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Cancers
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New Insight of Non-small Cell Lung Cancer
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New Insight of Non-small Cell Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 20156

Special Issue Editor

Dr. Nobuyuki Horita

E-Mail Website
Guest Editor
Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Interests: meta-analysis; systematic review; surrogate outcome; NSCLC; SCLC; immune checkpoint inhibitor

Special Issue Information

Dear Colleagues,

Non-small cell lung cancer is currently the most common malignant neoplasm in the world and the leading cause of cancer deaths worldwide. In more than half of the cases, non-small cell lung cancer is detected after the disease has already progressed. For these patients, chemotherapy is usually the first-line treatment. Traditionally, several platinum-based drugs have been used as the standard first-line treatment for non-small cell lung cancer. However, the development of molecular targeted therapies and immune checkpoint inhibitors has dramatically changed the treatment of non-small cell lung cancer. In addition to early-stage diseases, radiotherapy and surgery are also indicated for advanced diseases with certain conditions. In addition, comorbidities such as interstitial lung disease and metastatic lesions require careful consideration to select treatment option. In this Special Issue, we would like to discuss recent topics related to non-small cell lung cancer.

Dr. Nobuyuki Horita
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • non-small cell lung carcinoma
  • biomarkers
  • immune checkpoint inhibitors
  • randomized controlled trial
  • evidence-based medicine
  • co-morbidities

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Published Papers (7 papers)

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Research

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12 pages, 1734 KiB  
Article
Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer
by Amelia Acha-Sagredo, Cornelia M. Wilson, Naiara Garcia Bediaga, Helen Kalirai, Michael P. A. Davies, Sarah E. Coupland, John K. Field and Triantafillos Liloglou
Cancers 2024, 16(11), 2154; https://doi.org/10.3390/cancers16112154 - 6 Jun 2024
Viewed by 1300
Abstract
Sortilin is an important regulator with potential tumour-suppressor function by limiting EGFR signalling. In this study, we undertook a comprehensive expression analysis of sortilin transcript variants and the DNA methylation status of their corresponding promoters in human non-small cell carcinomas (NSCLCs). RNA/DNA was [...] Read more.
Sortilin is an important regulator with potential tumour-suppressor function by limiting EGFR signalling. In this study, we undertook a comprehensive expression analysis of sortilin transcript variants and the DNA methylation status of their corresponding promoters in human non-small cell carcinomas (NSCLCs). RNA/DNA was extracted from 81 NSCLC samples and paired normal tissue. mRNA expression was measured by qPCR and DNA methylation determined by pyrosequencing. BigDye-terminator sequencing was used to confirm exon-8 alternative splicing. Results demonstrated that both SORT1A and SORT1B variants were downregulated in lung tumours. The SORT1A/SORT1B expression ratio was higher in tumours compared to normal tissue. SORT1B promoter hypermethylation was detected in lung tumours compared to normal lung (median difference 14%, Mann–Whitney test p = 10−6). Interestingly, SORT1B is hypermethylated in white blood cells, but a small and very consistent drop in methylation (6%, p = 10−15) was observed in the lung cancer cases compared to control subjects. We demonstrate that the SORT1B exon-8 splice variation, reported in sequence databases, is also a feature of SORT1A. The significantly altered quantitative and qualitative characteristics of sortilin mRNA in NSCLC indicate a significant involvement in tumour pathogenesis and may have significant impact for its utility as a predictive marker in lung cancer management. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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16 pages, 2184 KiB  
Article
Tailoring Therapeutic Strategies in Non-Small-Cell Lung Cancer: The Role of Genetic Mutations and Programmed Death Ligand-1 Expression in Survival Outcomes
by Nobuaki Kobayashi, Kenji Miura, Ayami Kaneko, Hiromi Matsumoto, Kohei Somekawa, Tomofumi Hirose, Yukihito Kajita, Anna Tanaka, Shuhei Teranishi, Yu Sairenji, Hidetoshi Kawashima, Kentaro Yumoto, Toshinori Tsukahara, Nobuhiko Fukuda, Ryuichi Nishihira, Makoto Kudo, Naoki Miyazawa and Takeshi Kaneko
Cancers 2023, 15(21), 5248; https://doi.org/10.3390/cancers15215248 - 31 Oct 2023
Cited by 1 | Viewed by 1596
Abstract
Background: This study aims to assess the real-world impact of advancements in first-line systemic therapies for non-small-cell lung cancer (NSCLC), focusing on the role of driver gene mutations and programmed death-ligand 1 (PD-L1) expression levels. Methods: Conducted across eight medical facilities in Japan, [...] Read more.
Background: This study aims to assess the real-world impact of advancements in first-line systemic therapies for non-small-cell lung cancer (NSCLC), focusing on the role of driver gene mutations and programmed death-ligand 1 (PD-L1) expression levels. Methods: Conducted across eight medical facilities in Japan, this multicenter, retrospective observational research included 863 patients diagnosed with NSCLC and treated between January 2015 and December 2022. The patients were categorized based on the type of systemic therapy received: cytotoxic agents, molecular targeting agents, immune checkpoint inhibitors, and combination therapies. Comprehensive molecular and immunohistochemical analyses were conducted, and statistical evaluations were performed. Results: The median overall survival (OS) shows significant variations among treatment groups, with targeted therapies demonstrating the longest OS. This study also revealed that high PD-L1 expression was common in the group treated with immune checkpoint inhibitors. Multivariate analysis was used to identify the type of anticancer drug and the expression of PD-L1 at diagnosis as the impactful variables affecting 5-year OS. Conclusions: This study underscores the efficacy of targeted therapies and the critical role of comprehensive molecular diagnostics and PD-L1 expression in affecting OS in NSCLC patients, advocating for their integration into routine clinical practice. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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22 pages, 5283 KiB  
Article
PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype
by Stefano Lucà, Renato Franco, Antonella Napolitano, Valeria Soria, Andrea Ronchi, Federica Zito Marino, Carminia Maria Della Corte, Floriana Morgillo, Alfonso Fiorelli, Antonio Luciano, Giuseppe Palma, Claudio Arra, Sabrina Battista, Laura Cerchia and Monica Fedele
Cancers 2023, 15(7), 2190; https://doi.org/10.3390/cancers15072190 - 6 Apr 2023
Cited by 6 | Viewed by 2786
Abstract
Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its [...] Read more.
Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure. Here we investigated expression and role of PATZ1 in NSCLC, in correlation with NSCLC subtypes and PD-L1 expression. A cohort of 104 NSCLCs, including lung squamous cell carcinomas (LUSCs) and adenocarcinomas (LUADs), was retrospectively analyzed by immunohistochemistry for the expression of PATZ1 and PD-L1. The results were correlated with each other and with the clinical characteristics, showing on the one hand a positive correlation between the high expression of PATZ1 and the LUSC subtype and, on the other hand, a negative correlation between PATZ1 and PD-L1, validated at the mRNA level in independent NSCLC datasets. Consistently, two NSCLC cell lines transfected with a PATZ1-overexpressing plasmid showed PD-L1 downregulation, suggesting a role for PATZ1 in the negative regulation of PD-L1. We also showed that PATZ1 overexpression inhibits NSCLC cell proliferation, migration, and invasion, and that Patz1-knockout mice develop LUAD. Overall, this suggests that PATZ1 may act as a tumor suppressor in NSCLC. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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14 pages, 1892 KiB  
Article
Visceral Obesity in Non-Small Cell Lung Cancer
by Lindsay Nitsche, Yeshwanth Vedire, Eric Kannisto, Xiaolong Wang, Robert J. Seager, Sarabjot Pabla, Santosh K. Patnaik and Sai Yendamuri
Cancers 2022, 14(14), 3450; https://doi.org/10.3390/cancers14143450 - 15 Jul 2022
Cited by 3 | Viewed by 2059
Abstract
While obesity measured by body mass index (BMI) has been paradoxically associated with reduced risk and better outcome for lung cancer, recent studies suggest that the harm of obesity becomes apparent when measured as visceral adiposity. However, the prevalence of visceral obesity and [...] Read more.
While obesity measured by body mass index (BMI) has been paradoxically associated with reduced risk and better outcome for lung cancer, recent studies suggest that the harm of obesity becomes apparent when measured as visceral adiposity. However, the prevalence of visceral obesity and its associations with demographic and tumor features are not established. We therefore conducted an observational study of visceral obesity in 994 non-small cell lung cancer (NSCLC) patients treated during 2008–2020 at our institution. Routine computerized tomography (CT) images of the patients, obtained within a year of tumor resection or biopsy, were used to measure cross-sectional abdominal fat areas. Important aspects of the measurement approach such as inter-observer variability and time stability were examined. Visceral obesity was semi-quantified as visceral fat index (VFI), the fraction of fat area that was visceral. VFI was found to be higher in males compared to females, and in former compared to current or never smokers. There was no association of VFI with tumor histology or stage. A gene expression-based measure of tumor immunogenicity was negatively associated with VFI but had no bearing with BMI. Visceral obesity is appraisable in routine CT and can be an important correlate in lung cancer studies. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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20 pages, 3873 KiB  
Article
Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma
by Joseph C. Tsai, Omar A. Saad, Shruti Magesh, Jingyue Xu, Abby C. Lee, Wei Tse Li, Jaideep Chakladar, Mark M. Fuster, Eric Y. Chang, Jessica Wang-Rodriguez and Weg M. Ongkeko
Cancers 2021, 13(16), 4225; https://doi.org/10.3390/cancers13164225 - 23 Aug 2021
Cited by 5 | Viewed by 3466
Abstract
Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA [...] Read more.
Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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Review

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17 pages, 349 KiB  
Review
Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives
by Mathieu Césaire, Juliette Montanari, Hubert Curcio, Delphine Lerouge, Radj Gervais, Pierre Demontrond, Jacques Balosso and François Chevalier
Cancers 2022, 14(12), 2829; https://doi.org/10.3390/cancers14122829 - 8 Jun 2022
Cited by 26 | Viewed by 2751
Abstract
Survival in unresectable locally advanced stage non-small cell lung cancer (NSCLC) patients remains poor despite chemoradiotherapy. Recently, adjuvant immunotherapy improved survival for these patients but we are still far from curing most of the patients with only a 57% survival remaining at 3 [...] Read more.
Survival in unresectable locally advanced stage non-small cell lung cancer (NSCLC) patients remains poor despite chemoradiotherapy. Recently, adjuvant immunotherapy improved survival for these patients but we are still far from curing most of the patients with only a 57% survival remaining at 3 years. This poor survival is due to the resistance to chemoradiotherapy, local relapses, and distant relapses. Several biological mechanisms have been found to be involved in the chemoradioresistance such as cancer stem cells, cancer mutation status, or the immune system. New drugs to overcome this radioresistance in NSCLCs have been investigated such as radiosensitizer treatments or immunotherapies. Different modalities of radiotherapy have also been investigated to improve efficacity such as dose escalation or proton irradiations. In this review, we focused on biological mechanisms such as the cancer stem cells, the cancer mutations, the antitumor immune response in the first part, then we explored some strategies to overcome this radioresistance in stage III NSCLCs with new drugs or radiotherapy modalities. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
12 pages, 257 KiB  
Review
Current Treatment Strategies for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia
by Satoshi Ikeda, Terufumi Kato, Hirotsugu Kenmotsu, Akimasa Sekine, Tomohisa Baba and Takashi Ogura
Cancers 2021, 13(16), 3979; https://doi.org/10.3390/cancers13163979 - 6 Aug 2021
Cited by 11 | Viewed by 4391
Abstract
Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP [...] Read more.
Of patients with advanced non-small-cell lung cancer (NSCLC), 5–10% have interstitial pneumonia (IP) at the time of diagnosis. To avoid fatal acute exacerbations of pre-existing IP, appropriate patient selection and low-risk treatment choices are warranted. Risk factors for acute exacerbation of pre-existing IP with cytotoxic drugs include honeycomb lungs on computed tomography (CT) and low forced vital capacity, but risk factors with immune checkpoint inhibitors (ICIs) have not been fully investigated. For advanced or recurrent NSCLC with comorbid IP, carboplatin plus nanoparticle albumin-bound paclitaxel is the standard of care for first-line treatment, but second-line or later treatment has not been established. ICI holds great promise for long-term survival, but many challenges remain, including safety and appropriate patient selection. Since the indications for pharmacotherapy and radiotherapy for NSCLC with comorbid IP are quite limited, surgical resection should be considered as much as possible for patients with operable stages. A scoring system has been reported to predict the risk of postoperative acute exacerbation of pre-existing IP, but perioperative treatment has not been established. In the future, it is necessary to accumulate more cases and conduct further research, not only in Japan but also worldwide. Full article
(This article belongs to the Special Issue New Insight of Non-small Cell Lung Cancer)
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