High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma.
BACKGROUND
Claudin-7 (CLDN-7) is a tight junction protein that has been shown overexpressed in several human cancers. We investigated prognostic significance of CLDN-7 overexpression in patients with epithelial ovarian carcinoma (EOC) and its functional role on cell proliferation in ovarian carcinoma cell lines.


METHODS
CLDN-7 expression was evaluated by real-time RT-PCR and immunohistochemical analysis in 71 patients with EOC. We assessed the association of CLDN-7 expressions with prognosis of the patients including sensitivity to platinum-based chemotherapy. In vitro experiment was performed with and without inhibition of CLDN-7 by its siRNA to evaluate the sensitivity of the human ovarian cancer cells to cisplatin chemotherapy.


RESULTS
CLDN-7 transcripts in EOCs were significantly up-regulated compared with normal ovarian tissues (P<0.001). The expression of CLDN-7 protein was observed in majority (69/71, 97.1%) of the EOCs but not in normal ovarian tissues (P<0.001). High CLDN-7 expression in primary tumour correlated with shorter progression-free survival (PFS) of the patients (P=0.005) and poor sensitivity to platinum-based chemotherapy (P=0.024). Moreover, CLDN-7 was highly expressed in 2774 and HeyA8 human ovarian cancer cells and inhibition of CLDN-7 by its siRNA significantly enhanced the sensitivity of 2774 and HeyA8 cells to cisplatin treatment.


CONCLUSIONS
These findings suggest CLDN-7 expression is an independent prognostic factor for PFS and it may play a role in regulating response to platinum-based chemotherapy in the treatment of EOC.
Department of Obstetrics and Gynecology, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
Chul Jung
CJ
Kim
Jeong-Won
JW
Lee
Jung-Joo
JJ
Choi
Hye Young
HY
Choi
Young-Ae
YA
Park
Hye-Kyung
HK
Jeon
Chang Ohk
CO
Sung
Sang Yong
SY
Song
Yoo-Young
YY
Lee
Chel Hun
CH
Choi
Tae-Joong
TJ
Kim
Je-Ho
JH
Lee
Byoung-Gie
BG
Kim
Duk-Soo
DS
Bae
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D057167:Claudins; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C473255:CLDN7 protein, human; D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002945:Cisplatin