Challenging, Accurate and Feasible: CAF-1 as a Tumour Proliferation Marker of Diagnostic and Prognostic Value

Abstract

The discovery of novel biomarkers of diagnostic, prognostic, and therapeutic value is a major challenge of current cancer research. The assessment of tumour cell proliferative capacity is pivotal for grading and clinical decision-making, highlighting the importance of proliferation markers as diagnostic and prognostic tools. Currently, the immunohistochemical analysis of Ki-67 expression levels is routinely used in clinical settings to assess tumour proliferation. Inasmuch as the function of Ki-67 is not fully understood and its evaluation lacks standardization, there is interest in chromatin regulator proteins as alternative proliferation markers of clinical value. Here, we review recent evidence demonstrating that chromatin assembly factor 1 (CAF-1), a histone chaperone selectively expressed in cycling cells, is a proliferation marker of clinical value. CAF-1 expression, when evaluated by immunocytochemistry in breast cancer cytology smears and immunohistochemistry in cancer biopsies from several tissues, strongly correlates with the expression of Ki-67 and other proliferation markers. Notably, CAF-1 expression is upregulated in almost all cancers, and CAF-1 overexpression is significantly associated, in most cancer types, with high histological tumour grade, advanced stage, recurrence, metastasis, and decreased patient survival. These findings suggest that CAF-1 is a robust, reproducible, and feasible proliferation marker of prognostic importance. CAF-1 may represent an attractive alternative or complementary to Ki-67 for cancer stratification and clinical guidance.

Histone Chaperones and Digestive Cancer: A Review of the Literature

“…CAF-1 functions as a histone chaperone that assembles newly synthesized histone H3/H4 onto replicating DNA [ 112 ]. Therefore, CAF-1 is essential for DNA replication during the process of nucleosome formation, as well as chromatin recovery after DNA repair [ 113 ].…”

Overexpression of CHAF1A is associated with poor prognosis, tumor immunosuppressive microenvironment and treatment resistance

“…CAF-1, an outstanding marker of proliferating cell ( Polo et al, 2004 ), has been found to be the key regulator in DNA replication and chromatin restoration ( Zheng et al, 2018 ). The expression of CAF-1 is positively correlated with the expression of Ki-67 in cancers ( Sykaras et al, 2021 ).…”

Overexpression of CHAF1A correlates with poor prognosis and tumor immunosuppressive microenvironment and resistance to treatment in cancer

“…CAF-1, an outstanding marker of proliferating cell [3], has been found to be the key regulator in DNA replication and chromatin restoration [4]. The expression of CAF-1 is positively correlated with the expression of Ki-67 in cancers [5].…”

“…CAF-1 is a nuclear complex containing three subunits in human cells, CHAF1A (p150), CHAF1B (p60), and RBBP4 (p48) [5]. Among the three subunits, CHAF1A is the major one and plays essential role in CAF-1 complex [6,7].…”