Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients

Abstract

We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.

Human papilloma virus: Apprehending the link with carcinogenesis and unveiling new research avenues (Review)

“…In both serum and plasma, the osteopontin level was significantly higher compared to healthy subjects, and was reported as having the highest values in stage III–IV. However, as osteopontin can exist in a truncated form and thus, the target epitope recognized by the monoclonal antibody may be absent, further studies are warranted to investigate the mechanisms through which the entire molecule and/or its fragments play a role in cervical cancer biology ( 125 ).…”

Biological and Clinicopathological Characteristics of OPN in Cervical Cancers

“…OPN is a phosphorylated glycoprotein that bridges cell and matrix inorganic substances and is closely associated with the occurrence, progression and metastasis of malignant tumors ( Le et al, 2003 ; Vergis et al, 2008 ; Raja et al, 2014 ; Ostheimer et al, 2017 ; Cao et al, 2019 ; Nishio et al, 2021 ). Recently, certain studies have indicated that OPN is a diagnostic and prognostic biomarker for CC ( Cho et al, 2008 ; Leung et al, 2016 ). OPN expression was found to be positively related to FIGO stage, tumor size and cisplatin resistance ( Cho et al, 2008 ; Chen et al, 2019 ).…”

Sensor detection in gynaecological medicine

“…Other protein biomarkers include osteopontin (OPN), 110 protein cyclin-dependent kinase inhibitor (p16), and topoisomerase II-alpha (TOP2A). 111 OPN was observed to be upregulated in cervical cancer, 110 while p16 and TOP2A overexpression were related to precancer and cancer.…”

“…Other protein biomarkers include osteopontin (OPN), 110 protein cyclin-dependent kinase inhibitor (p16), and topoisomerase II-alpha (TOP2A). 111 OPN was observed to be upregulated in cervical cancer, 110 while p16 and TOP2A overexpression were related to precancer and cancer. 111 However, OPN could only discriminate between healthy controls and advanced cervical cancer, suggesting OPN is effective as a late-stage biomarker for cervical cancer.…”