Analysis of the characteristics and prognosis of advanced non-small-cell lung cancer in older patients

Gao, Ying; Gao, Fei; Ma, Jin-lu; Zhang, Xiaozhi; Li, Yi; Song, Liping; Zhao, Dongfang

doi:10.2147/ppa.s87069

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…The mutational landscape present in a cancer genome is the cumulative result of endogenous and/or exogenous mutational processes (e.g., smoking), constant or sporadic and with different strengths along patient ageing [ 4 – 7 ]. Therefore, multiple mutational processes are operative resulting in jumbled composite signatures and tumor characteristics vary between patients of different ages [ 7 – 9 ]. From the Catalogue Of Somatic Mutations In Cancer (COSMIC) which includes 10,952 exomes and 1,048 whole-genomes across 40 distinct types of human cancer [ 10 ], 30 different mutational signatures were identified and publicly released ( http://cancer.sanger.ac.uk/cosmic/signatures ).…”

Section: Introductionmentioning

confidence: 99%

Somatic genome alterations in relation to age in lung squamous cell carcinoma

et al. 2018

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Lung squamous cell carcinoma (LUSC) is the most common cause of global cancer-related mortality and the major risk factors is smoking consumption. By analyzing ∼500 LUSC samples from The Cancer Genome Atlas, we detected a higher mutational burden as well as a higher level of methylation changes in younger patients. The SNPs mutational profiling showed enrichments of smoking-related signature 4 and defective DNA mismatch repair (MMR)-related signature 6 in younger patients, while the defective DNA MMR signature 26 was enriched among older patients. Furthermore, gene set enrichment analysis was performed in order to explore functional effect of somatic alterations in relation to patient age. Extracellular Matrix-Receptor Interaction, Nucleotide Excision Repair and Axon Guidance seem crucial disrupted pathways in younger patients. We hypothesize that a higher sensitivity to smoking-related damages and the enrichment of defective DNA MMR related mutations may contribute to the higher mutational burden of younger patients. The two distinct age-related defective DNA MMR signatures 6 and 26 might be crucial mutational patterns in LUSC tumorigenesis which may develop distinct phenotypes. Our study provides indications of age-dependent differences in mutational backgrounds (SNPs and CNVs) as well as epigenetic patterns that might be relevant for age adjusted treatment approaches.

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Section: Introductionmentioning

confidence: 99%

Somatic genome alterations in relation to age in lung squamous cell carcinoma

et al. 2018

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“…On the other hand, in China, the estimated mortality of lung cancer is higher than the world average (2), which may be related to the neglect of early finding and diagnosis. It is reported that approximately two-thirds of patients are diagnosed at the advanced stage (3,4). During the past 5 years, a rising Chinese population, especially people in East China, is covered by medical insurance and routine physical examinations.…”

Section: Introductionmentioning

confidence: 99%

Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011–2015

Wang

Jixia

et al. 2017

J. Thorac. Dis.

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Background: More than one-third of lung cancer worldwide occurring in China. However, the clinical profiles of lung cancer patients in the mainland of China are rarely reported and largely unknown. The Results: From 2011 to 2015, aggregately 5,779 patients, including 3,719 males and 2,060 females, were diagnosed as lung cancer. The major histologic subtypes of lung cancer were adenocarcinoma (ADC, 60.0%), squamous cell carcinoma (SCC, 25.6%), small cell lung cancer (SCLC, 8.5%), large cell carcinoma (0.6%), adenosquamous carcinoma (1%), other non-small cell carcinoma (1.6%) and unclassified or rare carcinoma (2.8%). ADC proportion of female was much higher than that of male. A higher proportion of advanced stage (stage IIIB, IV) of lung cancer existed in patients who were admitted to hospital due to respiratory or cancer related symptoms (RCRS) than those without RCRS. Smoking rate in male patients reached 80.2%, while it was only 2.7% in females. EGFR mutation existed in 66% of female and 37% of male patients with ADC.Conclusions: This study demonstrates the clinicopathologic characteristics of lung cancer patients from East China, including histologic composition, staging proportion, smoking prevalence and gene mutation status. During the past 5 years, the proportion of ADC has increased gradually whereas SCC decreased.

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“…Our present study found altered amino acid profiles in AML after both ATRA and valproic acid treatment, and we observed a considerable heterogeneity in pretherapy metabolite levels among AML patients when comparing (i) responders versus non-responders and (ii) non-responders with rapidly progressive disease versus other non-responders. The mechanisms behind altered amino acid profiles in cancer patients may be related to the risk of cancer [65] or reflect nutritional or microbiotic alterations, progression of the disease, cachexia or weight loss [66,67,68]. In our opinion, it is most likely that the mechanism behind the differences in amino acid metabolism between various AML patient groups is also multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Systemic Metabolomic Profiling of Acute Myeloid Leukemia Patients before and During Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid, Valproic Acid, and Low-Dose Chemotherapy

Grønningsæter

Fredly

Gjertsen

et al. 2019

Cells

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Acute myeloid leukemia (AML) is an aggressive malignancy, and many elderly/unfit patients cannot receive intensive and potentially curative therapy. These patients receive low-toxicity disease-stabilizing treatment. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid can stabilize the disease for a subset of such patients. We performed untargeted serum metabolomic profiling for 44 AML patients receiving treatment based on ATRA and valproic acid combined with low-dose cytotoxic drugs (cytarabine, hydroxyurea, 6-mercaptopurin) which identified 886 metabolites. When comparing pretreatment samples from responders and non-responders, metabolites mainly belonging to amino acid and lipid (i.e., fatty acid) pathways were altered. Furthermore, patients with rapidly progressive disease showed an extensively altered lipid metabolism. Both ATRA and valproic acid monotherapy also altered the amino acid and lipid metabolite profiles; however, these changes were only highly significant for valproic acid treatment. Twenty-three metabolites were significantly altered by seven-day valproic acid treatment (p < 0.05, q < 0.05), where the majority of altered metabolites belonged to lipid (especially fatty acid metabolism) and amino acid pathways, including several carnitines. These metabolomic effects, and especially the effects on lipid metabolism, may be important for the antileukemic and epigenetic effects of this treatment.

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Analysis of the characteristics and prognosis of advanced non-small-cell lung cancer in older patients

Cited by 6 publications

References 31 publications

Somatic genome alterations in relation to age in lung squamous cell carcinoma

Somatic genome alterations in relation to age in lung squamous cell carcinoma

Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011–2015

Systemic Metabolomic Profiling of Acute Myeloid Leukemia Patients before and During Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid, Valproic Acid, and Low-Dose Chemotherapy

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