Stem cell-ness: a "magic marker" for cancer

Abstract

Transcriptional profiling of patient tumors is a much-heralded advancement in cancer therapy, as it provides the opportunity to identify patients who would benefit from more or less aggressive therapy and thus allows the development of individualized treatment. However, translation of this promise into patient benefit has proven challenging. In this issue of the JCI, Glinsky and colleagues used human and murine models to identify a potential stem cell mRNA signature, based on the hypothesis that tumors with stem cell-like characteristics are likely to have a poor prognosis (see the related article beginning on page 1503). Remarkably, an 11-gene "expression signature" associated with "stem cell-ness" separated patients with different cancers into good-and poor-prognosis groups. Such a "magic marker" would, if validated, have a major impact on patient care. However, there remain challenges incumbent with creating and validating such signatures.Nonstandard abbreviations used: ANK3, ankyrin 3; Bmi-1, murine leukemia viral-1; BUB1, budding uninhibited by benzimidazoles 1; CCNB1, cyclin B1; CES, carboxylesterase; FGFR2, FGF receptor 2; GBX2, gastrulation homeobox 2; HCFC1, host cell factor c1; Ki-67, antigen identified by mAb ki-67; KNTC2, kinetochore-associated 2; PNS, peripheral nervous system; RNF2, ring finger 2; SPAI, stem cell-like phenotype association index; TRAMP, transgenic adenocarcinoma of the mouse prostate; USP22, ubiquitin-specific protease 22.

ALDH1 Is a Marker of Normal and Malignant Human Mammary Stem Cells and a Predictor of Poor Clinical Outcome

“…The detection of an ALDH1-positive population in TMA cores may be due to an increased self-renewal activity in these tumors. A recent study has shown that a gene expression signature associated with increased self-renewal of normal stem cells is a predictor of poor prognosis (Glinsky et al, 2005;Lahad et al, 2005). In agreement with our findings, previously described molecular signatures of breast cancer associated with a poor prognosis for breast cancer contain one or more ALDH isotypes (Alexe et al, 2006).…”

Independent prognostic value of the basal‐like phenotype of breast cancer and associations with EGFR and candidate stem cell marker BMI‐1

“…This might serve to delineate different differentiation pathways, rather than attribute ‘stemness’ to all positive tumour cells. As stem cell markers have been associated with a more primitive phenotype, tumour cell expression could indicate de‐differentiation, and thus possible increased aggressiveness 65,66 . Whereas haematological malignancies are related to a well‐characterized hierarchy of putative precursor cells, such a structure is only just emerging with regard to epithelial tumours.…”

Carcinogenesis and environment: the cancer stem cell hypothesis and implications for the development of novel therapeutics and diagnostics

“…So far, tumor markers are associated with differentiated stages of cancer cells, such as the prostate-specific antigen (PSA) (60,61) and CA125 (62), which are prognostic antigens for prostate and ovarian cancer, respectively. An exciting recent study focused on the proto-oncogene Bmi-1 (63,64), which belongs to the polycomb group gene family (65). Bmi-1 plays a primary role in the self-renewal of adult hematopoietic stem cells (66) and neuronal stem cells (67).…”