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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 13 of 27

one of the 10 top score genes of the signature. The prognostic power of FXYD5 was also successfully
validated, both at mRNA and protein level by RT-qPCR and IHC, respectively on the training and validation
sets. Moreover, FXYD5 overexpression was significantly associated with platinum resistance and cancer
progression.

Conclusion: We demonstrated the consistent overexpression of FXYD5 in HGSOC short-term survivors
compared to long-term ones. FXYD5 may become a useful predictive marker for a more accurate selection
of HGSOC patients for adjuvant treatments, and a possible target for antibody-drug conjugated anticancer
agents, as recently demonstrated for thyroid cancer cell lines.

18. Claudin-7 downregulation is predictive of distant metastases in high-grade serous ovarian

carcinoma patients

1
4
2
1
3
Chiara Romani , Valentina Zizioli , Marco Silvestri , Michela Corsini , Laura Ardighieri , Paola
5
6
Todeschini , Sergio Marchini , Maurizio D’Incalci , Laura Zanotti , Antonella Ravaggi , Franco
5
6
5
2,
2
7
1
2
Odicino , Enrico Sartori , Alessandro Davide Santin , Stefania Mitola , Eliana Bignotti *, Stefano
Calza *
8,
1 Department of Molecular and Translational Medicine, University of Brescia, Brescia 25121, Italy.
2 Division of Gynecologic Oncology, ASST Spedali Civili, Brescia 25123, Italy.
3 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Department of Applied Research and
Technological Development, Biomarkers Unit, Milan 20133, Italy.
4 Department of Pathology, ASST Spedali Civili di Brescia, Brescia 25123, Italy.
5 “Angelo Nocivelli” Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia,
Brescia 25121, Italy.
6 Department of Oncology, IRCCS, “Mario Negri” Institute for Pharmacological Research, Milan 20156, Italy.
7 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333
Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
8 Department of Molecular and Translational Medicine, Unit of Biostatistics and Bioinformatics, University of
Brescia, Brescia 25121, Italy.
*Equal contribution.
Introduction: High-grade serous carcinoma (HGSOC) is the most frequent and lethal ovarian carcinoma
histotype. Although the abdominal dissemination is considered the most common, distant metastases
occur in about 30% of patients with newly diagnosed or recurrent HGSOC. No tumor marker can currently
predict the risk of distant metastasis in HGSOC. Tight-junction protein claudin-3, -4 and -7 are frequently
dysregulated in HGSOC and functionally related to cancer progression to a metastatic disease. Here we
analyze claudin-3, -4 and -7 expression as markers of distant metastasis.

Experimental model: Claudin expression was evaluated in 105 primary HGSOC tissues, 14 normal ovarian
and 26 normal fallopian tube epithelia by quantitative RT-PCR and immunohistochemistry, and correlated
with clincopathological features. Gene set enrichment analysis was performed on microarray-generated gene
expression data to investigate key pathways in patients with distant metastasis.

Results: Claudin-3, -4 and -7 expression levels are decreased in HGSOC compared to normal tubal
epithelium, currently considered alternative source of such tumors. Decreased expression of claudin-7 is
seen in tumors from women who develop distant recurrence (P = 0.016), mainly by hematogenous route (P
= 0.025). The estimated reduction in the probability of distant disease is of 39% per unit increase in the level