Abstract
BackgroundLymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling.Material & methodsSerum samples of 60 cervical cancer patients (FIGO I/II) were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF) mass spectrometry (MS). Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO) validation for weighted Least Squares Support Vector Machines (LSSVM) was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI) and recurrent disease.ResultsLSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC) of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81), to predict recurrence (AUC 0.92), and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88), between squamous and adenosquamous carcinomas (AUC 0.85), and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94).ConclusionsPotential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.
Highlights
Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment
Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer
Identification of the potential biomarkers was hampered by the technical limitations of Surface-enhanced laser desorption (SELDI)-Time of flight (TOF) mass spectrometry (MS)
Summary
Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. In patients with early stage cervical cancer, the treatment of choice is either surgical, including radical hysterectomy and pelvic LN dissection, or chemoradiation. Combining both treatments leads to a higher morbidity, such as lymph edema and urological complications [11]. For patients with lymph node metastases, chemoradiation is the treatment of choice since it reduces local and distant recurrences [12] Preoperative diagnostic modalities such as CT scan and MRI have a good specificity, but a low sensitivity [13,14]. This explains why a certain number of patients, in whom the diagnosis of positive LN is only made after pathological examination, still receive a combined treatment of surgery and pelvic irradiation
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