Is CD133 Expression a Prognostic Biomarker of Non-Small-Cell Lung Cancer? A Systematic Review and Meta-Analysis

Wu, Hong; Qi, Xiaowei; Yan, Guangning; Zhang, Qingbi; Xu, Chuan; Bian, Xiu‐Wu

doi:10.1371/journal.pone.0100168

Cited by 36 publications

(30 citation statements)

References 29 publications

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“…In previous studies, the expression of CD133 was correlated with a poor prognosis in lung cancer (24). Similarly to other reports (24,25), our analysis indicated that CD133-positive tumors were associated with significantly worse outcomes in comparison to CD133-negative tumors. We therefore consider CD133 to be an appropriate CSC marker.…”

Section: Discussionsupporting

confidence: 88%

“…Although several landmark studies have revealed that isolated CD133-positive lung cancer cells exhibited in vitro CSC-like features and in vivo tumorigenicity, subsequent studies showed similar tumorigenic potential of both CD133-positive and CD133-negative lung cancer cells both in vitro and in vivo (6,23). In previous studies, the expression of CD133 was correlated with a poor prognosis in lung cancer (24). Similarly to other reports (24,25), our analysis indicated that CD133-positive tumors were associated with significantly worse outcomes in comparison to CD133-negative tumors.…”

Section: Discussionmentioning

confidence: 97%

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The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

Miyata

Oyama

Yoshimatsu

et al. 2017

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Abstract. Background/Aim: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCsDespite continuous efforts to improve therapeutic response, lung cancer is the most common cause of cancer-related deaths in Japan, with adenocarcinoma by far the most common histology, accounting for nearly 70% of lung cancer cases (1). Cancer stem cells (CSCs) have the ability for selfrenewal and multipotently differentiate (2). CSCs may be highly resistant to chemotherapy and radiation, and be responsible for tumor initiation, progression and metastasis (3, 4). Accumulating evidence supports the existence of a CSC phenotype in human lung cancer (3, 5-7). The metabolic marker aldehyde dehydrogenase isoform 1A1 (ALDH1A1) and the cell-surface marker CD133 are reported to be markers of lung CSCs (3). We, therefore, investigated ALDH1A1 and CD133 expression in a retrospective cohort of 92 patients with lung adenocarcinoma. The objectives were to determine the association between ALDH1A1 and CD133 expression in lung adenocarcinoma, the relationship between their expression and the clinichopathological parameters, and the prognostic value of ALDH1A1 and CD133. Materials and MethodsPatient population and clinicopathological data. We examined a series of 154 Japanese patients with lung adenocarcinoma who underwent surgical treatment at Fukuoka-Wajiro Hospital, Fukuoka, Japan from 2006-2012. Ninety-two out of 154 (59.7%) patients were selected based on the following inclusion criteria: (i) no chemotherapy or radiotherapy before surgery, and (ii) the availability of an adequate paraffin block and clinicopathological data for the analysis. Follow-up information was obtained from the patients' records. Routinely collected clinicopathological data included age, gender, smoking history and pathological stage. There were 49 males (53%) and 43 females (47%), with a median age of 71 years (range=40-92 years) at the time of surgery; 43 (47%) patients were <70 years and 49 (53%) were ≥70 years of age. Half of the patients (n=46) had a smoking history. The pathological stages were: stage I, n=62 (67.4%); stage II, n=14 (15.2%); stage III, n=12 (13.0%); and stage IV, n=4 (4.4%) (TNM staging of lung cancer) (8). The median follow-up period was 1,702 days (range=4-3679 days). Recurrence was diagnosed by computed tomography alone or combined with positron-emission tomography.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 97%

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

Miyata

Oyama

Yoshimatsu

et al. 2017

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“…Accumulating evidence indicated a presence of the high protein levels of CD133 in numerous types of cancer. The highly expressed CD133 predicts poor outcomes of cancer patients of ovarian cancer, colorectal cancer, prostate cancer, rectal cancer, lung cancer, and glioblastoma (Horst et al, 2009b, Merlos-Suarez et al, 2011, Ong et al, 2010, Silva et al, 2011, Artells et al, 2010, Hurt et al, 2008, Saigusa et al, 2009, Zeppernick et al, 2008, Zhang et al, 2008, Alamgeer et al, 2013, Huang et al, 2015, Wu et al, 2014). This is because cancer cells that express high levels of CD133 are more metastatic and resistant to chemotherapy and radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

CD133 as a regulator of cancer metastasis through the cancer stem cells

Liou

2019

The International Journal of Biochemistry & Cell Biology

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Cancer stem cells are the cancer cells that have abilities to self-renew, differentiate into defined progenies, and initiate and maintain tumor growth. They also contribute to cancer metastasis and therapeutic resistance, both of which are the major causes of cancer mortality. Among the reported makers of the cancer stem cells, CD133 is the most well-known marker for isolating and studying cancer stem cells in different types of cancer. The CD133high population of cancer cells are not only capable of self-renewal, proliferation, but also highly metastatic and resistant to therapy. Despite very limited information on physiological functions of CD133, many ongoing studies are aimed to reveal the mechanisms that CD133 utilizes to modulate cancer dissemination and drug resistance with a long-term goal for bringing down the number of cancer deaths. In this review, in addition to the regulation of CD133, and its involvement in cancer initiation, and development, the recent updates on how CD133 modulates cancer dissemination, and therapeutic resistance are provided. The key signaling pathways that are upstream or downstream of CD133 during these processes are summarized. A comprehensive understanding of CD133-mediated cancer initiation, development, and dissemination through its pivotal role in cancer stem cells will offer new strategies in cancer therapy.

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“…Inhibition of CD133ϩve NSCLC Tumor Cells Invasion in Vitro following Activation of D 2 DA Receptors-As expression of CD133 in NSCLC tumor cells correlates with invasion and metastasis in lymph nodes (25), we therefore investigated whether D 2 DA receptor activation in these CD133ϩve tumor cells in NSCLC has any effect on invasiveness of these cells. In our in vitro experiment, both the concentrations of quinpirole (1 M and 10 M) significantly inhibited the invasion of CD133ϩve NSCLC tumor cells through the Matrigel (Fig.…”

Section: Down-regulation Of Oct-4 Expression In Cd133ϩve Nsclcmentioning

confidence: 99%

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells

Roy

Nayak

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangLung carcinoma is the leading cause of cancer-related death worldwide, and among this cancer, non-small cell lung carcinoma (NSCLC) comprises the majority of cases. Globally, lung cancers are considered to be the leading causes of cancer-related deaths, and non-small cell lung carcinoma (NSCLC) 4 is the predominant type of lung cancer, occurring in 85% of the cases (1, 2). The prognosis of NSCLC is poor, and the survival rate is only 15% after 5 years because many of these patients ultimately do not respond to chemotherapy and radiotherapy due to the presence of CSC (3-5). The CSC have the unique ability to promote tumor growth, recurrence, metastasis, and resistance to treatment (6, 7).Moreover, CD133, a surface glycoprotein with a five-transmembrane domain, has been widely used as a surface marker to identify CSC in many human tumors including NSCLC (8 -12). Although CD133 is expressed in various human tissues, its glycosylated epitopes specific for stem cells may be discordant or sometimes absent, making it difficult to identify this cell population (13). There may be transcriptional or post-translational modifications (14), leading to some degree of alteration in its expression, or variation in its expression in different tumors may be due to the use of antibodies from different clones (12). However, despite these limitations, recent results from different laboratories have shown significant association of CD133 (epitope-1) expression in a population of tumor cells with CSC characteristics in the brain, prostate, liver, and lung (15-18).There are now several reports that have further strengthened the concept of CD133ϩve tumor cells as CSC in NSCLC as these tumor cells possess the characteristics of CSC (18 -20). In contrast to the CD133Ϫve tumor cells, CD133ϩve tumor cells are more tumorigenic and resistant to radiation and anticancer drugs (18 -20). These cells also have a greater ability to form anchorage-independent floating spheres, proliferation, and tumor mass than the CD133Ϫve NSCLC cells. The CD133ϩve cells like CSC demonstrate significantly increased stemness, adhesion, motility, and expression of drug efflux gene (21-23) than CD133Ϫve tumor cells. Importantly, the presence of CD133ϩve tumor cells correlates well with poor prognosis, decreased survival, and increased lymph node metastasis in NSCLC patients (24 -26).Furthermore, in addition to CD133, aldehyde dehydrogenase 1 (ALDH1) is also used as a CSC marker in NSCLC (12,(27)(28)(29)(30) 4 The abbreviations used are: NSCLC, non-small cell lung carcinoma; CSC, cancer stem cell(s); D 2 DA, D 2 dopamine (DA) receptors; ERK1/2, extracellular signal-regulated kinases 1/2; MMP-9, matrix metalloproteinase-9; MTT, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide; PI, propidium iodide.

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Is CD133 Expression a Prognostic Biomarker of Non-Small-Cell Lung Cancer? A Systematic Review and Meta-Analysis

Cited by 36 publications

References 29 publications

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

CD133 as a regulator of cancer metastasis through the cancer stem cells

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells

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