Top

Published in:

01-04-2013 | Research Paper

Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors

Authors: George Pentheroudakis, Yael Spector, Dimitrios Krikelis, Vassiliki Kotoula, Eti Meiri, Vassiliki Malamou-Mitsi, George Fountzilas, Mats Sanden, Nicholas Pavlidis, Hila Benjamin, Ranit Aharonov

Published in: Clinical & Experimental Metastasis | Issue 4/2013

Abstract

No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17–92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive.

Available only for authorised users

Pavlidis N, Pentheroudakis G (2012) Cancer of unknown primary site. Lancet 379:1428–1435PubMedCrossRef

Pentheroudakis G, Briasoulis E, Pavlidis N (2007) Cancer of unknown primary site: missing primary or missing biology? Oncologist 12:418–425PubMedCrossRef

Monzon FA, Koen TJ (2010) Diagnosis of metastatic neoplasms: molecular approaches for identification of tissue of origin. Arch Pathol Lab Med 134:216–224PubMed

Pavlidis N, Petrakis D, Golfinopoulos V, Pentheroudakis G (2012) Long-term survivors among patients with cancer of unknown primary. Crit Rev Oncol Hematol 84(1):85–92PubMedCrossRef

Pentheroudakis G, Stoyianni A, Pavlidis N (2011) Cancer of unknown primary patients with midline nodal distribution: midway between poor and favourable prognosis? Cancer Treat Rev 37:120–126PubMedCrossRef

Pentheroudakis G, Pavlidis N (2010) Serous papillary peritoneal carcinoma: unknown primary tumour, ovarian cancer counterpart or a distinct entity? A systematic review. Crit Rev Oncol Hematol 75:27–42PubMedCrossRef

Pentheroudakis G, Lazaridis G, Pavlidis N (2010) Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence. Breast Cancer Res Treat 119:1–11PubMedCrossRef

Barad O, Meiri E, Avniel A et al (2004) MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 14:2486–2494PubMedCrossRef

Varadhachary GR, Spector Y, Abbruzzese JL et al (2011) Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary. Clin Cancer Res 17:4063–4070PubMedCrossRef

10.

Meiri E, Mueller WC, Rosenwald S et al (2012) A second-generation microRNA-based assay for diagnosing tumor tissue origin. Oncologist 17:801–812PubMedCrossRef

11.

Nass D, Rosenwald S, Meiri E et al (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383PubMedCrossRef

12.

Benjamini Y, Drai D, Elmer G et al (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125:279–284PubMedCrossRef

13.

Clark-Langone KM, Sangli C, Krishnakumar J, Watson D (2010) Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX Colon Cancer Assay. BMC Cancer 10:691PubMedCrossRef

14.

Joh JE, Esposito NN, Kiluk JV et al (2011) The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist 16:1520–1526PubMedCrossRef

15.

Agullo-Ortuno MT, Lopez-Rios F, Paz-Ares L (2010) Lung cancer genomic signatures. J Thorac Oncol 5:1673–1691PubMedCrossRef

16.

Van Laar RK (2012) Genomic signatures for predicting survival and adjuvant chemotherapy benefit in patients with non-small-cell lung cancer. BMC Med Genomics 5:30PubMedCrossRef

17.

Cardoso F, Van’t Veer L, Rutgers E et al (2008) Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol 26:729–735PubMedCrossRef

18.

Ramaswamy S, Ross KN, Lander ES, Golub TR (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33:49–54PubMedCrossRef

19.

Bishop JF, Tracey E, Glass P, Jelfs P, Roder D (2007) Prognosis of subtypes of cancer of unknown primary compared to metastatic cancer. J Clin Oncol 25:18SCrossRef

20.

Luke C, Koczwara B, Karapetis C et al (2008) Exploring the epidemiological characteristics of cancers of unknown primary site in an Australian population: implications for research and clinical care. Aust N Z J Public Health 32:383–389PubMedCrossRef

21.

Greco FA, Oien K, Erlander M et al (2012) Cancer of unknown primary: progress in the search for improved and rapid diagnosis leading toward superior patient outcomes. Ann Oncol 23:298–304PubMedCrossRef

22.

Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R (2012) Molecular gene expression profiling to predict the tissue of Origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the sarah cannon research institute. J Clin Oncol doi:10.1200/JCO2012.43.3755

23.

Wang CM, Wang Y, Fan CG et al (2011) miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Biochem Biophys Res Commun 411:586–592PubMedCrossRef

24.

Mraz M, Malinova K, Kotaskova J et al (2009) miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities. Leukemia 23:1159–1163PubMedCrossRef

25.

Nigro A, Menon R, Bergamaschi A et al (2012) MiR-30e and miR-181d control radial glia cell proliferation via HtrA1 modulation. Cell Death Dis 3:e360PubMedCrossRef

26.

Lee JJ, Drakaki A, Iliopoulos D, Struhl K (2012) MiR-27b targets PPARgamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells. Oncogene 31:3818–3825PubMedCrossRef

27.

Thulasingam S, Massilamany C, Gangaplara A et al (2011) miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells. Mol Cell Biochem 352:181–188PubMedCrossRef

28.

Al-Nakhle H, Burns PA, Cummings M et al (2010) Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer. Cancer Res 70:4778–4784PubMedCrossRef

29.

Soon PS, Tacon LJ, Gill AJ et al (2009) miR-195 and miR-483-5p Identified as predictors of poor prognosis in adrenocortical cancer. Clin Cancer Res 15:7684–7692PubMedCrossRef

30.

Veronese A, Lupini L, Consiglio J et al (2010) Oncogenic role of miR-483-3p at the IGF2/483 locus. Cancer Res 70:3140–3149PubMedCrossRef

31.

Cloonan N, Brown MK, Steptoe AL et al (2008) The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition. Genome Biol 9:R127PubMedCrossRef

32.

Schneider B, Nagel S, Ehrentraut S et al (2012) Neoplastic MiR-17–92 deregulation at a DNA fragility motif (SIDD). Genes Chromosomes Cancer 51:219–228PubMedCrossRef

33.

Li L, Shi JY, Zhu GQ, Shi B (2012) MiR-17–92 cluster regulates cell proliferation and collagen synthesis by targeting TGFB pathway in mouse palatal mesenchymal cells. J Cell Biochem 113:1235–1244PubMedCrossRef

34.

Wu L, Chen Z, Zhang J, Xing Y (2012) Effect of miR-513a-5p on etoposide-stimulating B7–H1 expression in retinoblastoma cells. J Huazhong Univ Sci Technolog Med Sci 32:601–606PubMedCrossRef

35.

Lee LW, Zhang S, Etheridge A et al (2010) Complexity of the microRNA repertoire revealed by next-generation sequencing. RNA 16:2170–2180PubMedCrossRef

36.

Ripoli A, Rainaldi G, Rizzo M et al (2010) The fuzzy logic of microRNA regulation: a key to control cell complexity. Curr Genomics 11:350–353PubMedCrossRef

37.

Fizazi K, Greco FA, Pavlidis N et al. (2011) Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi64–68

Title: Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors
Authors: George Pentheroudakis
Yael Spector
Dimitrios Krikelis
Vassiliki Kotoula
Eti Meiri
Vassiliki Malamou-Mitsi
George Fountzilas
Mats Sanden
Nicholas Pavlidis
Hila Benjamin
Ranit Aharonov
Publication date: 01-04-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 4/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-012-9548-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2013

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of intrathoracic lymph node metastases from extrathoracic malignancies

Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus

Liver-directed chemotherapy of cetuximab and bevacizumab in combination with oxaliplatin is more effective to inhibit tumor growth of CC531 colorectal rat liver metastases than systemic chemotherapy

Combined effect of dehydroxymethylepoxyquinomicin and gemcitabine in a mouse model of liver metastasis of pancreatic cancer

LIM kinase inhibition reduces breast cancer growth and invasiveness but systemic inhibition does not reduce metastasis in mice

Integrin α3β1 regulates tumor cell responses to stromal cells and can function to suppress prostate cancer metastatic colonization

Keynote webinar | Spotlight on antibody–drug conjugates in cancer