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Grupp Khalil Helou

Research summary

Novel prognostic and predictive biomarkers for treatment decisions in breast and ovarian cancer

Breast and ovarian cancers are among the most common malignancies among women worldwide. Approximately 20% of breast cancer patients will develop recurrence within 5 years after initial diagnosis. In addition, approximately 70% of newly diagnosed ovarian cancer patients are in stage III or IV, resulting in poor prognosis at the time of detection. There is, therefore, a need to improve patient risk assessment and to personalize therapy according to a combination of patient-specific clinicopathological features and tumor characteristics. To substantially increase the power to subclassify breast cancer and early-stage ovarian cancer patients, we will study the genetic makeup of tumor samples retrieved from the biobank at the Department of Oncology, Sahlgrenska University Hospital, in conjunction with clinical information from the National Quality Registry at the Regional Cancer Center West and the Cancer Registry at the National Board of Health and Welfare. In addition to conventional molecular and cellular biology techniques, statistical models will be used to identify novel biomarkers which can predict aggressive tumor behavior and detect invasive tumors at an early stage. In previous studies, we showed that a four-marker panel (AZGP1, PIP, S100A8, UBE2C) used in conjunction with established clinical variables significantly improved outcome prediction of breast cancer. Furthermore, these biomarkers might be targetable by proteasome and mitosis inhibitors.

We hypothesize that tumor biology, e.g. aberrant genetic and epigenetic changes, may guide the selection of therapeutic targets and refine assessment of prognosis, which in turn could have a decisive impact on the outcome of future cancer treatment. It is therefore important to determine the genetic and epigenetic events involved in cancer development.

The focus of this project is to (1) assess the tumorigenic and therapeutic potential of the four biomarkers in breast cancer cell lines and patient-derived xenografts, (2) identify novel genetic and epigenetic biomarkers associated with ovarian cancer-specific survival, and (3) examine whether the identified candidate biomarkers are breast/ovarian cancer-specific or general key cancer genes. Subsequently, these biomarkers may be useful as targets for early detection, drug development, patient stratification, and improved therapy.

Research Tools and Resources

We use several molecular biology technologies to study tumor biology, including array-CGH, gene expression microarrays, RNA-Seq, DNA methylation, FISH, immunohistochemistry, cell transfection, and qPCR. In addition to clinical breast and ovarian tumor samples, we also use tumor cell lines, primary cells and mouse xenografts as model systems.

Current Group Members

Khalil Helou, Associate Professor (Team Leader)
Per Karlsson, Professor, MD (breast cancer oncologist)
Zakaria Einbeigi, MD, PhD (breast cancer oncologist)
Anikó Kovács, Associate Professor, MD (Pathologist)
Toshima Parris, Postdoc (Molecular Biologist)
Szilárd Nemes, PhD (Statistician)
Hanna Engqvist, PhD Student
Jana Biermann, PhD Student
Elisabeth Werner Rönnerman, MD, PhD Student (Pathologist)
Luaay Aziz, MD, PhD Student (Surgeon, head and neck cancer)
May Semaan, (Technical Assistant)

Selected Publications

 

  1. Parris TZ, Danielsson A, Nemes S, Kovacs A, Delle U, Fallenius G, Mollerstrom E, Karlsson P, Helou K: Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma. Clin Cancer Res 2010, 16(15):3860-3874.
  2. Nemes S, Parris TZ, Danielsson A, Kannius-Janson M, Jonasson JM, Steineck G, Helou K: Segmented regression, a versatile tool to analyze mRNA levels in relation to DNA copy number aberrations. Genes, chromosomes & cancer 2012, 51(1):77-82.
  3. Parris T, Nik AM, Kotecha S, Langston C, Helou K, Platt C, Carlsson P: Inversion upstream of FOXF1 in a case of lethal alveolar capillary dysplasia with misalignment of pulmonary veins. American journal of medical genetics Part A 2013, 161(4):764-770.
  4. Shubbar E, Helou K, Kovacs A, Nemes S, Hajizadeh S, Enerback C, Einbeigi Z: High levels of gamma-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer. BMC cancer 2013, 13:47.
  5. Shubbar E, Kovacs A, Hajizadeh S, Parris TZ, Nemes S, Gunnarsdottir K, Einbeigi Z, Karlsson P, Helou K: Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome. BMC cancer 2013, 13:1.
  6. Nemes S, Danielsson A, Parris TZ, Miao Jonasson J, Bulow E, Karlsson P, Steineck G, Helou K: A diagnostic algorithm to identify paired tumors with clonal origin. Genes, chromosomes & cancer 2013.
  7. Parris TZ, Kovacs A, Aziz L, Hajizadeh S, Nemes S, Semaan M, Forssell-Aronsson E, Karlsson P, and Helou K: Additive effect of the AZGP1, PIP, S100A8, and UBE2C molecular biomarkers improves outcome prediction in breast carcinoma. Int J Cancer. 2014 Apr 1;134(7):1617-29. doi: 10.1002/ijc.28497.
  8. Nemes S, Parris TZ, Danielsson A, Einbeigi Z, Steineck G, Jonasson JM, and Helou K: Integrative genomics with mediation analysis in a survival context. Comput Math Methods Med. 2013;2013:413783. doi: 10.1155/2013/413783.
  9. Parris TZ., Kovacs A, Hajizadeh S, Nemes S, Semaan M, Levin M, Karlsson P, and Helou K: Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas. Oncogenesis. 2014 Mar 24;3:e95. doi: 10.1038/oncsis.2014.8.
  10. Parris TZ, Aziz L, Kovacs A, Hajizadeh S, Nemes S, Semaan M, Chen CY, Karlsson P, and Helou K: Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma. BMC Cancer. 2014 May 7;14:324. doi: 1186/1471-2407-14-324.
Sidansvarig: Ulrika Lantz Carlsson|Sidan uppdaterades: 2016-02-22
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