4.6 Article

An immature inhibin-α-expressing subpopulation of ovarian clear cell carcinoma cells is related to an unfavorable prognosis

Journal

CANCER MEDICINE
Volume 10, Issue 5, Pages 1485-1500

Publisher

WILEY
DOI: 10.1002/cam4.3801

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Funding

  1. Japan Society for the Promotion of Science [A19H034520, T19K165570, T19K165850, T20K161710, T20K162200]

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The study found that inhibin-alpha expressing OCCC tumor cells in ovarian tumors exhibit distinct features, including lower proliferation, immaturity, and acceleration of malignant progression.
Inhibin-alpha, a member of transforming growth factor-beta, is elevated in multiple tumors, but its specific roles are poorly understood. Here, we examined the feature of inhibin-alpha-expressing cells in ovarian tumors. Immunohistochemically, inhibin-alpha-expressing tumor cells were detected only in ovarian clear cell carcinoma (OCCC) among various types of ovarian tumors. By comparing the expression of inhibin-alpha and Ki-67, inhibin-alpha-expressing tumor cells were revealed to be less proliferative. When spheroids and chemoresistant cells were derived from OCCC cell lines, the expression level of inhibin-alpha was elevated, and that of an immature marker, aldehyde dehydrogenase, was also elevated. In consistent with this, inhibin-alpha expression was correlated with other immature markers, such as OCT3/4 and SOX2, and inversely correlated with proliferative marker MKI67 in public database on OCCC. Knockdown of inhibin-alpha in OCCC cell decreased chemoresistance. Moreover, prognostic analysis with 69 surgically resected OCCC cases revealed that the increased inhibin-alpha expression was an independent unfavorable prognostic factor. These findings suggested that inhibin-alpha-expressing subpopulation of OCCC tumor cells appeared to be less proliferative, immature, and angiogenic and to be related to acceleration of malignant progression.

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