Evaluation of aldehyde dehydrogenase 1 (ALDH1) as a marker of non-small cell lung cancer (NSCLC) stem cells (SCs) and correlation with prognosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11105-11105
Author(s):  
R. Zhou ◽  
Q. Liu ◽  
N. W. Todd ◽  
J. Deepak ◽  
Z. Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Early Stage ◽  
Chemotherapeutic Agents ◽  
Cancer Specific Survival ◽  
Early Stage Nsclc ◽  
Aldh1 Expression ◽  
Aldefluor Assay ◽  
Nsclc Patients

11105 Background: ALDH1 is a cytosolic enzyme responsible for oxidizing intracellular aldehydes, and conversion of retinol to retinoic acid in SCs. ALDH1 has been previously demonstrated to be a marker for SCs in breast cancer (Ginestier C, et al., Cell Stem Cell. 2007 Nov; 1(5):555–67). The Aldefluor assay is based on conversion of a synthetic substrate BAAA, when passively infused into cytosol, to brightly fluorescent BAA by ALDH1. Combined with fluorescence-activated cell sorting (FACS), it has been used successfully in hematopoietic and breast cancer SCs isolation. ALDH1 is also found in NSCLC. We hypothesized that ALDH1 would be a marker for NSCLC SCs and a potential prognostic marker. Methods: NSCLC SCs were isolated from human NSCLC cell lines using the Aldefluor assay and FACS. ALDH1-positive cells were analyzed extensively for SC characteristics. ALDH1 expression in 303 NSCLC biopsy specimens from three independent cohorts of NSCLC patients was then analyzed by immunohistochemisty (IHC) using an ALDH1 antibody (Santa Cruz Biotechnology) and commercially available negative controls. Results: Isolated cancer cells with high ALDH1 activity displayed cancer SCs features, including capacities for proliferation, self-renewal, differentiation; resistance to chemotherapeutic agents including cisplatin, vinorelbine, gemcitabine and docetaxel; expression of the SC surface marker CD133, and high invasiveness. ALDH1-positive cells generated tumors in vivo recapitulating heterogeneity of parental cells. Xenograft tumors derived from ALDH1-positive cells (103 each) were 36±2.9 mm3 on average in size, with some of the cells having lost ALDH1 expression. Xenograft tumors derived from ALDH1-negative cells (105 each) were 4 mm3 on average in size, without ALDH1 reactivation. Statistical analysis of quantitative IHC and clinical data showed ALDH1 expression was correlated with higher stage and grade of NSCLC (p = 0.02). Expression of ALDH1 in stage I NSCLC patients was linked to decreased 5 year cancer-specific survival (62% vs. 96%, p = 0.006) and overall survival (32% vs. 72%, p = 0.009). Conclusions: 1. ALDH1 is a NSCLC SC-associated tumor marker. 2. ALDH1 expression is a negative prognostic marker in early stage NSCLC. No significant financial relationships to disclose.

scholarly journals Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Biological Characteristics ◽  
Cancer Specific Survival ◽  
Age Related ◽  
Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

PD-0418: Dose on cardiac (sub)structures as predictor for OS in early stage NSCLC patients treated with SBRT

2020 ◽  
Vol 152 ◽  
pp. S226-S227
Author(s):  
M. Duijm ◽  
D. Pezzulla ◽  
W. Schillemans ◽  
J. Nuyttens
Keyword(s):  
Early Stage ◽  
Early Stage Nsclc ◽  
Nsclc Patients

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2660-2667 ◽  
Author(s):  
Yen-Tsung Huang ◽  
Rebecca S. Heist ◽  
Lucian R. Chirieac ◽  
Xihong Lin ◽  
Vidar Skaug ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Massachusetts General Hospital ◽  
Early Stage ◽  
The United States ◽  
Small Cell ◽  
Genome Wide Analysis ◽  
Early Stage Nsclc ◽  
Genome Wide ◽  
Nsclc Patients

Purpose Lung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. Patients and Methods One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Results Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend = 3.80 × 10−12 and 2.48 × 10−7 for MGH and Norwegian cohorts, respectively). Conclusion Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

scholarly journals Application of green synthesized WO3-poly glutamic acid nanobiocomposite for early stage biosensing of breast cancer using electrochemical approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Nasrollahpour ◽  
Abdolhossein Naseri ◽  
Mohammad-Reza Rashidi ◽  
Balal Khalilzadeh
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Electrochemical Biosensor ◽  
Early Stage ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Electrochemical Approach ◽  
Her 2

AbstractBiopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients.

scholarly journals P2.04-04 CITEseq Characterization in Early Stage NSCLC Patients Identifies Distinct Patterns of Immune Infiltrate

2019 ◽  
Vol 14 (10) ◽  
pp. S708-S709
Author(s):  
A. Leader ◽  
B. Maier ◽  
J. Grout ◽  
C. Chang ◽  
L. Walker ◽  
...  
Keyword(s):  
Early Stage ◽  
Immune Infiltrate ◽  
Early Stage Nsclc ◽  
Nsclc Patients
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