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Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma.

Salas S, Jiguet-Jiglaire C, Campion L, Bartoli C, Frassineti F, Deville JL, Maues De Paula A, Forest F, Jézéquel P, Gentet JC, Bouvier C - BMC Cancer (2014)

Bottom Line: Expression of selected relevant genes identified by SSH was validated by using QRT-PCR.ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort.Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Univ, CRO2, 13284 Marseille, France. sebastien.salas@ap-hm.fr.

ABSTRACT

Background: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as "poor responders" (PR) and "good responders" (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment.

Methods: Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort.

Results: ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy.

Conclusions: Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

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Related in: MedlinePlus

RTQ-PCR analysis of STAT3 and ERK1 genes. A: Quantification of STAT3 mRNA with 18S rRNA reference gene transcript confirmed higher STAT3 mRNA levels in poor responder (PR) samples compared with good responder (GR) samples (p = 0.019). B: Quantification of MAPK3 (ERK1) mRNA with 18S rRNA reference gene transcript confirmed higher MAPK3 (ERK1) mRNA levels in PR samples compared with GR samples (p = 0.046).
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Fig1: RTQ-PCR analysis of STAT3 and ERK1 genes. A: Quantification of STAT3 mRNA with 18S rRNA reference gene transcript confirmed higher STAT3 mRNA levels in poor responder (PR) samples compared with good responder (GR) samples (p = 0.019). B: Quantification of MAPK3 (ERK1) mRNA with 18S rRNA reference gene transcript confirmed higher MAPK3 (ERK1) mRNA levels in PR samples compared with GR samples (p = 0.046).

Mentions: Only STAT3 mRNA level and ERK1 mRNA level were significantly different between PR and GR. Quantification of STAT3 and ERK1 mRNA transcripts revealed higher mRNA levels in PR compared to GR samples (p = 0.019 and p = 0.046 respectively). The mean level of STAT3 mRNA was 0.820 [0.280-13.970] in PR versus 0.310 [0.230-2.370] in GR samples (Figure 1A) and the mean level of ERK1 was 0.270 [0.110-4.340] in PR versus 0.150 [0.088-0.710] in GR samples (Figure 1B).Figure 1


Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma.

Salas S, Jiguet-Jiglaire C, Campion L, Bartoli C, Frassineti F, Deville JL, Maues De Paula A, Forest F, Jézéquel P, Gentet JC, Bouvier C - BMC Cancer (2014)

RTQ-PCR analysis of STAT3 and ERK1 genes. A: Quantification of STAT3 mRNA with 18S rRNA reference gene transcript confirmed higher STAT3 mRNA levels in poor responder (PR) samples compared with good responder (GR) samples (p = 0.019). B: Quantification of MAPK3 (ERK1) mRNA with 18S rRNA reference gene transcript confirmed higher MAPK3 (ERK1) mRNA levels in PR samples compared with GR samples (p = 0.046).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150966&req=5

Fig1: RTQ-PCR analysis of STAT3 and ERK1 genes. A: Quantification of STAT3 mRNA with 18S rRNA reference gene transcript confirmed higher STAT3 mRNA levels in poor responder (PR) samples compared with good responder (GR) samples (p = 0.019). B: Quantification of MAPK3 (ERK1) mRNA with 18S rRNA reference gene transcript confirmed higher MAPK3 (ERK1) mRNA levels in PR samples compared with GR samples (p = 0.046).
Mentions: Only STAT3 mRNA level and ERK1 mRNA level were significantly different between PR and GR. Quantification of STAT3 and ERK1 mRNA transcripts revealed higher mRNA levels in PR compared to GR samples (p = 0.019 and p = 0.046 respectively). The mean level of STAT3 mRNA was 0.820 [0.280-13.970] in PR versus 0.310 [0.230-2.370] in GR samples (Figure 1A) and the mean level of ERK1 was 0.270 [0.110-4.340] in PR versus 0.150 [0.088-0.710] in GR samples (Figure 1B).Figure 1

Bottom Line: Expression of selected relevant genes identified by SSH was validated by using QRT-PCR.ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort.Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Univ, CRO2, 13284 Marseille, France. sebastien.salas@ap-hm.fr.

ABSTRACT

Background: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as "poor responders" (PR) and "good responders" (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment.

Methods: Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort.

Results: ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy.

Conclusions: Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

Show MeSH
Related in: MedlinePlus