The P2X7 receptor: a novel biomarker of uterine epithelial cancers.
OBJECTIVE
To determine expression of the P2X(7) receptor in normal and in cancer uterine tissues. The rationale was that the receptor P2X(7) regulates constitutive apoptosis in uterine epithelial cells, and previous studies showed diminished P2X(7)-mediated apoptosis in cancer uterine cells compared with normal cells.


METHODS
A clinical, experimental feasibility study. Normal (n = 42) and cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to 75. End points for P2X(7) mRNA were quantitative PCR and in situ hybridization, and end points for P2X(7) protein were Western blots and immunostaining using anti-P2X(7) antibody.


RESULTS
(a) In normal uteri, P2X(7) mRNA and protein were expressed predominantly in the epithelial (endometrial, endocervical, and ectocervical) cells. (b) Expression of the P2X(7) mRNA and protein was absent from endometrial and endocervical adenocarcinoma tissues and from cervical squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X(7) protein was absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X(7) mRNA (normalized in each tissue to the constitutive glyceraldehyde-3-phosphate dehydrogenase) and P2X(7) protein levels (normalized in each tissue to the constitutive tubulin) revealed that P2X(7) mRNA and/or protein levels can distinguish uterine normal from cancer tissues at high degrees of sensitivity (92%, 100%) and specificity (100%, 90%).


CONCLUSIONS
(a) Levels of the P2X(7) are lower in uterine epithelial cancer tissues than in the corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and protein levels could be used as a novel biomarker to differentiate normal and cancer uterine epithelial tissues.
Li
Xin
X
Department of Reproductive Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Zhou
Lingying
L
Feng
Ying-Hong
YH
Abdul-Karim
Fadi W
FW
Gorodeski
George I
GI
D000230:Adenocarcinoma / Q000737:chemistry; D000236:Adenoma / Q000737:chemistry; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000737:chemistry; D016022:Case-Control Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000737:chemistry; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018048:Receptors, Purinergic P2 / Q000032:analysis*; D058486:Receptors, Purinergic P2X7; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000737:chemistry; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C546468:P2RX7 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7