Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer
Autori
Marolt, NikaWalakira, Andrew
Režen, Tadeja
Rozman, Damjana
Lanišnik Rižner, Tea
Ostala autorstva
Morić, IvanaĐorđević, Valentina
Konferencijski prilog (Objavljena verzija)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
High-grade serous ovarian cancer (HGSOC) is the most aggressive and chemoresistant form of
epithelial ovarian cancer (OC) and is responsible for ~80% of OC-related deaths. OC is associated with
disturbed estrogen action. In postmenopausal patients, estrogens are formed locally from steroid
precursors. Enzymes of the AKR1C subfamily are associated with resistance to chemotherapeutic
agents and are involved in the biosynthesis and metabolism of steroid hormones, thus may
contribute to the growth of hormone-dependent tumors. To date, the interplay of estrogen
synthesis and aldo-keto reductase activity in HGSOC chemoresistance remains unclear.
The aim of this study was to investigate the differences in targeted transcriptomics of HGSOC
cell lines with different sensitivity to carboplatin: OVSAHO, OVCAR-3, Kuramochi, OVCAR-4, Caov-
3, and COV362, and to evaluate the differences in correlation patterns between targeted gene
expression profiles in platinum-sensitive and -resistant p...atients using publicly available data
(PAD) (cBioPortal).
We first determined the expression of genes involved in estrogen biosynthesis/metabolism (STS,
SULT1E1, HSD17B1, HSD17B2, HSD17B14, PAPSS1, PAPSS2), steroid transport (SLCO1A2, SLCO1B3,
SLCO2B1, SLCO4A1, SLCO4C1, ABCC1, ABCC4, ABCC11, ABCG2, SLC51A, SLC51B), estrogen action
(ESR1, ESR2, GPER) and oxidative metabolism (CYP1A1, CYP1A2, CYP1B1, SULT1A1, SULT2B1,
SULT1E1, UGTB7, COMT, NOQ1, NOQ2, GSTP1), NFE2L2 and AKR1C1-3 by qPCR. Next, by using PAD
we conducted a correlation analysis using the Pearson correlation coefficient for gene expression
data of targeted genes in OC patients. The patients were classified into two groups based on their
response to platinum treatment: sensitive and resistant. The correlation matrix was computed
independently for each group.
Expression analysis revealed that the estrogen receptor ESR2, the efflux transporter ABCG2
and aldo-keto reductase AKR1C1 were highly expressed in the most resistant cell lines COV362
and Caov-3. The mRNA levels of estrogen biosynthesis and oxidative metabolism genes STS,
HSD17B14, NOQ1, and GSTP1 increased with carboplatin resistance in the HGSOC cell lines. These
results indicate the potential of ESR2, STS, HSD17B14, NOQ1, GSTP1, and ABCG2 as predictive
markers for HGSOC chemoresistance. Furthermore, analysis of PAD revealed different correlation
profiles between genes in sensitive and resistant patients. In chemoresistant were found a
moderately to strong positive correlations (p<0.001) between gene pairs including AKR1C1–
AKR1C3, AKR1C1 – NFE2L2, AKR1C1 – SULT1E1, NOQ1 – HSD17B14, COMT – SULT1A1, ABCG2 –
SLC515. In chemosensitive patients was found a strong positive correlation (p<0.001) between
gene pair CYP1B1 – SULT1E1. The correlation differences between sensitive and resistant OC
patients suggest possible gene regulatory networks or molecular interactions contributing to
the heterogeneity of response to platinum in OC. Further studies are ongoing to elucidate the
mechanism of the interplay between local estrogen metabolism and aldo-keto reductase activity
in HGSOC chemoresistance
Ključne reči:
estrogen / ovarian cancerIzvor:
4th Belgrade Bioinformatics Conference, 2023, 4, 66-66Izdavač:
- Belgrade : Institute of molecular genetics and genetic engineering
Napomena:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Kolekcije
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Marolt, Nika AU - Walakira, Andrew AU - Režen, Tadeja AU - Rozman, Damjana AU - Lanišnik Rižner, Tea PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2006 AB - High-grade serous ovarian cancer (HGSOC) is the most aggressive and chemoresistant form of epithelial ovarian cancer (OC) and is responsible for ~80% of OC-related deaths. OC is associated with disturbed estrogen action. In postmenopausal patients, estrogens are formed locally from steroid precursors. Enzymes of the AKR1C subfamily are associated with resistance to chemotherapeutic agents and are involved in the biosynthesis and metabolism of steroid hormones, thus may contribute to the growth of hormone-dependent tumors. To date, the interplay of estrogen synthesis and aldo-keto reductase activity in HGSOC chemoresistance remains unclear. The aim of this study was to investigate the differences in targeted transcriptomics of HGSOC cell lines with different sensitivity to carboplatin: OVSAHO, OVCAR-3, Kuramochi, OVCAR-4, Caov- 3, and COV362, and to evaluate the differences in correlation patterns between targeted gene expression profiles in platinum-sensitive and -resistant patients using publicly available data (PAD) (cBioPortal). We first determined the expression of genes involved in estrogen biosynthesis/metabolism (STS, SULT1E1, HSD17B1, HSD17B2, HSD17B14, PAPSS1, PAPSS2), steroid transport (SLCO1A2, SLCO1B3, SLCO2B1, SLCO4A1, SLCO4C1, ABCC1, ABCC4, ABCC11, ABCG2, SLC51A, SLC51B), estrogen action (ESR1, ESR2, GPER) and oxidative metabolism (CYP1A1, CYP1A2, CYP1B1, SULT1A1, SULT2B1, SULT1E1, UGTB7, COMT, NOQ1, NOQ2, GSTP1), NFE2L2 and AKR1C1-3 by qPCR. Next, by using PAD we conducted a correlation analysis using the Pearson correlation coefficient for gene expression data of targeted genes in OC patients. The patients were classified into two groups based on their response to platinum treatment: sensitive and resistant. The correlation matrix was computed independently for each group. Expression analysis revealed that the estrogen receptor ESR2, the efflux transporter ABCG2 and aldo-keto reductase AKR1C1 were highly expressed in the most resistant cell lines COV362 and Caov-3. The mRNA levels of estrogen biosynthesis and oxidative metabolism genes STS, HSD17B14, NOQ1, and GSTP1 increased with carboplatin resistance in the HGSOC cell lines. These results indicate the potential of ESR2, STS, HSD17B14, NOQ1, GSTP1, and ABCG2 as predictive markers for HGSOC chemoresistance. Furthermore, analysis of PAD revealed different correlation profiles between genes in sensitive and resistant patients. In chemoresistant were found a moderately to strong positive correlations (p<0.001) between gene pairs including AKR1C1– AKR1C3, AKR1C1 – NFE2L2, AKR1C1 – SULT1E1, NOQ1 – HSD17B14, COMT – SULT1A1, ABCG2 – SLC515. In chemosensitive patients was found a strong positive correlation (p<0.001) between gene pair CYP1B1 – SULT1E1. The correlation differences between sensitive and resistant OC patients suggest possible gene regulatory networks or molecular interactions contributing to the heterogeneity of response to platinum in OC. Further studies are ongoing to elucidate the mechanism of the interplay between local estrogen metabolism and aldo-keto reductase activity in HGSOC chemoresistance PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer EP - 66 SP - 66 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_2006 ER -
@conference{ author = "Marolt, Nika and Walakira, Andrew and Režen, Tadeja and Rozman, Damjana and Lanišnik Rižner, Tea", year = "2023", abstract = "High-grade serous ovarian cancer (HGSOC) is the most aggressive and chemoresistant form of epithelial ovarian cancer (OC) and is responsible for ~80% of OC-related deaths. OC is associated with disturbed estrogen action. In postmenopausal patients, estrogens are formed locally from steroid precursors. Enzymes of the AKR1C subfamily are associated with resistance to chemotherapeutic agents and are involved in the biosynthesis and metabolism of steroid hormones, thus may contribute to the growth of hormone-dependent tumors. To date, the interplay of estrogen synthesis and aldo-keto reductase activity in HGSOC chemoresistance remains unclear. The aim of this study was to investigate the differences in targeted transcriptomics of HGSOC cell lines with different sensitivity to carboplatin: OVSAHO, OVCAR-3, Kuramochi, OVCAR-4, Caov- 3, and COV362, and to evaluate the differences in correlation patterns between targeted gene expression profiles in platinum-sensitive and -resistant patients using publicly available data (PAD) (cBioPortal). We first determined the expression of genes involved in estrogen biosynthesis/metabolism (STS, SULT1E1, HSD17B1, HSD17B2, HSD17B14, PAPSS1, PAPSS2), steroid transport (SLCO1A2, SLCO1B3, SLCO2B1, SLCO4A1, SLCO4C1, ABCC1, ABCC4, ABCC11, ABCG2, SLC51A, SLC51B), estrogen action (ESR1, ESR2, GPER) and oxidative metabolism (CYP1A1, CYP1A2, CYP1B1, SULT1A1, SULT2B1, SULT1E1, UGTB7, COMT, NOQ1, NOQ2, GSTP1), NFE2L2 and AKR1C1-3 by qPCR. Next, by using PAD we conducted a correlation analysis using the Pearson correlation coefficient for gene expression data of targeted genes in OC patients. The patients were classified into two groups based on their response to platinum treatment: sensitive and resistant. The correlation matrix was computed independently for each group. Expression analysis revealed that the estrogen receptor ESR2, the efflux transporter ABCG2 and aldo-keto reductase AKR1C1 were highly expressed in the most resistant cell lines COV362 and Caov-3. The mRNA levels of estrogen biosynthesis and oxidative metabolism genes STS, HSD17B14, NOQ1, and GSTP1 increased with carboplatin resistance in the HGSOC cell lines. These results indicate the potential of ESR2, STS, HSD17B14, NOQ1, GSTP1, and ABCG2 as predictive markers for HGSOC chemoresistance. Furthermore, analysis of PAD revealed different correlation profiles between genes in sensitive and resistant patients. In chemoresistant were found a moderately to strong positive correlations (p<0.001) between gene pairs including AKR1C1– AKR1C3, AKR1C1 – NFE2L2, AKR1C1 – SULT1E1, NOQ1 – HSD17B14, COMT – SULT1A1, ABCG2 – SLC515. In chemosensitive patients was found a strong positive correlation (p<0.001) between gene pair CYP1B1 – SULT1E1. The correlation differences between sensitive and resistant OC patients suggest possible gene regulatory networks or molecular interactions contributing to the heterogeneity of response to platinum in OC. Further studies are ongoing to elucidate the mechanism of the interplay between local estrogen metabolism and aldo-keto reductase activity in HGSOC chemoresistance", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer", pages = "66-66", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_2006" }
Marolt, N., Walakira, A., Režen, T., Rozman, D.,& Lanišnik Rižner, T.. (2023). Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 66-66. https://hdl.handle.net/21.15107/rcub_imagine_2006
Marolt N, Walakira A, Režen T, Rozman D, Lanišnik Rižner T. Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer. in 4th Belgrade Bioinformatics Conference. 2023;4:66-66. https://hdl.handle.net/21.15107/rcub_imagine_2006 .
Marolt, Nika, Walakira, Andrew, Režen, Tadeja, Rozman, Damjana, Lanišnik Rižner, Tea, "Possible role of estrogen metabolism and aldo-keto reductase activity in chemoresistance of ovarian cancer" in 4th Belgrade Bioinformatics Conference, 4 (2023):66-66, https://hdl.handle.net/21.15107/rcub_imagine_2006 .