Increased levels of <scp>microRNA</scp>‐320 in blood serum and plasma is associated with imminent and advanced lung cancer

Nøst, Therese Haugdahl; Skogholt, Anne Heidi; Urbárová, Ilona; Mjelle, Robin; Paulsen, Erna-Elise; Dønnem, Tom; Andersen, Sigve; Markaki, Maria; Røe, Oluf Dimitri; Johansson, Mikael; Grønberg, Bjørn Henning; Sandanger, Torkjel M.; Sætrom, Pål

doi:10.1002/1878-0261.13336

Cited by 4 publications

(3 citation statements)

References 62 publications

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“…The miR-320 family has previously been linked to metastatic lung cancer, suggesting that alterations in serum levels of miR-320 could be secondary effects due to systemic immune responses in patients. [ 11 ]. Future studies that concurrently measure systemic immune responses and miRNA levels in serum could potentially clarify these associations and provide functional insights into altered serum miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients

Mjelle,

Kristensen,

Tora S. Solheim

et al. 2024

Mol Cancer

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Metastatic colorectal cancer (mCRC) presents significant challenges in clinical management due to its heterogeneity and variable response to treatment. In this study, we conducted comprehensive small RNA (sRNA) sequencing analyses to identify sRNA biomarkers associated with survival and treatment response in mCRC patients. We measured serum sRNAs before and after chemotherapy treatment in a discovery cohort of 189 mCRC patients. Our analysis revealed 25 microRNAs (miRNA) as significantly associated with overall survival at baseline. We found that 11 of the 25 significant miRNAs were also significant in an independent validation cohort of 20 mCRC patients, including the top five miRNAs from the discovery cohort. Importantly, all but four of the 25 significant miRNAs from the discovery cohort had hazard ratios in the same direction in the validation cohort. Among the 25 significant miRNAs, we identified the miR-320 family of miRNAs as the strongest independent prognostic marker, with high baseline levels correlating with poor survival outcomes. Furthermore, post-treatment levels of the same miRNAs were even more predictive of overall survival, emphasizing the prognostic value of serum changes in miRNA levels before and after treatment. Moreover, we observed significant changes in serum miRNAs and other sRNAs when comparing samples before and after chemotherapy, with distinct expression patterns between responders and non-responders. Leveraging these differential expression patterns, we established a serum sRNA signature that accurately predicts response to chemotherapy with an area under the curve (AUC) of 0.8. In summary, our study highlights the prognostic and predictive potential of sRNA biomarkers in mCRC, offering valuable insights into patient stratification and personalized treatment approaches.

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Section: Discussionmentioning

confidence: 99%

Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients

Mjelle,

Kristensen,

Tora S. Solheim

et al. 2024

Mol Cancer

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“…Additionally, other bioinformatical analyses available during analyses will be considered. miRNA expression will be analysed by standardised bioinformatics pipelines as previously described 26. The limma and voom linear modelling framework27 will identify miRNAs with treatment-related longitudinal expression changes.…”

Section: Methodsmentioning

confidence: 99%

“…miRNA expression will be analysed by standardised bioinformatics pipelines as previously described. 26 The limma and voom linear modelling framework 27 will identify miRNAs with treatment-related longitudinal expression changes. Additionally, other bioinformatical analyses available during analyses will be considered.…”

Section: Methodsmentioning

confidence: 99%

Randomised controlled trial of exercise training during lactation on breast milk composition in breastfeeding people with overweight/obesity: a study protocol for the MILKSHAKE trial

Moholdt,

Ashby,

Tømmerdal

et al. 2023

BMJ Open Sport Exerc Med

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Breast milk from people with overweight/obesity may differ in composition compared with that from normal-weight people. Exercise training can modify breast milk composition in rodent models, with a beneficial impact demonstrated on the offspring’s metabolism, but whether these findings translate to humans is unclear. This trial aims to determine the effect of an exercise intervention on breast milk composition and whether an exercise-induced modification of breast milk impacts the infants’ growth and body composition. Effect of Exercise Training on Breastmilk Composition is a randomised, controlled trial with two parallel groups, one exercise group and one control group, with a 1:1 allocation. We will include a minimum of 62 exclusively breastfeeding participants, 6 weeks postpartum. The exercise intervention lasts 8 weeks and comprises 25 supervised endurance exercise sessions with moderate or high intensity. The primary outcome measure is the change in the relative concentration of the human milk oligosaccharide 3′sialyllactose in breast milk from baseline at 6 weeks postpartum to the end of the intervention period. Secondary outcomes include breast milk concentrations of other metabolites, cytokines, hormones and microRNA, maternal health outcomes, infant growth, infant gut microbiome and infant circulating microRNA. Maternal and infant outcomes will be measured before, during and after the intervention period, with a follow-up of the infants until they are 24 months old. Trial registration numberNCT05488964.

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Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study

Fotopoulos,

Nguyen,

Nøst

et al. 2024

J Cancer Res Clin Oncol

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Introduction Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis. Methods Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0–8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated. Results Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples. Conclusion There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed.

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Increased levels of microRNA‐320 in blood serum and plasma is associated with imminent and advanced lung cancer

Cited by 4 publications

References 62 publications

Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients

Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients

Randomised controlled trial of exercise training during lactation on breast milk composition in breastfeeding people with overweight/obesity: a study protocol for the MILKSHAKE trial

Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study

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