New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

Masciale, Valentina; Banchelli, Federico; Grisendi, Giulia; D’Amico, Roberto; Maiorana, Antonino; Stefani, Alessandro; Morandi, Uliano; Dominici, Massimo; Aramini, Beatrice

doi:10.3389/fonc.2021.613198

Cited by 12 publications

(20 citation statements)

References 75 publications

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“…It is difficult to interpret this observation at this point, given the lack of information about CSCs broadly, but we believe there are important steps and differences not yet investigated in CSCs at early vs locally advanced stages. This idea is strongly supported by our recently published article 62 regarding the presence of overexpressed cell-cycle genes linked to recurrence in both early and locally advanced stages, which may suggest that CSCs are in a “state of quiescence” in the early stages but become activated in locally advanced disease. More studies need to be done in the future to confirm and develop this hypothesis.…”

Section: Discussionmentioning

confidence: 68%

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

Masciale

Banchelli

Grisendi

et al. 2022

Stem Cells Translational Medicine

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Purpose Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL). Experimental design This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis. Results Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25). Conclusion No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages. Clinical Trial Registration NCT04634630.

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Section: Discussionmentioning

confidence: 68%

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

Masciale

Banchelli

Grisendi

et al. 2022

Stem Cells Translational Medicine

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“…Furthermore, CSCs’ genomic information is used to analyze tissue biopsies [ 28 , 135 ]. The authors identified and isolated CSCs via fluorescent-activated cell sorting (FACS) to investigate cell behavior in vitro and gene expression from the surgical tumor tissue of 22 NSCLC patients [ 136 ].…”

Section: Cancer Resistance: Cscs and The Tumor Microenvironmentmentioning

confidence: 99%

“…To better understand the role of a previously validated cell cycle gene signature associated with cancer recurrence [ 136 ], Masciale et al isolated CSCs from fresh surgical lung cancer specimens by isolating ALDH high + cells [ 28 , 136 ]. It should be noted that ALDH is not only a marker but a functional regulator of CSCs.…”

Section: Cscs As Novel Targets For Cancer Therapy: New Perspectives T...mentioning

confidence: 99%

“…Beyond the urge to find a surface marker, and beside the fact that several publications have shown the presence of stemness genes in CSCs, new strategies are being carried out, specifically targeting the activity of cancer stem cells, in particular on a CSC gene signature [ 136 ]. A cross-sectional study involving 22 patients undergoing surgery for adenocarcinoma or squamous cell carcinoma of the lung investigated a huge and already known panel of 31 cell-cycle genes related to cancer recurrence, for both early and locally advanced stages, to create more tailored therapies in the future [ 136 ]. The novelty of this recently published cross-sectional study was in identifying the same recurrence of genes in CSCs for early and locally advanced stages.…”

Section: Cscs As Novel Targets For Cancer Therapy: New Perspectives T...mentioning

confidence: 99%

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Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

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Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

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“…In this study, we investigated the relationship between smoking and lung cancer in silico, hoping to further elucidate their relationship. Genetic changes play an important role in lung cancer [ 23 ]. Notably, gene expression changes have been reported in the lung cancer tissues of smokers and nonsmokers with lung adenocarcinoma [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Long Noncoding RNAs in Smoking-Induced Lung Cancer: An In Silico Study

Zhao

Sun

et al. 2022

Computational and Mathematical Methods in Medicine

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The prevalence of lung cancer induced by cigarette smoking has increased over time. Long noncoding (lnc) RNAs, regulatory factors that play a role in human diseases, are commonly dysregulated in lung cancer. Cigarette smoking is closely related to changes in lncRNA expression, which can affect lung cancer. Herein, we assess the mechanism of lung cancer initiation induced by smoking. To calculate the impact of smoking on the survival of patients with lung cancer, we extracted data from The Cancer Genome Atlas and Gene Expression Omnibus databases and identified the differentially expressed genes in the lung cancer tissue compared to the normal lung tissue. Genes positively and negatively associated with smoking were identified. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape analyses were performed to determine the function of the genes and the effects of smoking on the immune microenvironment. lncRNAs corresponding to smoking-associated genes were identified, and a smoking-related lncRNA model was constructed using univariate and multivariate Cox analyses. This model was used to assess the survival of and potential risk in patients who smoked. During screening, 562 differentially expressed genes were identified, and we elucidated that smoking affected the survival of patients 4.5 years after the diagnosis of lung cancer. Furthermore, genes negatively associated with smoking were closely associated with immunity. Twelve immune cell types were also found to infiltrate differentially in smokers and nonsmokers. Thus, the smoking-associated lncRNA model is a good predictor of survival and risk in smokers and may be used as an independent prognostic factor for lung cancer.

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New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

Cited by 12 publications

References 75 publications

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Role of Long Noncoding RNAs in Smoking-Induced Lung Cancer: An In Silico Study

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