Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study

Yin, Mingzhu; Tan, Shan; Li, Xia; Hou, Yan; Cao, Guosheng; Li, Kang; Kou, Junping; Lou, Ge

doi:10.1007/s13277-015-4164-x

Cited by 45 publications

(37 citation statements)

References 29 publications

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“…In cell culture models, the HPV-16 E7 oncoprotein has been shown to stimulate production and activation of phospholipase D, resulting in PA production, which stimulates the mTOR pathway, promoting cell proliferation (51). PA is generated through hydrolysis of PC, which has similarly been shown to be up-regulated in cervical cancer tissues (52). PI is a critical component of the PI3K/AKT/mTOR signaling pathway and aberrant signaling through this pathway is crucial for the ongoing growth and survival of numerous cancers and is a poor prognostic indicator (53).…”

Section: Discussionmentioning

confidence: 99%

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Tzafetas

Mitra

Paraskevaidi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.REIMS | cervical cancer | mass spectrometry | iKnife | fertility preservation

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Section: Discussionmentioning

confidence: 99%

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Tzafetas

Mitra

Paraskevaidi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…A previous study showed that significant differences in serum levels of PC and fatty acids between advanced prostate cancer cases and controls [ 29 ]. Yin et al utilized PC combined with LysoPC to predict the occurrence of cervical cancer and got an AUC value of 0.97 [ 30 ]. Uchiyama et al identified PC(16:0/16:1) and PC(18:1/20:4) could discriminate the border between the cancer and stromal regions of OSCC [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma lipid profiling and diagnostic biomarkers for oral squamous cell carcinoma

Wang

Liu

et al. 2017

Oncotarget

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Biological requirements for tumor cell proliferation include the sustained increase of structural, energetic, signal transduction and biosynthetic precursors. Because lipids participate in membrane construction, energy storage, and cell signaling. We hypothesized that the differences in lipids between malignant carcinoma and normal controls could be reflected in the bio-fluids. A total of 100 pre-operative plasma samples were collected from 50 oral squamous cell carcinoma (OSCC), 50 normal patients and characterize by lipid profiling using ultra performance liquid chromatography/electro spray ionization mass spectrometry (UPLC-MS). The lipid profiles of the OSCC and control samples as well as the different stages were compared. Differentially expressed lipids were categorized as glycerophospholipids and sphingolipids. All glycerophospholipids were decreased, especially phosphatidylcholine and phosphoethanolamine plasmalogens, whereas sphingolipids were increased in the OSCC patients compared to the controls. We further identified 12 staging related lipids, which could be utilized to discriminate early stage patients from advanced stage patients. In the future, the differential lipids may provide biologists with additional information regarding lipid metabolism and guide clinicians in making individualized therapeutic decisions if these results are confirmed in a larger study.

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“…Previous studies have indicated that a combination of several variants generally provides an improved diagnostic power for ROC analysis compared with ROC analysis of individual markers (38)(39)(40)(41). A combination of several biomarkers may therefore improve the diagnostic results for tumors, as has been demonstrated in thyroid cancer (42).…”

Section: Itga3 Itga5 Itgb1 Itgb6 N ----------------------------------mentioning

confidence: 99%

Evaluation of the mRNA expression levels of integrins α3, α5, β1 and β6 as tumor biomarkers of oral squamous cell carcinoma

et al. 2018

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Integrin signaling may modulate several different functions involved in cell migration, invasion, proliferation and motility, and is a potential candidate biomarker for oral cancer. In the present study, a total of four integrin genes were evaluated as potential biomarkers of oral squamous cell carcinoma (OSCC). Gene expression was determined using the reverse transcription-quantitative polymerase chain reaction in 55 OSCC and 55 matched normal oral tissues. The performance of individual and combined biomarkers was analyzed by receiver operating characteristic (ROC) analysis based on the relative mRNA expression (OSCC vs. matched oral tissue from the tumor-free margin), which was calculated using the ΔΔCq value (ΔCq of OSCC-ΔCq of oral tissue from the tumor-free margin of the same patient). In the individual ROC analysis, the areas under the ROC curve (AUCs) of relative mRNA expression (ΔΔCq) of integrin subunit α3 (ITGA3), integrin subunit α5 (ITGA5), integrin subunit β1 (ITGB1) and integrin subunit β6 (ITGB6) in all tumor locations were 0.724, 0.698, 0.640 and 0.657, respectively. For locations 2 (tongue/mouth part) and 3 (edentulous ridge), their individual AUC values were 0.840, 0.765, 0.725 and 0.763, respectively. In the cumulative ROC analysis, ITGA3, ITGA5 and ITGB1 genes exhibited the highest combined AUC values (0.809 and 0.871 for all locations and locations 2 and 3 combined, respectively) compared with other biomarker combinations. In conclusion, the results of the present study identified that higher mRNA expressions of ITGA3, ITGA5, ITGB1 and ITGB6 genes are suitable for OSCC diagnosis biomarkers. Cumulative ROC analysis indicated an improved overall performance compared with the best individual integrin biomarker of OSCC.

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Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study

Cited by 45 publications

References 29 publications

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Plasma lipid profiling and diagnostic biomarkers for oral squamous cell carcinoma

Evaluation of the mRNA expression levels of integrins α3, α5, β1 and β6 as tumor biomarkers of oral squamous cell carcinoma

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