HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma-not otherwise specified

Abstract

Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma-not otherwise specified (IDC-NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC-NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC-NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC-NOS were detected using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1-positive, and 100 out of 148 (67.6%) were ER-positive. Of the latter, 28% (28/100) were HPK1-positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=−0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC-NOS tissues were PR- or HER2-positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor-node-metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER-positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC-NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC-NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.

Hematopoietic Progenitor Kinase 1 in Tumor Immunology: A Medicinal Chemistry Perspective

“…However, the direct relationship between HPK1 expression and immune response needs further study. Nevertheless, HPK1 may be a new effective therapeutic target for IDC-NOS for further study …”

“…Nevertheless, HPK1 may be a new effective therapeutic target for IDC-NOS for further study. 84 HPK1 is expressed in normal pancreatic ductal cells, but is absent in pancreatic ductal adenocarcinoma (PDAC). HPK1 is known to act as a negative feedback regulator of T cells, or as a regulator of the MAPK/ERK pathway.…”

Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer

“…For example, Hematopoietic Progenitor Kinase-1 (HPK1) is a member of the MAP4K family expressed largely in hematopoietic cells [78], and acts upstream of MAPK signaling [79]. HPK1 has been reported to regulate both nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and activates JNK signaling pathway [80], and is associated with progression of gastrointestinal tumors [81]. The roles of HPK1 in T-cell function is now becoming clear.…”

MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway

“…Furthermore, Wang, J., et, al. reported that HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma [11]. MAP4K1 affected cell-cycle progression and mediated Vitamin D resistance in AML cell lines [12].…”