Maria Dung Cao

Norwegian version of this page Department of Nursing, Health and laboratory science

Press photo

Norwegian version of this page Position

Associate Professor

Contact

+4769608741

maria.d.cao@hiof.no

Study place

Fredrikstad

Office nr.

S-420

Academic interests

Medical biochemistry, biology and genetics
Molecular diagnostics, bioinformatics and cancer research

Courses taught

Medisinsk biokjemi (IRBIO20320)
Celle- og molekylærbiologi (IRBIO10520)
Immunologi, hematologi og transfusjonsmedisin (IRBIO20120)
Molekylær diagnostikk og bioinformatikk (IRBIO30220)

Education

Doctor of Philosophy in Molecular Medicine (2008 – 2012)

Norwegian University of Science and Technology (NTNU), Norway

Doctoral thesis “MR metabolic characterization of locally advanced breast cancer – treatment effects and prognosis”

Master's Degree in Molecular Medicine (2006-2008)

Norwegian University of Science and Technology (NTNU), Norway

Master’s thesis ”Effect of dietary tetradecylthioacetic acid on SW620 colon cancer xenografts – a gene expression study”

Bachelor's Degree in Biomedical Science (2001 – 2004)

Østfold University College (HiØ), Norway

Bachelor’s thesis ”Screening a presumed healthy population for the T>C nucleotide substitution in the xanthine oxidoreductase gene using the dHPLC method”

Research stays abroad

Huddersfield University, UK (2004)
Johns Hopkins University School of Medicine, USA (2010 and 2013)

Tags: Biomedical laboratory scientist, medical biochemistry, biology, genetics, cancer research

Cao, Maria Dung; Jacobsen, Bente Marie Berntsen; Lie-Jensen, Anette Christensen; Ruud, Herman Sundet & Syversen, Linda (2026). Evaluering av blodprøvetaking ved studentdrevet poliklinikk. Bioingeniøren. ISSN 0801-6828. Full text in Research Archive Show summary
Originalartikkel om studentpoliklinikk som styrker ferdighetstrening i blodprøvetaking og gir mengdetrening i et trygt læringsmiljø.
Pedersen, Christine Aaserød; Cao, Maria Dung; Fleischer, Thomas; Rye, Morten Beck; Knappskog, Stian & Eikesdal, Hans Petter [Show all 12 contributors for this article] (2022). DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival. Breast Cancer Research. ISSN 1465-5411. 24:43(1), p. 1–14. doi: 10.1186/s13058-022-01537-9. Full text in Research Archive Show summary
Background Locally advanced breast cancer is a heterogeneous disease with respect to response to neoadjuvant chemotherapy (NACT) and survival. It is currently not possible to accurately predict who will benefit from the specific types of NACT. DNA methylation is an epigenetic mechanism known to play an important role in regulating gene expression and may serve as a biomarker for treatment response and survival. We investigated the potential role of DNA methylation as a prognostic marker for long-term survival (> 5 years) after NACT in breast cancer. Methods DNA methylation profiles of pre-treatment (n = 55) and post-treatment (n = 75) biopsies from 83 women with locally advanced breast cancer were investigated using the Illumina HumanMethylation450 BeadChip. The patients received neoadjuvant treatment with epirubicin and/or paclitaxel. Linear mixed models were used to associate DNA methylation to treatment response and survival based on clinical response to NACT (partial response or stable disease) and 5-year survival, respectively. LASSO regression was performed to identify a risk score based on the statistically significant methylation sites and Kaplan–Meier curve analysis was used to estimate survival probabilities using ten years of survival follow-up data. The risk score developed in our discovery cohort was validated in an independent validation cohort consisting of paired pre-treatment and post-treatment biopsies from 85 women with locally advanced breast cancer. Patients included in the validation cohort were treated with either doxorubicin or 5-FU and mitomycin NACT. Results DNA methylation patterns changed from before to after NACT in 5-year survivors, while no significant changes were observed in non-survivors or related to treatment response. DNA methylation changes included an overall loss of methylation at CpG islands and gain of methylation in non-CpG islands, and these changes affected genes linked to transcription factor activity, cell adhesion and immune functions. A risk score was developed based on four methylation sites which successfully predicted long-term survival in our cohort (p = 0.0034) and in an independent validation cohort (p = 0.049). Conclusion Our results demonstrate that DNA methylation patterns in breast tumors change in response to NACT. These changes in DNA methylation show potential as prognostic biomarkers for breast cancer survival.
Madssen, Torfinn Støve; Cao, Maria Dung; Pladsen, Arne Valebjørg; Ottestad, Lars; Sahlberg, Kristine Kleivi & Bathen, Tone Frost [Show all 7 contributors for this article] (2019). Historical Biobanks in Breast Cancer Metabolomics — Challenges and Opportunities. Metabolites. 9(11). doi: 10.3390/metabo9110278. Full text in Research Archive Show summary
Background: Metabolomic characterization of tumours can potentially improve prediction of cancer prognosis and treatment response. Here, we describe efforts to validate previous metabolomic findings using a historical cohort of breast cancer patients and discuss challenges with using older biobanks collected with non-standardized sampling procedures. Methods: In total, 100 primary breast cancer samples were analysed by high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and subsequently examined by histology. Metabolomic profiles were related to the presence of cancer tissue, hormone receptor status, T-stage, N-stage, and survival. RNA integrity number (RIN) and metabolomic profiles were compared with an ongoing breast cancer biobank. Results: The 100 samples had a median RIN of 4.3, while the ongoing biobank had a significantly higher median RIN of 6.3 (p = 5.86 × 10−7). A low RIN was associated with changes in choline-containing metabolites and creatine, and the samples in the older biobank showed metabolic differences previously associated with tissue degradation. The association between metabolomic profile and oestrogen receptor status was in accordance with previous findings, however, with a lower classification accuracy. Conclusions: Our findings highlight the importance of standardized biobanking procedures in breast cancer metabolomics studies.
Cao, Maria Dung; Cheng, Menglin; Rizwan, Asif; Jiang, Lu; Krishnamachary, Balaji & Bhujwalla, Zaver M. [Show all 8 contributors for this article] (2016). Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation, migration, and invasion. NMR in Biomedicine. ISSN 0952-3480. 29(8), p. 1098–1107. doi: 10.1002/nbm.3573. Full text in Research Archive
Giskeødegård, Guro F.; Cao, Maria Dung & Bathen, Tone Frost (2015). High-Resolution Magic-Angle-Spinning NMR Spectroscopy of Intact Tissue. Methods in molecular biology. ISSN 1064-3745. 1277, p. 37–50. doi: 10.1007/978-1-4939-2377-9_4. Full text in Research Archive
Wijnen, Jannie p; Jiang, L; Greenwood, TR; Cheng, M; Dopkens, M & Cao, Maria Dung [Show all 10 contributors for this article] (2014). Silencing of the glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by 31P MRS. NMR in Biomedicine. ISSN 0952-3480. 27(6), p. 692–699. doi: 10.1002/nbm.3106. Full text in Research Archive
Cao, Maria Dung; Lamichhane, Santosh; Lundgren, Steinar; Bofin, Anna M.; Fjøsne, Hans Erikssønn & Giskeødegård, Guro F. [Show all 7 contributors for this article] (2014). Metabolic characterization of triple negative breast cancer. BMC Cancer. 14(941), p. 941–941. doi: 10.1186/1471-2407-14-941. Full text in Research Archive Show summary
Background The aims of this study were to characterize the metabolite profiles of triple negative breast cancer (TNBC) and to investigate the metabolite profiles associated with human epidermal growth factor receptor-2/neu (HER-2) overexpression using ex vivo high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolic alterations caused by the different estrogen receptor (ER), progesterone receptor (PgR) and HER-2 receptor statuses were also examined. To investigate the metabolic differences between two distinct receptor groups, TNBC tumors were compared to tumors with ERpos/PgRpos/HER-2pos status which for the sake of simplicity is called triple positive breast cancer (TPBC). Methods The study included 75 breast cancer patients without known distant metastases. HR MAS MRS was performed for identification and quantification of the metabolite content in the tumors. Multivariate partial least squares discriminant analysis (PLS-DA) modeling and relative metabolite quantification were used to analyze the MR data. Results Choline levels were found to be higher in TNBC compared to TPBC tumors, possibly related to cell proliferation and oncogenic signaling. In addition, TNBC tumors contain a lower level of Glutamine and a higher level of Glutamate compared to TPBC tumors, which indicate an increase in glutaminolysis metabolism. The development of glutamine dependent cell growth or “Glutamine addiction” has been suggested as a new therapeutic target in cancer. Our results show that the metabolite profiles associated with HER-2 overexpression may affect the metabolic characterization of TNBC. High Glycine levels were found in HER-2pos tumors, which support Glycine as potential marker for tumor aggressiveness. Conclusions Metabolic alterations caused by the individual and combined receptors involved in breast cancer progression can provide a better understanding of the biochemical changes underlying the different breast cancer subtypes. Studies are needed to validate the potential of metabolic markers as targets for personalized treatment of breast cancer subtypes.
Gadiya, Mayur M.; Mori, N; Cao, Maria Dung; Mironchik, Y; Kakkad, S & Gribbestad, Ingrid S [Show all 9 contributors for this article] (2014). Phospholipase D1 and choline kinase-α are interactive targets in breast cancer. Cancer Biology & Therapy. ISSN 1538-4047. 15(5), p. 593–601. doi: 10.4161/cbt.28165. Full text in Research Archive
Cao, Maria Dung; Döpkens, Mailin; Krishnamachary, Balaji; Vesuna, Farhad; Gadiya, Mayur M. & Lønning, Per Eystein [Show all 9 contributors for this article] (2012). Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer. NMR in Biomedicine. ISSN 0952-3480. 25(9), p. 1033–1042. doi: 10.1002/nbm.2766. Full text in Research Archive
Cao, Maria Dung; Giskeødegård, Guro F.; Bathen, Tone Frost; Sitter, Beathe; Bofin, Anna M. & Lønning, Per Eystein [Show all 8 contributors for this article] (2012). Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy. BMC Cancer. 12. doi: 10.1186/1471-2407-12-39. Full text in Research Archive Show summary
Background Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC), relating these changes to clinical treatment response and long-term survival. Methods Patients (n = 89) participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy. Biopsies were excised pre- and post-treatment, and analyzed by high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The metabolite profiles were examined by paired and unpaired multivariate methods and findings of important metabolites were confirmed by spectral integration of the metabolite peaks. Results All patients had a significant metabolic response to NAC, and pre- and post-treatment spectra could be discriminated with 87.9%/68.9% classification accuracy by paired/unpaired partial least squares discriminant analysis (PLS-DA) (p < 0.001). Similar metabolic responses were observed for the two chemotherapeutic agents. The metabolic responses were related to patient outcome. Non-survivors (< 5 years) had increased tumor levels of lactate (p = 0.004) after treatment, while survivors (≥ 5 years) experienced a decrease in the levels of glycine (p = 0.047) and choline-containing compounds (p ≤ 0.013) and an increase in glucose (p = 0.002) levels. The metabolic responses were not related to clinical treatment response. Conclusions The differences in tumor metabolic response to NAC were associated with breast cancer survival, but not to clinical response. Monitoring metabolic responses to NAC by HR MAS MRS may provide information about tumor biology related to individual prognosis.
Cao, Maria Dung; Sitter, Beathe; Bathen, Tone Frost; Bofin, Anna M.; Lønning, Per Eystein & Lundgren, Steinar [Show all 7 contributors for this article] (2012). Predicting long-term survival and treatment response in breast cancer patients receiving neoadjuvant chemotherapy by MR metabolic profiling. NMR in Biomedicine. ISSN 0952-3480. 25(2), p. 369–378. doi: 10.1002/nbm.1762. Full text in Research Archive

View all works in NVA

Jacobsen, Bente Marie Berntsen; Cao, Maria Dung; Lie-Jensen, Anette Christensen; Karlsen, Anne Palacios; Lystad, Rita & Ruud, Herman Sundet [Show all 7 contributors for this article] (2025). Erfaring med etablering av studentdrevet poliklinikk Et samarbeid mellom Høgskolen i Østfold og Sykehuset Østfold. Bioingeniøren. ISSN 0801-6828. doi: https:/www.bioingenioren.no/fag/erfaring-med-etablering-av-studentdrevet-poliklinikk-et-samarbeid-mellom-hogskolen-i-ostfold-og-sykehuset-ostfold/142127. Full text in Research Archive Show summary
Studenter ved bioingeniørutdanningen ved Høgskolen i Østfold får utvidet og verdifull ferdighetstrening i blodprøvetaking gjennom etableringen av en studentdrevet poliklinikk for blodprøvetaking i samarbeid med Sykehuset Østfold.
Cao, Maria Dung & Jacobsen, Bente Marie Berntsen (2024). Mestringstillit i blodprøvetaking. Full text in Research Archive
Cao, Maria Dung & Jacobsen, Bente Marie Berntsen (2024). Ferdighetstrening i blodprøvetaking ved studentdrevet poliklinikk. Full text in Research Archive
Volchenkov, Roman; Cao, Maria Dung; Elgstøen, Katja B. Prestø; Goll, Guro Løvik; Eikvar, Kari & Bjørneboe, Olav [Show all 10 contributors for this article] (2017). Metabolic profiling of synovial tissue shows altered glucose and choline metabolism in rheumatoid arthritis samples. Scandinavian Journal of Rheumatology. ISSN 0300-9742. 46(2), p. 160–161. doi: 10.3109/03009742.2016.1164242. Full text in Research Archive
Cao, Maria Dung (2015). MR i kliniske og prekliniske studier av brystkreft. Full text in Research Archive
Cao, Maria Dung; Cheng, Menglin; Jiang, Lu; Greenwood, Tiffany; Krishnamachary, Balaji & Bhujwalla, Zaver M. [Show all 8 contributors for this article] (2014). Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decreases breast cancer cell proliferation and invasion. Full text in Research Archive
Cao, Maria Dung; Bathen, Tone Frost & Giskeødegård, Guro F. (2014). Methylation, metabolomics and response. Full text in Research Archive
Giskeødegård, Guro F.; Cao, Maria Dung; Lamichane, Santosh; Sitter, Beathe; Bofin, Anna M. & Lundgren, Steinar [Show all 8 contributors for this article] (2014). Metabolic characterization of triple negative breast cancer. Full text in Research Archive
Cao, Maria Dung (2014). The potential and challenges of HR MAS MRS in characterization of breast cancer. Full text in Research Archive
Sjøbakk, Torill Eidhammer; Hill, Deborah Katherine; Strypet, Hanne; Skjærvik, Linda; Evensmoen, Hallvard Røe & Selnæs, Kirsten Margrete [Show all 13 contributors for this article] (2014). MAGNETER OG MEDISIN Stand i samarbeid med Kreftforeingen v/Linda Skjærvik. Full text in Research Archive
Cao, Maria Dung; Giskeødegård, Guro F.; Santosh, Lamichhane; Sitter, Beathe; Lundgren, Steinar & Bofin, Anna M. [Show all 9 contributors for this article] (2013). Metabolic characterization of triple negative breast cancer. Full text in Research Archive
Cao, Maria Dung (2013). The potential role of Metabolomics in breast cancer diagnosis and prognosis. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Blackwell, Tiffany; Krishnamachary, Balaji; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2012). siRNA-mediated silencing of the glycerophosphocholine phosphodiesterase GDPD5 in breast cancer cells. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Blackwell, Tiffany; Krishnamachary, Balaji; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2012). Metabolic response to glycerophosphocholine phosphodiesterase GDPD5 silencing in human breast cancer cells. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Blackwell, Tiffany; Krishnamachary, Balaji; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2012). siRNA-mediated silencing of the glycerophosphocholine phosphodiesterase GDPD5 in breast cancer cells. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Blackwell, Tiffany; Krishnamachary, Balaji; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2012). Metabolic response to glycerophosphocholine phosphodiesterase GDPD5 silencing in human breast cancer cells. Full text in Research Archive
Cao, Maria Dung; Giskeødegård, Guro F.; Bathen, Tone Frost; Sitter, Beathe; Bofin, Anna M. & Lønning, Per Eystein [Show all 8 contributors for this article] (2012). Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Blackwell, Tiffany; Krishnamachary, Balaji; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2012). siRNA-mediated silencing of the glycerophosphocholine phosphodiesterase GDPD5 in breast cancer cells. Full text in Research Archive
Cao, Maria Dung & Giskeødegård, Guro F. (2012). Metabolomics of cancer tissue. Full text in Research Archive
Cao, Maria Dung (2012). Prediksjon av behandlingsrespons og overlevelse i pasienter med lokalavansert brystkreft. Best Practice Onkologi/Hematologi. Full text in Research Archive
Wijnen, Jannie p; Jiang, Lu; Blackwell, Tiffany; Cao, Maria Dung; Krishnamachary, Balaji & Klomp, Dennis WJ [Show all 7 contributors for this article] (2012). Magnetic Resonance Spectroscopy study on the effects of stably silencing the glycerophosphocholine phosphodiesterase GDPD5 in a breast cancer model in vivo. Full text in Research Archive
Moestue, Siver Andreas; Giskeødegård, Guro F.; Cao, Maria Dung; Bathen, Tone Frost & Gribbestad, Ingrid S (2012). Glycerophosphocholine (GPC) is a poorly understood biomarker in breast cancer. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 109(38), p. E2506–E2506. doi: 10.1073/pnas.1208226109. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Krishnamachary, Balaji; Doepkens, Mailin; Bhjuwalla, Zaver M. & Gribbestad, Ingrid S [Show all 7 contributors for this article] (2011). Effects of targeting the glycerophosphocholine phosphodiesterase GDPD5 in breast cancer models. Full text in Research Archive
Cao, Maria Dung; Jiang, Lu; Krishnamachary, Balaji; Doepkens, Mailin; Vesuna, Farhad & Lønning, Per Eystein [Show all 9 contributors for this article] (2011). GDPD5 expression correlates with choline metabolite profiles in human breast cancer. Full text in Research Archive
Cao, Maria Dung; Sitter, Beathe; Bathen, Tone Frost; Bofin, Anna M.; Lønning, Per Eystein & Lundgren, Steinar [Show all 7 contributors for this article] (2010). Predicting long-term survival for breast cancer patients by HR MAS metabolic profiling during neoadjuvant chemotherapy. Full text in Research Archive
Cao, Maria Dung; Sitter, Beathe; Bathen, Tone Frost; Bofin, Anna M.; Lønning, Per Eystein & Lundgren, Steinar [Show all 7 contributors for this article] (2010). Predicting long-term breast cancer survival in patients receiving neoadjuvant chemotherapy by MR metabolic profiling. Full text in Research Archive
Cao, Maria Dung; Ljiang, Lu; Doepkens, Mailin; Krishnamachary, Balaji; Blackwell, Tiffany & Bhujwalla, Zaver [Show all 8 contributors for this article] (2010). Silencing the glycerophosphocholine phosphodiesterase GDPD5 reduced breast tumor growth and modulated tumor choline phospholipid metabolism. Full text in Research Archive
Cao, Maria Dung (2010). Predicting treatment response and long-term breast cancer survival by HR MAS MRS metabolic profiling. Full text in Research Archive
Cao, Maria Dung; Sitter, Beathe; Bathen, Tone Frost; Lønning, Per E.; Lundgren, Steinar & Gribbestad, Ingrid S (2009). Choline metabolites as biomarkers for predicting response to neoadjuvant chemotherapy in local advanced breast cancer patients. Full text in Research Archive
Heldahl, Mariann Gjervik; Sitter, Beathe; Bathen, Tone Frost; Cao, Maria Dung; Lundgren, Steinar & Gribbestad, Ingrid S (2009). In vivo and ex vivo choline metabolite profiles as biomarkers for treatment response in locally advanced breast cancer. Full text in Research Archive
Bathen, Tone Frost; Cao, Maria Dung; Sitter, Beathe; Lønning, Per E.; Lundgren, Steinar & Gribbestad, Ingrid S (2009). MR metabolomics – a tool in detection of biomarkers for response to neoadjuvant chemotherapy in local advanced breast cancer? Full text in Research Archive
Huynh, Bao-Mai; Selnæs, Kirsten Margrete & Cao, Maria Dung (2014). Metabolic and Histopathological characterization of Prostate cancer. Norges teknisk-naturvitenskapelige universitet. Full text in Research Archive Show summary
Prostatakreft er en av hovedårsakene til kreftrelaterte dødsfall i verden. Fremskritt i kunnskap om denne sykdommen kan bidra til å forbedre utfallet av sykdommen hos pasienter. Biomarkører kan forbedre detekteringen kreften og bestemme stadiet kreften er kommet i. De kan også forbedre valget av behandlingen for spesifikke pasienter and predikere utfallet etter behandling. I dette studiet vil vi fokusere på metabolitter og histopatologisk farging som potesielle diagnostiske og prognostiske biomarkører for prostatakreft. Studiet inkluderte ett datasett ed 91 vevsprøver fra pasienter med prostatakreft som er hentet fra åpen prostatektomi. Alderen på pasientene varierte fra 46 til 72 år, med en midlere alder på 61. Alle pasienter hadde utviklet kreft fra prostata adenokarsinom og 41 av totale antall prøver ble testet postiv for maligne celler. Høyoppløselig magisk spinnende vinkel magnetisk resonans spektroskopi (high resolution magic angle spinning magnetic resonance spectroscopy) ble utført på vevsprøvene og et MR spektrum ble laget. Preprossesering ble gjennomført på spektrene fra spektroskopien for grunnlinjen og for forskyvede topper i spekteret. Spekteret som vi fikk etter preprossesering karakteriserer den metabolske profilen til prøvene i datasettet.Den metabolske profilen i det kjemiske spekteret ble analysert ut fra kliniske prognostiske parametere som prostata spesifikt antigen (PSA) og Gleason score via multivariat analyse. Den samme analysen ble gjennomført på resultater hentet fra histopatologiske farginger. Disse resultatene ble også brukt for å finne korrelasjoner mellom spesifikke metabolitter og mellom spesifikke proteiner og gener med tanke på kliniske prognostiske parametere. Funnene i dette studiet er høyere verdi av laktat ( p<0.001), choline ( p = 0.004) og glycerophosphocholine (GPC)( p = 0.001) i maligne prøver sammenlignet med ikke-maligne prøver, og lavere nivå av citrate ( p = 0.004) i de ikke-maligne prøvene. Funnene i dette studiet stemmer overens med tidligere studier som indikerer at metabolitter som laktat, GPC, choline og citrate kan brukes som diagnostiske biomarkører for prostatakreft. Det var ingen signifikante funn for metabolitter som kunne brukes som prognostiske biomarkører for prostatakreft.
Shojaei, Moghaddam Shiva; Cao, Maria Dung & Bathen, Tone (2013). Metabolic characterization of locally advanced breast cancer in response to NAC treatment based on HR MAS MRS. Norges teknisk-naturvitenskapelige universitet. Full text in Research Archive Show summary
Breast cancer is the most frequent cancer disease among women globally. Locally advanced breast cancer (LABC) consists of different groups of breast cancer patients with variable prognosis. Today’s treatment decision is mostly based on clinical assessment, histopathologocal evaluation, and hormone receptor and lymph node status. So far, these data are not sufficient for designing more effective personalized medicine or accurately predicting the prognosis of the disease. Metabolic characterization of tumors may assist clinicians to classify patients for more personalized treatment, and moreover, improving the prognosis. Magnetic resonance (MR) metabolomics assess the downstream product of gene and protein expression and provide predictive and prognostic information for several types of cancer. Proton high resolution magic angle spinning (1H HR MAS) MR spectroscopy is a nondestructive technique which was developed to improve the spectral resolution of MR spectra from intact tissue. The ERETIC method for accurate quantification was used to quantify metabolites. Recently, the metabolic changes have been suggested as a new emerging hallmark of cancer. Choline phospholipid metabolism is involved in cell signaling, lipid metabolism and participating in cell membrane structure. Several studies have suggested total choline containing metabolites (tCho) level as a biomarker for treatment evaluation of breast cancer. Moreover, it has become increasingly clear that high level of GPC is associated with poor prognosis in breast cancer. In this study, nonparametric tests on quantified metabolite data (acquired from 1H HR MAS MRS spectra) were performed to investigate potential biomarkers for prediction of prognosis in LABC patients receiving NAC treatment. The metabolite changes were also studied in order to find a pattern of metabolic changes in LABC patients pre- and post NAC treatment. In addition, the protocols of homogenization and RNA/DNA isolation from tissue samples were optimized. All patients had a metabolic response to NAC. This thesis demonstrates that MR metabolomics profile contains information that is associated with survival status response to treatment in LABC patients. Based on results by both paired and unpaired tests, survivors showed significant decrease in GPC level while non-survivors showed significant decrease in PG/GPC. Moreover, It is become increasingly clear that high level of GPC is associated with poor prognosis in breast cancer. It is also reported that the decreasing in GPC level in response to treatment is related to long-term survivors breast cancer. In normal mammary cell cultures, PC/GPC ratio increases during malignant transformation. The discrepancy between acquired result in this study and previous findings might be as a result of differences in microenvironment of mammary cell cultures and tumor biopsies. In the current study, responders showed significant increase in m-Ino while non-responders showed significant decrease in Cho and tCho. As reported by several studies, m-Ino has demonstrated anti-cancer functions in some of the cancers like breast and colon cancer. However, the molecular mechanisms underlying this anticancer action are not fully understood. In addition, the group with stable disease (non-responders) can obtain <50% decrease in tumor volume based on their definition. This might be the reason for having decrease in Cho and tCho levels in non-responders, which were not expected based on previous findings. After metabolic profiling of LABC patients, the gene and protein expression study on samples could be valuable to introduce over-expressed or down-regulated gene and proteins in patients. Optimization the RNA/DNA and protein isolation would be the first step on this research process. DNA samples concentrations showed to have high linear correlation with tumor cell content. DNA and RNA concentrations were also strongly correlated. The Mann Whitney test between different groups of patients based on their tumor cell content showed significant differences in DNA and RNA concentrations between groups with larger differences in their cell content. This would suggest that the most extracted DNA and RNA are from cancer cells not from normal cells present in the samples. In conclusion, the metabolite response to the NAC treatment in LABC patients may have the potential to assist the prediction of survival and help to identify new targets for LABC breast cancer treatment. Furthermore, high quality RNA and DNA samples would be valuable for further analyses in order to identify new targets for LABC treatment.
Cao, Maria Dung (2012). MR metabolic characterization of locally advanced breast cancer: – treatment effects and prognosis. Norges teknisk-naturvitenskapelige universitet. Full text in Research Archive Show summary
Breast cancer is the most frequent cancer disease among women globally. Locally advanced breast cancer (LABC) constitutes a heterogeneous group of patients with variable prognosis. Today’s treatment decision is predominately based on clinical assessment, histopathological evaluation, and hormone receptor and lymph node status. So far, these data are not sufficient for designing a proper personalized treatment or accurately predicting treatment response and survival. Molecular characterization of tumors may help stratifying patients for individualized treatment, thereby achieving better prognosis. Magnetic resonance (MR) metabolomics analyses assess the downstream products of gene and protein expressions, i.e. the metabolites, and have shown to provide both predictive and prognostic information for several types of cancers. Proton high resolution magic angle spinning (1H HR MAS) MR spectroscopy is a non-destructive and high-throughput technique that provides highly resolved MR spectra from biological tissue. Recently, altered cell metabolism is suggested as a new emerging hallmark of cancer. Choline phospholipid metabolism is involved in cell signaling, lipid metabolism, and the structural integrity of the cell membrane. Several MRS studies have suggested the total choline-containing metabolite (tCho) level as an in vivo biomarker for diagnosis and treatment evaluation of breast cancer. Reprogramming of energy metabolism and activation of tumor hypoxic response are commonly observed in cancers, and can be characterized by high lactate production. In this thesis, multivariate data analyses and metabolite quantification of 1H HR MAS MRS data were performed to investigate the potential of metabolomics for prediction of clinical response and long-term survival in LABC patients receiving neoadjuvant chemotherapy (NAC). In addition, the role of glycerophosphodiester phosphodiesterase (GDPD) in choline phospholipid metabolism of human breast cancer was investigated. All patients had a metabolic response to NAC and almost all patients had a reduction in tumor size. Our results show no clear differences in metabolic responses to NAC between patients with partial response and stable disease and no significant multivariate models for prediction of clinical response by MR metabolomics data. In general, all patients experienced a decrease in tCho levels. It is possible that a cohort including also patients with progressive disease would reveal clearer differences in the metabolite profiles between the clinical response groups. This thesis demonstrates that MR metabolomics contain prognostic information that is associated with survival status of LABC patients. Increase in lactate levels as a response to NAC was associated with low survival rates (< 5 years), while decreased glycine and choline phospholipid metabolites were associated with long-term survival (≥ 5 years). The observed metabolite profiles consisting of higher levels of lactate, glycine, and tCho post-treatment were predictive of low breast cancer survival rates. GDPD5 gene expression was correlated with choline phospholipid metabolite levels and with CHKA and PLD1 gene expressions suggesting GDPD5 to have a role in regulation of choline phospholipid metabolism in human breast cancer. However, more studies are needed to investigate the relationship between GDPD5 and tumor malignancy, and also estrogen receptor status, for use as target in breast cancer treatment. In conclusion, monitoring metabolic responses to NAC by MR metabolomics may have the potential to assist the prediction of survival and help identify new targets for therapeutic treatment of breast cancer.

View all works in NVA

Published June 12, 2018 4:17 PM - Last modified Oct. 20, 2021 3:12 PM