Cytoplasmic levels of high mobility group A2 determine survival prognoses in breast cancer patients

Abstract

Background: High mobility group A proteins are involved in chromatin remodeling, thereby influencing multiple fundamental biological processes. HMGA2 has been linked to oncogenic traits among a variety of malignancies. Objective: To determine the prognostic implications of subcellular distribution patterns of HMGA2 in breast cancer. Methods: Nuclear and cytoplasmic HMGA2 was evaluated in 342 breast cancer specimens and matched with clinico-pathological parameters. Results: Overall and cytoplasmic, but not nuclear, levels of HMGA2 correlated with better survival prognoses in our collective (hazard ratio (HR) 0.34, P = 0.001 and HR 0.34, P < 0.001, respectively). The protective effect of cytoplasmic HMGA2 persisted in the Luminal A and triple negative breast cancer subgroups. Evaluating Luminal A and B subgroups jointly, only cytoplasmic, but not overall or nuclear HMGA2 levels were associated with better survival (HR 0.42, 95% confidence interval 0.21, 0.86, P = 0.017), irrespective of tumor size and node status. The addition of HMGA2 overall and cytoplasmic scores strengthened the prognostic selectivity in a model of conventional breast cancer risk factors. No predictive significance with regard to endocrine or chemoendocrine therapies was observed. Conclusion: Unexpectedly, we found a favorable survival probability upon overall levels of HMGA2 in our breast cancer collective, which was predominantly determined by the presence of HMGA2 in the cytoplasm.

Prognostic significance of high mobility group A2 (HMGA2) in pancreatic ductal adenocarcinoma: malignant functions of cytoplasmic HMGA2 expression

“…Western blot results revealed an unmistakable detectability of HMGA2 in cytoplasmic cell lysates. Cytoplasmic HMGA2 has been also found by others in various tumor entities (Abe et al 2003;Rahman et al 2009;Gong et al 2019;Heilmann et al 2020).…”

“…Western blot results revealed an unmistakable detectability of HMGA2 in cytoplasmic cell lysates. Cytoplasmic HMGA2 has been also found by others in various tumor entities (Abe et al 2003 ; Rahman et al 2009 ; Gong et al 2019 ; Heilmann et al 2020 ). Noteworthy, yet, to the best of our knowledge, there are no reports analyzing the clinical relevance of the intracellular distribution of HMGA2 in PDAC.…”

“…Heilmann et al described cytoplasmic HMGA2 as an autonomous phenomenon with a prognostic effect in breast cancer patients. High levels of cytoplasmic HMGA2 were associated with a favorable overall survival of breast cancer patients (Heilmann et al 2020 ). However, the mechanism of how cytoplasmic HMGA2 favors patient survival needs further investigations.…”

“…However, our recent report on HMGA2 in breast cancer clearly revealed a prognostic significance of cytoplasmic HMGA2. In particular, high levels of cytoplasmatic HMGA2 were associated with a favorable overall survival of breast cancer patients (Heilmann et al 2020 ). In detail, HMGA2 expression was linked to better survival in triple negative breast cancer and well-differentiated estrogen receptor-positive breast cancer patients irrespective of lymph node metastases or tumor size.…”