Identification Of Cancer Stem Cells Markers Research Articles

Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review.

Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood cancers. They exhibit a high tendency to develop early metastases and are often resistant to available treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021 was retrieved from different databases, of which 35 articles were included for analysis. The studies demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the identification of CSC markers in sarcomas may facilitate the development of personalized medicine and improve treatment outcomes.

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma.

Targeting cancer stem cells (CSC) may represent a future therapeutic direction for osteosarcoma (OS), which mainly relies on the identification of CSC markers. This study aimed to classify OS based on messenger ribonucleic acid (mRNA) stemness indices (mRNAsi) and construct a mRNAsi-related risk model to predict the prognosis of OS. The one-class logistic regression (OCLR) algorithm was applied to the RNA- sequencing (seq) data of human embryonic stem cells (hESC) and induced pluripotent stem cell (iPSC) lines to calculate mRNAsi. Weighted gene co-expression network analysis (WGCNA) was performed on data obtained from the TARGET database to screen the mRNAsi-related genes. Univariate Cox regression analysis was implemented to screen mRNAsi-related genes with prognostic significance for consensus clustering of OS. The least absolute shrinkage and selection operator (LASSO) and COX regression analysis were conducted to construct a risk model based on mRNAsi-related genes. Six gene modules were identified in the TARGET database. The yellow module showed the strongest negative correlation with mRNAsi and the strongest significant positive correlation with the immune score and stromal score. OS was divided into three molecular subtypes with significant survival differences based on 73 mRNAsi-related genes with prognostic value for OS. The survival rate was ranked as C3 < C1 < C2 from low to high. The levels of immune components in C2 was significantly higher than those in C1 and C3. HSD11B2, GBP1, RNF130, APBB1IP, and NPC2 in the yellow module were used as variables for building the mRNAsi-related risk model. The survival rate of the high-risk group (as defined by this model) was significantly higher than that of the low-risk group, and it had significant survival prediction ability in 28 types of cancer. In addition, the mRNAsi-related risk model was superior to the Tumor Immune Dysfunction and Exclusion (TIDE) model in predicting the prognosis and immunotherapy response in all three immunotherapy cohorts. This study classified OS and constructed a mRNAsi-related risk model based on mRNAsi-related genes, which provides a potential tool for more accurate risk stratification of OS and prediction of immunotherapy response.

Cancer stem cell characteristics and their potential as therapeutic targets.

Cancer stem cells (CSCs) are a tumour subpopulation whose capacity for self-renewal, differentiation and proliferation generates unfavourable patient outcomes, including therapeutic resistance and metastasis. Much research has focused on the generation, biomarkers and therapeutic resistance of CSCs, as well as the development of CSC-targeted therapies. Reviews to date have either addressed general CSC characteristics or focused on CSCs from a well-studied cancer. Increasingly, specific treatment plans based on identification of molecular features and biomarkers of a patient's cancer, rather than classification according to tissue origin or bulk tumour properties, are leading to better patient outcomes. Here, we compare CSC characteristics, specifically their biomarkers and molecular features, and identify those that are common to a number of cancers. Identification of CSC markers that suggest therapeutic strategies has led to several successful in vitro and animal tests, recommending clinical trials of treatments with potentially enhanced therapeutic benefits, especially for recurring cancers.

Abstract 1405: Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis

Abstract Purpose: Cancer stem cells (CSCs) are responsible for cancer progression, metastasis, and recurrence. The identification of CSC markers may open a new therapeutic perspective on the basis of selectively targeting this small population of cancer cells, however, the specific markers of CSCs remain undiscovered. The aim of this study was to identify novel biomarkers of gastric CSCs for clinical diagnosis using proteomics technology. Materials and Methods: Since the side population (SP) cells of gastric cancer possess CSC-like properties, we used CSC-like SP cells, OCUM-12/SP cells and OCUM-2MD3/SP cells in this study. Their parent OCUM-12 cells and OCUM-2MD3 cells were also used. Protein lysates from each cell line were analyzed using QSTAR Elite Liquid Chromatography with Tandem Mass Spectrometry, coupled with isobaric tags for relative and absolute quantitation technology. Proteins overexpressed in SP cells were determined by comparing the proteomes among parent cells and CSC-like SP cells. Candidate proteins detected by proteomics technology were validated by RT-PCR, western blot, invasion assay, and immunohistochemical analysis of 300 gastric cancers. Results: Based on the results of LC-MS/MS, eight proteins, including RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, were up-regulated in both OCUM-12/SP cells and OCUM-2MD3/SP cells when compared to their corresponding parent cells. RT-PCR analysis indicated that the expression level of RBBP6, HSPA4, DCTPP1, HSPA9, VPS13A, ALDOA, GLG1, and CK18 was high in OCUM-12/SP and OCUM-2MD3/SP, in compared with the control of parent OCUM-12 and OCUM-2MD3. These proteins were significantly associated with advanced invasion depth, lymph node metastasis, distant metastasis, or advanced clinical stage. RBBP6, DCTPP1, HSPA4, and ALDOA expression in particular were significantly associated with a poor prognosis in the 300 gastric cancer patients. RBBP6 was determined to be an independent prognostic factor. The motility-stimulating ability of OCUM-12/SP cells and OCUM-2MD3/SP cells was inhibited by RBBP6 siRNA. Conclusion: The eight proteins, RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, utilizing comparative proteomics analysis, were perceived to be potential CSC markers of gastric cancer. Of the eight candidate proteins, RBBP6 was suggested to be a promising prognostic biomarker and a therapeutic target for gastric cancer. Citation Format: Masakazu Yashiro, Tamami Morisaki, Tsuyoshi Hasegawa, Anna Kakehashi, Haruhito Kinoshita, Tatsunari Fukuoka, Hiroaki Kasashima, Go Masuda, Katsunobu Sakurai, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Hideki Wanibuchi, Kosei Hirakawa. Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1405. doi:10.1158/1538-7445.AM2015-1405

Complementary and Alternative Medicine in Cancer Stem Cells

Cancer stem cells (CSCs), a small subpopulation of cancer cells prone to form tumorigenesis, resemble normal stem cells with self-renewal and differentiation characteristics. CSCs have recently been identified in leukemia and various types of solid tumors. There is growing evidence indicating that CSCs might be the principal cause for the development of resistance to cancer treatments, recurrence, and metastasis. Emerging data indicates that CSCs and normal stem cells may share cellular pathways regulating proliferation and differentiation. These pathways include, but not limited to, polycomb group transcriptional repressor Bmi-1, Notch, Sonic hedgehog, and Wnt pathways. Therefore, identification of CSC markers, selection and development of unique therapeutics targeting CSCs and related signaling pathways have been extensively investigated. In this special issue, we publish articles that explore aspects of complementary and alternative medicine (CAM) associated with CSCs in basic research, in translational medicine, and in clinical application for cancer treatment. The topic will highlight current research, encourage additional research, draw attention to the subject, and ultimately help advance the field of CAM application in CSCs.

C-Met in pancreatic cancer stem cells: Therapeutic implications

Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths. Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease. The identification of CSC markers could lead to the development of new therapeutic targets. In this study, the authors explore the functional role of c-Met in pancreatic CSCs, by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice. They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Met(high) in a higher tumorigenic cancer cell population. Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs. In pancreatic tumors established in NOD SCID mice, c-Met inhibition slowed tumor growth and reduced the population of CSCs, along with preventing the development of metastases.

Cancer Stem Cells in Breast Cancer

The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities. In this review, we focus on recent reports regarding the identification of CSC markers and the molecular mechanism of CSC phenotypes to understand the basic properties and molecular target of CSCs. In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease. The identification of CSC markers and an improved understanding of the molecular mechanism of CSC phenotypes should lead to progress in cancer therapy and improved prognoses for patients with cancer.