The purpose of the study was to investigate the role of Prolactin-Induced Protein
(PIP) as a predictive biomarker for Keratoconus (KC). This study included one hundred
and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls
(27 male, 33 female). Tears, plasma and saliva samples were collected from all participants.
In both KC and healthy groups all collected samples were divided into four age subgroups
(15–24y), (25–34y), (35–44y) and (45y and up). Samples were analyzed using western
blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver
operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy
for distinguishing between KC and healthy eyes. Difference in PIP protein levels between
patients with KC and healthy controls. Results showed significant downregulation of
PIP expression in all three biological fluids on KC patients when compared to healthy
controls, independent of age, sex and severity. Since PIP is a hormonal-regulated
protein, we also investigated the expression of major sex hormones. We detected significant
upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels
and significant downregulation of estrone and estriol levels, in KC patients compared
to healthy controls, independent of sex, age, and KC severity stage. ROC was used
to determine the overall predictive accuracy of this protein in KC. Data showed an
area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902–0.971), in plasma
of 0.928 (95%CI: 0.890–0.968) and in saliva of 0.929 (95%CI: 0.890–0.968). Conclusively,
our results show that PIP levels are reduced in all three human biological fluids
tested, and may independently or in combination with current imaging techniques aid
in screening and diagnosis of KC. Our data revealed that PIP levels can potentially
differentiate between disease and healthy cases, and PIP levels are stable in relation
to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation
with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology
and highlights the role of PIP as a KC biomarker.