| 1. |
- Feng, Xiaoshuang, et al.
(författare)
-
Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis.Methods: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only.Findings: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10–1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61–0.66), compared with 0.62 (95% CI: 0.59–0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: −0.003 to 0.035).Interpretation: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information.
|
|
| 2. |
- Feng, Xiaoshuang, et al.
(författare)
-
Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
|
|
| 3. |
- Huang, Joyce Y., et al.
(författare)
-
Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
- 2020
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
|
|
| 4. |
- Midttun, Oivind, et al.
(författare)
-
Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations
- 2017
-
Ingår i: American Journal of Clinical Nutrition. - : AMER SOC NUTRITION-ASN. - 0002-9165 .- 1938-3207. ; 105:6, s. 1314-1326
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and a-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
|
|
| 5. |
- Theofylaktopoulou, Despoina, et al.
(författare)
-
Impaired functional vitamin B6 status is associated with increased risk of lung cancer
- 2018
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:12, s. 2425-2434
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
|
|
