A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients

Leandersson, Pia; Åkesson, Anna; Hedenfalk, Ingrid; Malander, Susanne; Borgfeldt, Christer

doi:10.1371/journal.pone.0240418

Cited by 21 publications

(24 citation statements)

References 51 publications

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“…In the analysis of women who developed ovarian cancer less than 9 months after blood draw, nine biomarkers showed potentially useful discrimination, with AUC ≥ 0.70. Besides the well-established markers CA125 and HE4, four other markers in this list: (FR-alpha, KLK11, MDK and CXCL13) had been highlighted previously as having discrimination potential in several prior case-control comparisons using the Olink® Multiplex platforms [ 8 – 12 , 15 ], as well as in some further studies using other platforms [ 16 – 18 ]. We did not observe meaningful improvements in diagnostic performance by adding a single markers to CA125, particularly for ovarian cancer diagnosed more than 9 months after blood sampling.…”

Section: Discussionmentioning

confidence: 99%

“…Olink® Proteomics has developed a technology based on the proximity extension assay (PEA) [ 6 , 7 ], which permits the simultaneous measurement of up to 92 proteins in microliter volumes of blood serum or plasma. Several recent studies have used this multiplex platform to identify biomarkers for ovarian cancer detection, measuring candidate markers in blood samples collected from patients with clinically manifest ovarian cancer and from healthy controls or patients with benign pelvic conditions [ 8 – 12 ]. Using various (only partially overlapping) Olink® assay panels for sets of proteins relevant in oncology, inflammation and other disease areas, these studies identified several candidate proteins that, alone or in multi-marker panels, showed good discrimination between ovarian cancer patients and women with benign conditions or healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

et al. 2022

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Background CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. Results Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. Conclusion Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

et al. 2022

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“…High expression of ITGAV in ovarian cancer tumor tissue from late stage tumors has been associated with poor prognosis [37]. However, both tissue [38] and serum levels of ITGAV have been shown to be present at reduced levels in ovarian cancer compared to benign tumors and borderline ovarian cancers [39]. In addition, ITGAV expression has been correlated with increased expression of the matrix metalloprotease MMP9 in ovarian cancer effusions [40], which could impact ITGAV shedding into the serum in late stage ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Development of a Multiprotein Classifier for the Detection of Early Stage Ovarian Cancer

Boylan

Petersen

Starr

et al. 2022

Cancers

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Background: Individual serum biomarkers are neither adequately sensitive nor specific for use in screening the general population for ovarian cancer. The purpose of this study was to develop a multiprotein classifier to detect the early stages of ovarian cancer, when it is most treatable. Methods: The Olink Proseek Multiplex Oncology II panel was used to simultaneously quantify the expression levels of 92 cancer-related proteins in sera. Results: In the discovery phase, we generated a multiprotein classifier that included CA125, HE4, ITGAV, and SEZ6L, based on an analysis of sera from 116 women with early stage ovarian cancer and 336 age-matched healthy women. CA125 alone achieved a sensitivity of 87.9% at a specificity of 95%, while the multiprotein classifier resulted in an increased sensitivity of 91.4%, while holding the specificity fixed at 95%. The performance of the multiprotein classifier was validated in a second cohort comprised of 192 women with early stage ovarian cancer and 467 age-matched healthy women. The sensitivity at 95% specificity increased from 74.5% (CA125 alone) to 79.2% with the multiprotein classifier. In addition, the multiprotein classifier had a sensitivity of 95.1% at 98% specificity for late stage ovarian cancer samples and correctly classified 80.5% of the benign samples using the 98% specificity cutpoint. Conclusions: The inclusion of the proteins HE4, ITGAV, and SEZ6L improved the sensitivity and specificity of CA125 alone for the detection of early stages of ovarian cancer in serum samples. Furthermore, we identified several proteins that may be novel biomarkers of early stage ovarian cancer.

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“…Combinations of biomarkers, such as circulating miR-19a-3p and miR-483-5p, can enhance the diagnostic performance in various cancer types (59)(60)(61)(62). Notably, Chen et al (18) recently demonstrated that miR-650 combined with CA211 could be an effective diagnostic indicator for screening of the incidence of GC.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of circulating microRNA‑130b and blood routine parameters in the early diagnosis of gastric cancer

et al. 2021

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Patients with gastric cancer (GC) have a poor prognosis, which is mainly due to the low rate of early diagnosis. The present study aimed to evaluate whether circulating microRNA-130b (miR-130b) and blood routine parameters [neutrophil count (N#), lymphocyte count (L#), monocyte count (M#), neutrophil percentage (N%), lymphocyte percentage (L%), monocyte percentage (M%), hemoglobin (Hb) level, hematocrit (Hct), red blood cell distribution width (RDW), platelet count, platelet distribution width (PDW), mean platelet volume (MPV), MPV to platelet count ratio (MPV/PC), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR)] are useful biomarkers for GC, early stage GC (EGC) and precancerous lesion (Pre) detection, and to identify more effective diagnostic models by combining circulating blood markers. Circulating levels of M#, M%, RDW-coefficient of variation (RDW-CV), MPV, PDW, MLR and NLR were significantly higher, and the levels of Hb and L% were significantly lower in patients with GC and Pre compared with those in healthy controls (NCs) (all P<0.05). The N#, N% and PLR in patients with GC were significantly higher and the Hct was significantly lower than those in the NCs (all P<0.05). The values of MPV/PC were significantly higher in the Pre cohort compared with those in the NCs. The area under the curve (AUC) of the receiver operating characteristic curve of potential biomarkers for GC was 0.634–0.887 individually, and this increased to 0.978 in the combination model of miR-130b-PDW-MLR-Hb. Additionally, the values for RDW-CV, PLR, NLR, N# and N% were positively correlated with cancer stage, while the values for MPV, L#, L%, Hb and Hct were negatively correlated with cancer stage. Furthermore, the circulating levels of miRNA-130b, and the values for NLR, RDW-CV, PDW, M%, red blood cell count, Hct, Hb and MLR differed between the EGC and NC groups. The AUC values of these biomarkers were 0.6491–0.911 individually in the diagnosis of EGC, and these increased to 0.960 in combination. In addition, the AUC values for miR-130b, RDW-CV, MPV/PC ratio, MLR, NLR, PDW, L%, M%, M# and Hb in the diagnosis of Pre were 0.638–0.811 individually. The dual-model of miR-130b-PDW manifested the largest AUC of 0.896 in the diagnosis of Pre, and the sensitivity and accuracy were increased when miR-130b and PDW were combined. All these results suggested that circulating miR-130b and blood routine parameters might be potential biomarkers, and combinations of measurements of these biomarkers may improve the GC, EGC and Pre diagnostic accuracy.

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A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients

Cited by 21 publications

References 51 publications

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Development of a Multiprotein Classifier for the Detection of Early Stage Ovarian Cancer

Efficacy of circulating microRNA‑130b and blood routine parameters in the early diagnosis of gastric cancer

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