Purpose
We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers.
Materials and Methods
A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening.
Results
Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine.
Conclusion
MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.
Citations
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The chemosensitivity testing is important in the research of cancer biology, development and screening of anticancer drug, and improvement of chemotherapy modalities. Subrenal capsule tumor implant assay (SRCA) is a promising rapid method in the selection of individual chemotherapy for cancer patients clinically. A total of 100 SRCA were performed with several gynecologic malignancies(69 cervical, 10 ovarian, 10 endometrial carcinomas, 6 vulva carcinoma, 4 sarcoma, and 1 choriocarcinoma). 1 mm x 1 mm x 1 mm fragments oi fresh human gynenologic tumors were implanted under the renal capsule of immunocompetent female adult BALB-C mice and tested against several chemotherapeutic agents or their combinations. An average of 75% of tumors showed positive growth. The evaluable assay rate was 91%(91/100). Variable response rate were noted in each gynenologic tumor. An overall predictive accuracy rate of SRCA was 73% in present series. In conclusion, the SRCA is considered as a reliable in vivo clinical chemosensitivity test in the selection of individual cancer chemotherapy.