a damage-associated molecular pattern (DAMP) and mediates various physical or pathological processes, including inflammatory cytokine release, cell migration, and angiogenesis, mainly through TLR2, TLR4, and RAGE [13–15]. Thus, it has been demonstrated to be a late mediator of infection involved in the pathogenesis of autoimmunity [16], cancer [17], trauma [18], and IR injury [19]. Indeed, as a DAMP molecule, HMGB1 is receiving increasing DR research attention [20].…”