Introduction: Introduction:
Despite advances in detection and treatment, cancer remains a main public health crisis across the globe [1]. It was estimated that in 2024, 2 million new cancer cases would be diagnosed in the worldwide, along with over 600,000 estimated deaths [2].Although cancer diagnosis and therapy have been improved gradually, the survival of patients remains poor, which are mainly affected by drug resistance, local recurrence, and development of metastatic disease. [3] According to the research studies, cancer stem cells (CSCs) with the principal properties of multipotency and self-renewal are responsible for neoplasm formation, metastasis, recurrence, and therapeutic resistance. [4-7] Cancer stem cells were successfully isolated and identified in many hematologic tumors including colorectal cancer, glioblastoma, cholangiocarcinoma, ovarian cancer, hepatocellular carcinoma, Osteosarcoma. [8] Numerous of molecules have been investigated as putative markers of CSCs. Among the different markers, CD133 is one of the most robust surface marker of CSCs. [9] it is widely expressed in numerous types of tumors, involving colorectal, Lung and ovarian cancer. [10] It is a 5 transmembrane single-chain glycoprotein, with a molecular weight of 120 kDa, which was first found to be expressed in hematopoietic stem and progenitor cells. [11] Based on the recent studies CD133+ cells in Cancer had the ability to initiate tumor growth. The paradigm of CD133 as a CSCs biomarker has stimulated many studies to explore the prognostic power of CD133 expression in patients. However, the prognostic value of CD133 for different type of cancers remain controversial despite of numerous independent studies. We performed a meta-analysis to determine the value of CD133 as a prognostic marker for all type of cancer and a robust target for cancer treatment.
Methods: Search Strategy and Selection Criteria:
We searched PubMed, EMBASE, Elsevier databases MEDLINE (PubMed), Google Scholar, Web of Science (Thomson-Reuters) with Medical Subject Heading keywords CD133, CSCs, Prominin, Cancer therapy, examining the CD133 as a CSC marker for targeting cancer therapy published up to August 15, 2024. In addition, we reviewed citations in the retrieved articles to search for additional relevant studies. Searches were limited to papers published in English only. Studies were included in the meta-analysis, if they included patients with Cancer diagnosis by pathologists according to the American Association guidelines; data on CD133 (Prominin) marker and full-length papers; and data about odds ratios (ORs) with 95% confidence intervals (CI), or at least adequate data to calculate 95% CIs. The following studies were excluded; overlapping articles or duplicate data; review articles and conference records without original data and full text; to investigate the effects of targeting CD133 marker of CSC in varieties of cancer types.
Inclusion and exclusion criteria:
Studies were selected according to the following inclusion criteria: (1) full-text published studies up August 15, 2024; (2) a case-control or a Clinical Trial design; (3) the study goal was to evaluate the effect of CD133 marker as a significant marker for cancer therapy. (4) Sufficient data for estimating 95% confidence interval (CI) and odds ratio (OR).
Data extraction:
In this study Information was extracted from all the eligible studies independently by 2 researchers using a pre-designed form according to the selection criteria listed above. For each study the following information was extracted: the name of first author, publication year, country where the study was conducted, racial descent, type of cancer, cancer treatment testing method, number of patients and the final effect of targeting cancer therapy.
Results: Result:
13 records were found after examining online databases, references, and related articles; 7 of these records were subsequently eliminated as being unrelated. The current meta-analysis also included 6 eligible study. Table 1 provides basic data, including, the number of patients, results, effect, method, country and year.
According to the results of this investigation, CD133 plays prominent roles in different cancer types and is responsible for cancer recurrence and metastasis and is a promising marker for cancer treatment.
Table1: the results of targeting CD133 as cancer treatment.
Patient Results Effect Method Country Year
21 Longer overall survival promising antitumor activity CD133-directed chimeric antigen receptor (CAR) T (CART-133) China 2020
38 Longer overall survival increased sensitivity to cisplatin trial of metformin as a cancer stem cell–targeting agent USA 2020
52 feasible treatment remarkable shrinkage or even disappearance of some metastases Cocktail treatment with EGFR-specific andCD133-specific chimeric antigen receptor-modified T cells China 2017
2 therapeutic effect on cancer cells decrease of CD133 expression MicroRNA-133a Expression Profiles Japan 2013
21 Longer survival and no evidence of tumor recurrence decrease in or absence of CD133 expression multi-epitope-pulsed dendritic cell vaccine USA 2012
33 No difference in CD133 mRNA expression CD133 mRNA expression did not change significantly Protein Kinase C B-Inhibitor Enzastaurin in Combination with Gemcitabine and Cisplatin USA 2007
Conclusion: CSCs can be distinguished by their properties of self-renewal and differentiation and subsequently generate cancer cells. Several studies have examined effect of targeting CD133 as a CSCs marker for cancer treatment in different cancer types; but the results were controversial. Meta-analysis has been recognized as a prominent tool to exactly define the effect of targeting different CSC markers for cancer therapy. The present meta-analysis was carried out by critically reviewing 6 relevant and new recently published studies on targeting CD133 for cancer treatment. Hence, it may provide more information. The overall effects of these 6 clinical studies (Table1) suggest CD133 as a promise marker for treatment.