A novel serum metabolome score for breast cancer diagnosis

Rashed, Ramzy E.; Darwish, Hossam; Omran, Mohamed M.; Belal, A.A.M.; Zahran, Faten

doi:10.1080/09674845.2020.1784568

Cited by 9 publications

(10 citation statements)

References 35 publications

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“…Given the high prevalence of breast cancer in females, circulating levels of C3DC, C4, C10:1, and C10:2 may have large clinical implications for breast cancer diagnosis as well as potentially risk assessment and treatment. Similar conclusions regarding study implications have also been conveyed by previous studies ( 6 , 7 , 9 , 10 ). Further, carnitine levels can be modified via the consumption of animal-based products and l-carnitine supplements ( 28 , 29 ).…”

Section: Discussionsupporting

confidence: 88%

Circulating Carnitine Levels and Breast Cancer: A Matched Retrospective Case-Control Study

Zhang

Zhu

et al. 2022

Front. Oncol.

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IntroductionEpidemiological studies investigating the association between carnitine and breast cancer are scarce.Materials and MethodsThis 1:1 age-matched retrospective case-control study identified 991 female breast cancer cases and 991 female controls without breast cancer using pathological testing. We used targeted metabolomics technology to measure 16 types of whole blood carnitine compounds, such as free carnitine (C0) and octadecanoylcarnitine (C18).ResultsThe average age for cases and controls was approximately 50 ± 8.7 years. After adjusting for covariates, each standard deviation (SD) increase in malonylcarnitine (C3DC; OR 0.91; 95% CI 0.83-1.00), decenoylcarnitine (C10:1; OR 0.87; 95% CI 0.79-0.96), and decadienoylcarnitine (C10:2; OR 0.90; 95% CI 0.82-0.99) level was associated with decreased odds of breast cancer. However, higher butyrylcarnitine (C4) levels were associated with increased odds of breast cancer (OR 1.12; 95% CI 1.02-1.23). No statistically significant relationship was noted between other carnitine compounds and breast cancer. The false discovery rates for C3DC, C4, C10:1 and C10:2 were 0.172, 0.120, 0.064 and 0.139, respectively.ConclusionsHigher levels of C3DC, C10:1, and C10:2 were protective factors for breast cancer, whereas increased C4 levels were a risk factor for the disease.

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Section: Discussionsupporting

confidence: 88%

Circulating Carnitine Levels and Breast Cancer: A Matched Retrospective Case-Control Study

Zhang

Zhu

et al. 2022

Front. Oncol.

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“…CA153 and CEA are the most frequently evaluated serum biomarkers for breast cancer detection. However, only 50% of breast cancers are detected based on the CA153 or CEA levels [ 39 ]. The sensitivity, specificity, PPV, and NPV of CA153 and CEA (52.8%, 61.4%, 56.1%, and 56.8%; 69.1%, 49.3%, 62.5%, and 51.2%, respectively) were lower than those of the serum SEMA4C levels.…”

Section: Discussionmentioning

confidence: 99%

Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study

Wang

Qiao

Yang

et al. 2021

Cancer Communications

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Background To date, there is no approved blood‐based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. Methods We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan‐cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre‐treatment serum SEMA4C levels, measured using optimized in‐house enzyme‐linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post‐surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. Results We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900–0.941) and 0.932 (95%CI: 0.911–0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early‐stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916–0.946) and 0.879 (95%CI: 0.832–0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. Conclusions Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

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“…A panel of seven metabolites (Glu, Orn, Thr, Trp, Met-SO, C2, and C3) in the plasma could detect breast cancer with an AUC of 0.87 in the training cohort (80 cancer vs. 100 healthy controls) and an AUC of 0.80 in the validation cohort (109 cancer vs. 50 healthy controls) [ 32 ]. The expression levels of three metabolites (8-hydroxy-2ʹ-deoxyguanosine, 1-methylguanosine, and 1-methyl adenosine), together with CA15-3, could achieve 88.8% sensitivity and 86.8% specificity in the detection of early-stage breast cancer based on a serum metabolome score [ 33 ]. In a prospective case–control study, the signature of seven metabolites (dimethyldodecane, galactose, α-glyceryl stearate, methyl stearate, 1(1-methoxycarbonyethyl)-4-(2-methyl-2-trimethylsilyl-oxypropyl) benzene, tetradecane, and glucopyranoside) in serum revealed a distinct separation between healthy controls and breast cancer patients at a sensitivity of 96% and a specificity of 100% [ 34 ].…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

Non-Invasive Biomarkers for Early Detection of Breast Cancer

Guan

Fan

et al. 2020

Cancers

135

104

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Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

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A novel serum metabolome score for breast cancer diagnosis

Cited by 9 publications

References 35 publications

Circulating Carnitine Levels and Breast Cancer: A Matched Retrospective Case-Control Study

Circulating Carnitine Levels and Breast Cancer: A Matched Retrospective Case-Control Study

Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study

Non-Invasive Biomarkers for Early Detection of Breast Cancer

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