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

Abstract

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.

Unbiased peptoid combinatorial cell screen identifies plectin protein as a potential biomarker for lung cancer stem cells

“…CD133 expression was higher only in PCS2-bead-bound H1693 cells and undetectable in all three remaining cell lines. It is known that the expression of two lung CSC biomarkers ALDH and CD133 do not correlate 21,24,25 , and we did not detect CD133 expression in either the PCS2 bound or the unbound fractions of H358, H460, and H1975 NSCLCs (Fig. 2B–E).…”

TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21–IL-4 pathway in lung adenocarcinoma

“…Previous studies reported that CSC biomarkers such as NANOG [ 21 , 22 ], OCT4 [ 21 , 23 ], SOX2 [ 21 , 24 ], KLF4 [ 21 , 25 ] and ALDH1A1 [ 21 , 26 ] were associated with a poor prognosis in several cancers. The correlation analysis indicated that the average expression of the five cancer stemness biomarkers was tightly associated with TBX21 in the integrated GEO dataset ( r ≥ 0.850, P < 0.05; Fig.…”

Ti0.8O2Nanosheets Inhibit Lung Cancer Stem Cells by Inducing Production of Superoxide Anion

“…CSC-targeted therapy and treatment strategies are urgently needed. CSCs can be recognized by their specific markers, such as ALDH1A1 and CD133, (Miyata et al, 2017) and by their cellular traits, such as colony formation and other aggressive behaviors (Yongsanguanchai et al, 2015;Tiran et al, 2017).…”