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Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value.

Walker MJ, Zhou C, Backen A, Pernemalm M, Williamson AJ, Priest LJ, Koh P, Faivre-Finn C, Blackhall FH, Dive C, Whetton AD - EBioMedicine (2015)

Bottom Line: Identification of such markers would allow treatment options to be considered for more effective therapy.Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform.Over 650 proteins were detected and relatively quantified.

View Article: PubMed Central - PubMed

Affiliation: Stoller Biomarker Discovery Centre, Manchester Academic Health Science Centre, The University of Manchester, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.

ABSTRACT
Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.

No MeSH data available.


Related in: MedlinePlus

Combination of LRG1 and CRP as a multiplexed biomarker can discriminate between survival groups and may add value to the use of gross tumour volume as a predictor of survival. Scatter plots of survival less than 14 mo (circle) and more than 18 mo (squares) compared to (a) combined levels of CRP and LRG1 in the plasma of SqCC patients during radiotherapy and (b) gross tumour volume (cm3). Significance was tested using a 2-tailed unpaired Mann Whitney test.
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f0020: Combination of LRG1 and CRP as a multiplexed biomarker can discriminate between survival groups and may add value to the use of gross tumour volume as a predictor of survival. Scatter plots of survival less than 14 mo (circle) and more than 18 mo (squares) compared to (a) combined levels of CRP and LRG1 in the plasma of SqCC patients during radiotherapy and (b) gross tumour volume (cm3). Significance was tested using a 2-tailed unpaired Mann Whitney test.

Mentions: Since both CRP and LRG1 were found to be significant predictive markers of survival for squamous cell carcinoma patients undergoing radiotherapy, we determined whether combining the levels of the two proteins linearly could be of value. This increased the significance of the difference between the good and poor prognosis groups (p = 0.0043). Using a cut-off value of a combined level of 140 mg/L all patients could be stratified into the correct group of < 14 mo and > 18 mo (Fig. 4a). LRG1 or CRP used in isolation does not result in this complete stratification. Gross tumour value was also available for ten of the patients (5 < 14 mo and 5 > 18 mo) analysed, since this has previously been shown to be a predictive marker of survival for radiotherapy of lung cancer patients this was also tested. This showed a significant difference (p = 0.0317) between the two survival groups but could not fully discriminate all the patients (Fig. 4b).


Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value.

Walker MJ, Zhou C, Backen A, Pernemalm M, Williamson AJ, Priest LJ, Koh P, Faivre-Finn C, Blackhall FH, Dive C, Whetton AD - EBioMedicine (2015)

Combination of LRG1 and CRP as a multiplexed biomarker can discriminate between survival groups and may add value to the use of gross tumour volume as a predictor of survival. Scatter plots of survival less than 14 mo (circle) and more than 18 mo (squares) compared to (a) combined levels of CRP and LRG1 in the plasma of SqCC patients during radiotherapy and (b) gross tumour volume (cm3). Significance was tested using a 2-tailed unpaired Mann Whitney test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563120&req=5

f0020: Combination of LRG1 and CRP as a multiplexed biomarker can discriminate between survival groups and may add value to the use of gross tumour volume as a predictor of survival. Scatter plots of survival less than 14 mo (circle) and more than 18 mo (squares) compared to (a) combined levels of CRP and LRG1 in the plasma of SqCC patients during radiotherapy and (b) gross tumour volume (cm3). Significance was tested using a 2-tailed unpaired Mann Whitney test.
Mentions: Since both CRP and LRG1 were found to be significant predictive markers of survival for squamous cell carcinoma patients undergoing radiotherapy, we determined whether combining the levels of the two proteins linearly could be of value. This increased the significance of the difference between the good and poor prognosis groups (p = 0.0043). Using a cut-off value of a combined level of 140 mg/L all patients could be stratified into the correct group of < 14 mo and > 18 mo (Fig. 4a). LRG1 or CRP used in isolation does not result in this complete stratification. Gross tumour value was also available for ten of the patients (5 < 14 mo and 5 > 18 mo) analysed, since this has previously been shown to be a predictive marker of survival for radiotherapy of lung cancer patients this was also tested. This showed a significant difference (p = 0.0317) between the two survival groups but could not fully discriminate all the patients (Fig. 4b).

Bottom Line: Identification of such markers would allow treatment options to be considered for more effective therapy.Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform.Over 650 proteins were detected and relatively quantified.

View Article: PubMed Central - PubMed

Affiliation: Stoller Biomarker Discovery Centre, Manchester Academic Health Science Centre, The University of Manchester, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.

ABSTRACT
Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.

No MeSH data available.


Related in: MedlinePlus