Nanomaterials assisted laser desorption ionization for differential diagnosis of ovarian cancer and benign ovarian tumors

A lack of sensitive and specific tumor markers for early diagnosis and treatment is a major cause for the high mortality rate of ovarian cancer. The purpose of this study was to identify potential proteomics-based biomarkers useful for the differential diagnosis between ovarian cancer and benign pelvic masses. Serum samples from 41 patients with ovarian cancer, 32 patients with benign pelvic masses, and 41 healthy female blood donors were examined, and proteomic profiling of the samples was assessed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy (MS). A confirmatory study was also conducted with serum specimens from 58 patients with ovarian carcinoma, 37 patients with benign pelvic masses, and 48 healthy women. A classification tree was established using Biomarker Pattern Software. Six differentially expressed proteins (APP, CA 125, CCL18, CXCL1, IL-8, and ITIH4) were separated by high-performance liquid chromatography and identified by matrix-assisted laser desorption/ionization (MALDI)-MS/MS and database searches. Two of the proteins overexpressed in ovarian cancer patients, chemokine CC2 motif ligand 18 (CCL18) and chemokine CXC motif ligand 1 (CXCL1), were automatically selected in a multivariate predictive model. These two protein biomarkers were then validated and evaluated by enzyme-linked immunosorbent assay (ELISA) in 535 serum specimens (130 ovarian cancer, 64 benign ovarian masses, 36 lung cancer, 60 gastric cancer, 55 nasopharyngeal carcinoma, 48 hepatocellular carcinoma, and 142 healthy women). The combined use of CCL18 and CXCL1 as biomarkers for ovarian cancer had a sensitivity of 92% and a specificity of 97%. The multivariate ELISA analysis of the two putative markers in combination with CA 125 resulted in a sensitivity of 99% for healthy women and 94% for benign pelvic masses, and a specificity of 92% for both groups; these values were significantly higher than those obtained with CA 125 alone (P<0.05). We conclude that serum CCL18 and CXCL1 are potentially useful as novel circulating tumor markers for the differential diagnosis between ovarian cancer and benign ovarian masses.

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FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

Endocrine Related Cancer ◽

10.1677/erc.0.0110315 ◽

2004 ◽

Vol 11 (2) ◽

pp. 315-321 ◽

Cited By ~ 23

Author(s):

I Rzepka-G√≥rska ◽

A Chudecka-G≈Çaz ◽

B Kosmowska

Keyword(s):

Ovarian Cancer ◽

Differential Diagnosis ◽

Malignant Tumors ◽

Ovarian Tumors ◽

Predictive Values ◽

Epithelial Tumors ◽

Ovarian Carcinogenesis ◽

Benign Ovarian Tumors ◽

Sensitivity Specificity

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.

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Peritoneal Fluid Cytokines and the Differential Diagnosis of Benign and Malignant Ovarian Tumors and Residual/Recurrent Disease Examination

The International Journal of Biological Markers ◽

10.1177/172460080702200302 ◽

2007 ◽

Vol 22 (3) ◽

pp. 172-180 ◽

Cited By ~ 8

Author(s):

M. Chechlinska ◽

J. Kaminska ◽

J. Markowska ◽

A. Kramar ◽

J. Steffen

Keyword(s):

Ovarian Cancer ◽

Differential Diagnosis ◽

Cancer Patients ◽

Peritoneal Fluid ◽

Recurrent Disease ◽

Ovarian Tumors ◽

Therapy Outcome ◽

Ca 125 ◽

Benign Ovarian Tumors ◽

Local Cytokine

This study aimed to assess the potential value of peritoneal fluid cytokine examination for the differential diagnosis of ovarian tumors and for evaluating residual or recurrent disease after treatment. The cytokines that are commonly elevated in ovarian cancer, VEGF, IL-6, bFGF, IL-8 and M-CSF, and a reference ovarian tumor marker, CA 125, were measured in peritoneal fluids of 53 previously untreated patients with epithelial ovarian cancer, 18 ovarian cancer patients after surgical treatment and chemotherapy, and 17 patients with benign epithelial ovarian tumors. Non-parametric statistical analysis of data was performed. Ovarian cancer peritoneal fluids, as compared to peritoneal fluids of patients with benign ovarian tumors, contained significantly higher concentrations of IL-6, VEGF and CA 125, and significantly lower concentrations of bFGF and M-CSF, but only the levels of IL-6 and VEGF were significantly higher in peritoneal fluids of stage I and II ovarian cancer patients than of patients with benign ovarian conditions. IL-6 at the cutoff level of 400 pg/mL discriminated benign and malignant ovarian tumors with 92% sensitivity and 60% specificity, while VEGF at the cutoff of 400 pg/mL had 90% sensitivity and 80% specificity. At the cutoff level of 1200 pg/mL, IL-6 had 84% sensitivity and 87% specificity. A radical decrease in local cytokine and CA 125 levels in patients after treatment was independent of therapy outcome. IL-6 and VEGF measurements in peritoneal fluids might be useful for the differential diagnosis of malignant and benign ovarian conditions, but not for residual or recurrent disease examination.

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Urine proteome analysis by C18 plate–matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows noninvasive differential diagnosis and prediction of diabetic nephropathy

PLoS ONE ◽

10.1371/journal.pone.0200945 ◽

2018 ◽

Vol 13 (7) ◽

pp. e0200945 ◽

Cited By ~ 4

Author(s):

Chao-Jung Chen ◽

Wen-Ling Liao ◽

Chiz-Tzung Chang ◽

Hsin-Yi Liao ◽

Fuu-Jen Tsai

Keyword(s):

Mass Spectrometry ◽

Differential Diagnosis ◽

Proteome Analysis ◽

Laser Desorption ◽

Laser Desorption Ionization ◽

Ionization Time ◽

Desorption Ionization ◽

Flight Mass Spectrometry ◽

Matrix Assisted Laser ◽

Matrix Assisted Laser Desorption

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Alteration in Lipid and Protein Profiles of Ovarian Cancer: Similarity to Breast Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e318226c5f5 ◽

2011 ◽

Vol 21 (9) ◽

pp. 1566-1572 ◽

Cited By ~ 15

Author(s):

Sokbom Kang ◽

Aera Lee ◽

Young Seung Park ◽

Seok Cheol Lee ◽

Sang Yoon Park ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Laser Desorption ◽

Lipid Profiles ◽

Laser Desorption Ionization ◽

Protein Profiles ◽

Tissue Samples ◽

Desorption Ionization ◽

Matrix Assisted Laser ◽

Matrix Assisted Laser Desorption

AbstractThis study was undertaken to evaluate protein and lipid profiles of ovarian cancer tissue samples. Twenty-three frozen ovarian cancer samples and 6 adjacent normal samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization mass spectrometry. Sinapinic acid and 2, 5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify protein and lipid profiles respectively, and mass spectra were acquired using a matrix-assisted laser desorption/ionization–time of flight instrument. Protein and lipid profiles classify 11 cancer and 3 adjacent normal samples in 100 random test sets with 92.9% median accuracy. Phosphatidylcholines {32:3} [M + Na]+ (m/z = 750.66), {34:1} [M + K]+ (m/z = 798.60), and {36:2} [M + K]+ (m/z = 824.56) were found to be increased in ovarian cancer. Interestingly, breast cancer–associated changes in lipid and protein profiles were also found in ovarian cancer. Thus, protein and lipid profiles accurately distinguish ovarian cancer from adjacent normal tissue samples. Common cancer-associated alterations in lipid and protein profiles were identified between ovarian and breast cancers.

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