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Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer.

Nordgård O, Singh G, Solberg S, Jørgensen L, Halvorsen AR, Smaaland R, Brustugun OT, Helland Å - PLoS ONE (2013)

Bottom Line: LN and PB marker status were compared to clinicopathological patient data.A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. nood@sus.no

ABSTRACT

Introduction: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).

Methods: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.

Results: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).

Conclusions: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

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Related in: MedlinePlus

Relative marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN) and peripheral blood samples (nB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and not directly comparable.
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pone-0062153-g001: Relative marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN) and peripheral blood samples (nB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and not directly comparable.

Mentions: As a first validation of the 7 candidate markers, we measured their levels in 16 NSCLC tumor biopsies, 22 cancer-free LNs and 12 normal control PB samples by quantitative RT-PCR (Figure 1). Except for DSG3, the levels of all markers were much higher in the tumors compared with the control LNs and PB (P0.001). CEACAM5 and SFTPC mRNA were undetectable in normal blood samples. Interestingly, the level of SFTPA mRNA in the 6 control LNs from lungs was significantly higher than in the control LNs from the colon mesentery (P = 0.002). A similar tendency, although not statistically significant, was also observed for SFTPB and SFTPC, but not for the remaining candidate markers.


Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer.

Nordgård O, Singh G, Solberg S, Jørgensen L, Halvorsen AR, Smaaland R, Brustugun OT, Helland Å - PLoS ONE (2013)

Relative marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN) and peripheral blood samples (nB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and not directly comparable.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643953&req=5

pone-0062153-g001: Relative marker levels in non-small cell lung cancer (NSCLC) tumors (T), normal LNs (nN) and peripheral blood samples (nB).Median values are indicated by short horizontal lines, whereas samples with levels below the limit of detection (LOD) are indicated below the dashed horizontal line. The levels of the different markers are relative to a calibrator sample and not directly comparable.
Mentions: As a first validation of the 7 candidate markers, we measured their levels in 16 NSCLC tumor biopsies, 22 cancer-free LNs and 12 normal control PB samples by quantitative RT-PCR (Figure 1). Except for DSG3, the levels of all markers were much higher in the tumors compared with the control LNs and PB (P0.001). CEACAM5 and SFTPC mRNA were undetectable in normal blood samples. Interestingly, the level of SFTPA mRNA in the 6 control LNs from lungs was significantly higher than in the control LNs from the colon mesentery (P = 0.002). A similar tendency, although not statistically significant, was also observed for SFTPB and SFTPC, but not for the remaining candidate markers.

Bottom Line: LN and PB marker status were compared to clinicopathological patient data.A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. nood@sus.no

ABSTRACT

Introduction: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).

Methods: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.

Results: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).

Conclusions: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.

Show MeSH
Related in: MedlinePlus