Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Guida, Florence; Sun, Nan; Bantis, Leonidas E.; Muller, David C.; Li, Peng; Taguchi, Ayumu; Dhillon, Dilsher; Kundnani, Deepali L.; Patel, Nikul; Yan, Qingxiang; Byrnes, Graham; Moons, Karel G.M.; Tjønneland, Anne; Panico, Salvatore; Agnoli, Claudia; Víneis, Paolo; Palli, Domenico; Bueno‐de‐Mesquita, Bas; Peeters, Petra H.M.; Agudo, Antonio; Huerta, José María; Dorronsoro, Miren; Rodriguez‐Barranco, Miguel; Ardanáz, Eva; Travis, Ruth C.; Smith-Byrne, Karl; Boeing, Heiner; Steffen, Annika; Kaaks, Rudolf; Hüsing, Anika; Trichopoulou, Antonia; Λάγιου, Παγώνα; Vecchia, Carlo La; Severi, Gianluca; Boutron‐Ruault, Marie‐Christine; Sandanger, Torkjel M.; Weiderpass, Elisabete; Nøst, Therese Haugdahl; Tsilidis, Kostas; Riboli, Elio; Grankvist, Kjell; Johansson, Mikael; Goodman, Gary E.; Feng, Ziding; Brennan, Paul; Johansson, Mattias; Hanash, Samir M.

doi:10.1001/jamaoncol.2018.2078

Cited by 109 publications

(93 citation statements)

References 16 publications

(30 reference statements)

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“…Luminex analyses of fresh blood samples also revealed that of three previously established biomarkers of lung cancer risk, i.e., CEA, CA125, CYFRA 21-1 19 , only CEA was higher in smokers. Interestingly, Pearson correlation analyses (Table 2) revealed that CEA levels correlated with monocyte (R = 0.463) and granulocyte (R = 0.505) numbers.…”

Section: Discussionmentioning

confidence: 64%

“…As well, since a panel of biomarkers consisting of CEA, CA125, CYFRA 21-1 and Pro-SFTPB was recently found to be highly predictive of smokers subsequently developing lung cancer 19 , we were interested in determining their values. We did not test SFTPB, however, since there were no commercially available kits and it had been reported that SFTPB has a non-linear, J-shaped association with lung cancer risk (with no and high levels increasing risk), making interpretation of results difficult 23 .…”

Section: Resultsmentioning

confidence: 99%

“…developed lung cancer were found, in a recent study, to have elevated levels of 4 proteins, cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1) and the precursor form of surfactant protein B (Pro-SFTPB), suggesting this panel of biomarkers might be highly useful for smokinginduced lung cancer risk assessment 19 .…”

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confidence: 99%

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The effect of smoking on chronic inflammation, immune function and blood cell composition

Elisia

Lam

Cho

et al. 2020

Sci Rep

108

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Smoking is the number one risk factor for cancer mortality but only 15–20% of heavy smokers develop lung cancer. It would, therefore, be of great benefit to identify those at high risk early on so that preventative measures can be initiated. To investigate this, we evaluated the effects of smoking on inflammatory markers, innate and adaptive immune responses to bacterial and viral challenges and blood cell composition. We found that plasma samples from 30 heavy smokers (16 men and 14 women) had significantly higher CRP, fibrinogen, IL-6 and CEA levels than 36 non-smoking controls. Whole blood samples from smokers, incubated for 7 h at 37 °C in the absence of any exogenous stimuli, secreted significantly higher levels of IL-8 and a number of other cytokines/chemokines than non-smokers. When challenged for 7 h with E. coli, whole blood samples from smokers secreted significantly lower levels of many inflammatory cytokines/chemokines. However, when stimulated with HSV-1, significantly higher levels of both PGE2 and many cytokines/chemokines were secreted from smokers’ blood samples than from controls. In terms of blood cell composition, red blood cells, hematocrits, hemoglobin levels, MCV, MCH, MCHC, Pct and RDW levels were all elevated in smokers, in keeping with their compromised lung capacity. As well, total leukocytes were significantly higher, driven by increases in granulocytes and monocytes. In addition, smokers had lower NK cells and higher Tregs than controls, suggesting that smoking may reduce the ability to kill nascent tumor cells. Importantly, there was substantial person-to person variation amongst smokers with some showing markedly different values from controls and others showing normal levels of many parameters measured, indicating the former may be at significantly higher risk of developing lung cancer.

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Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

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The effect of smoking on chronic inflammation, immune function and blood cell composition

Elisia

Lam

Cho

et al. 2020

Sci Rep

108

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“…Integrated classifiers have also been explored in terms of plasma protein biomarkers such as the ones tested by some panel components in our cohort (25).…”

Section: Discussionmentioning

confidence: 99%

Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers

Xie

X²,

et al. 2018

Preprint

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BACKGROUND Early detection of lung cancer to allow curative treatment remains challenging.Cell-free circulating tumor DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. METHODS The multi-center clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white blood cell genomic DNA (gDNA) and tumor tissue gDNA of each patient were analyzed by ultra-deep sequencing to an average of 35,000X of the coding regions of 65 lung cancer-related genes.RESULTS The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients is at Stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%.When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for Stage I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harbored mutations in the lung cancer patients with the largest number found in TP53 (30% plasma and 62% tumor tissue samples) and EGFR (20% and 40%, respectively).CONCLUSION Plasma ctDNA was analyzed in lung nodule assessment and early cancer detection while an algorithm combining clinical information enhanced the test performance.

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“…Another study detected a combined panel of circulating tumour DNA fragments and tumour-related proteins: 59% of newly diagnosed lung-cancer cases were uncovered with high specificity, but lower sensitivity for early-stage cancers [ 67 ]. More recently, a risk-prediction model based on smoking history and immunodetection of four protein markers (cancer antigen 125, carcinoembryonic antigen, cytokeratin-19 fragment, and precursor of surfactant protein B) in US cohorts was found to outperform a smoking-history-only model when applied to pre-diagnostic samples from two European cohorts [ 68 ]. At a fixed specificity of 0.83 based on the screening criteria of the United States Preventive Services Task Force (USPSTF), the model based on smoking-plus-biomarker had a sensitivity for screening eligibility of 0.63 vs. 0.42 for the smoking-based model alone.…”

Section: Eligibly Criteria For Ldct-lcsmentioning

confidence: 99%

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

Veronesi

Baldwin

Henschke

et al. 2020

Cancers

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Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached.

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Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Abstract: This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

Cited by 109 publications

References 16 publications

The effect of smoking on chronic inflammation, immune function and blood cell composition

The effect of smoking on chronic inflammation, immune function and blood cell composition

Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

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