Ki67 is a promising molecular target in the diagnosis of cancer (Review)

Abstract

The expression of Ki67 is strongly associated with tumor cell proliferation and growth, and is widely used in routine pathological investigation as a proliferation marker. The nuclear protein Ki67 (pKi67) is an established prognostic and predictive indicator for the assessment of biopsies from patients with cancer. Clinically, pKi67 has been shown to correlate with metastasis and the clinical stage of tumors. In addition, it has been shown that Ki67 expression is significantly higher malignant tissues with poorly differentiated tumor cells, as compared with normal tissue. According to its predictive role, pKi67 expression identifies subpopulations of patients who are more likely to respond to a given therapy. The Ki67 labeling index is an independent prognostic factor for survival rate, which includes all stages and grade categories. There is a correlation between the ratio of Ki67‑positive malignant cells and patient survival. It has been shown that blocking of Ki67 either by microinjection of antibodies or through the use of antisense oligonucleotides leads to the arrest of cell proliferation. Specifically, antisense oligonucleotides and antibodies against pKi67 have been shown to inhibit the progression of the cell cycle. The Ki67 protein is well characterized at the molecular level and is extensively used as a prognostic and predictive marker for cancer diagnosis and treatment. Increasing evidence indicates that Ki67 may be an effective target in cancer therapy. It therefore merits further development, including testing in more sophisticated in vitro and appropriate in vivo models. This review provides an overview of recent advances in this field.

HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous RNA mechanism

“…We found that the expression of several genes were influenced by HMGA1P7 including also genes involved in cancer progression such as Col6a3, Mki67, H19, Igf2, Gpx3 and Leprel1 3031323334353637. Indeed, oncomine analyses and tissue-microarray immunohistochemistry showed overexpression of COL6A3 in colorectal carcinomas that was significantly and directly correlated with Dukes stage, T stage, stage, recurrence and smoking status and then with a poor prognosis30.…”

“…1, the quantitative qRT-PCR analyses confirmed the data obtained from the RNA-seq analyses. Interestingly, these genes have been related to several human cancers (colon, gastric, liver, breast and hematological cancers), and are considered possible therapeutic targets303132333435.…”

Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ

“…Among these proteins, the widely used proliferation markers Mk167 (Ki67) and Top2␣ [23,24] and the nuclear targeted mitogen Hdgf [25,26] were all induced by PFOS exposure, as determined by iTRAQ assay and confirmed by western blot assay. These data suggest that PFOS probably stimulated HL-7702 proliferation under the experimental conditions.…”

Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer

“…After 26 days of EgKI-1 treatment there was ~60% reduction of tumor growth in treated mice compared with controls. As Ki67 expression is strongly associated with tumor cell proliferation [30], the significantly decreased numbers of Ki67-positive cells in tumor tissues treated with EgKI-1 reflect its inhibitory effect on cell proliferation in vivo .…”

“…Ki67 is a nuclear protein that is expressed in proliferating cells and is thus a marker for cell proliferation in solid tumors [30]. Ki67 stained slides were then scanned at 20× magnification with an Aperio Scanscope XT slidescanner and digital images were analyzed with ImageScope viewing software.…”