Article Type
Changed
Fri, 01/18/2019 - 00:08
Display Headline
Biomarker Assays for Lung Cancer Fill Pipeline

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

Article PDF
Author and Disclosure Information

Publications
Topics
Author and Disclosure Information

Author and Disclosure Information

Article PDF
Article PDF

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

Publications
Publications
Topics
Article Type
Display Headline
Biomarker Assays for Lung Cancer Fill Pipeline
Display Headline
Biomarker Assays for Lung Cancer Fill Pipeline
Article Source

PURLs Copyright

Inside the Article

Article PDF Media