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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

The acute phase response is not generally up regulated in patients with < 14 mo survival. The acute phase response pathway adapted from ingenuity software, highlighting the position of IL6 (blue circle) and the proteins identified in this study (purple) with up regulated proteins (red).
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f0025: The acute phase response is not generally up regulated in patients with < 14 mo survival. The acute phase response pathway adapted from ingenuity software, highlighting the position of IL6 (blue circle) and the proteins identified in this study (purple) with up regulated proteins (red).

Mentions: To understand the biological process that may cause or be related to the changes observed in < 14 mo survival patients in response to radiotherapy we analysed the contexts in which CRP and LBP may change. Ingenuity analysis showed that the acute phase response pathway is enriched in the identified dataset with 29 proteins from the pathway seen (see Fig. 5), however only CRP showed the expected difference between outcomes consistent with this pathway taking into account p value alone (Table 2). This indicates that the increased levels of CRP in < 14 mo survival patients may not be due to a general increase in the acute phase response. In the acute phase response CRP and LBP are both potentially regulated by changes in the levels of Interleukin 6 (IL-6) (Ganapathi et al., 1990, Castell et al., 1989, Castell et al., 1988, Moshage et al., 1988, Dentener et al., 2000, Grube et al., 1994). Furthermore a previous study identified IL-6 as a possible predictive marker for survival radiotherapy (Dehing-Oberije et al., 2011). The level of IL-6 was available for eight of the squamous cell carcinoma patients during treatment and so its correlation with CRP, LRG1 and LBP was investigated during radiotherapy. The correlation coefficient with IL-6 was significant for CRP with 0.86 (p value 0.006) and LRG1 0.751 (p value 0.032) but not for LBP with 0.52 (p value 0.191).


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)

The acute phase response is not generally up regulated in patients with < 14 mo survival. The acute phase response pathway adapted from ingenuity software, highlighting the position of IL6 (blue circle) and the proteins identified in this study (purple) with up regulated proteins (red).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0025: The acute phase response is not generally up regulated in patients with < 14 mo survival. The acute phase response pathway adapted from ingenuity software, highlighting the position of IL6 (blue circle) and the proteins identified in this study (purple) with up regulated proteins (red).
Mentions: To understand the biological process that may cause or be related to the changes observed in < 14 mo survival patients in response to radiotherapy we analysed the contexts in which CRP and LBP may change. Ingenuity analysis showed that the acute phase response pathway is enriched in the identified dataset with 29 proteins from the pathway seen (see Fig. 5), however only CRP showed the expected difference between outcomes consistent with this pathway taking into account p value alone (Table 2). This indicates that the increased levels of CRP in < 14 mo survival patients may not be due to a general increase in the acute phase response. In the acute phase response CRP and LBP are both potentially regulated by changes in the levels of Interleukin 6 (IL-6) (Ganapathi et al., 1990, Castell et al., 1989, Castell et al., 1988, Moshage et al., 1988, Dentener et al., 2000, Grube et al., 1994). Furthermore a previous study identified IL-6 as a possible predictive marker for survival radiotherapy (Dehing-Oberije et al., 2011). The level of IL-6 was available for eight of the squamous cell carcinoma patients during treatment and so its correlation with CRP, LRG1 and LBP was investigated during radiotherapy. The correlation coefficient with IL-6 was significant for CRP with 0.86 (p value 0.006) and LRG1 0.751 (p value 0.032) but not for LBP with 0.52 (p value 0.191).

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