| Neoadjuvant chemotherapy, namely preoperative chemotherapy, induced chemotherapy, initial chemotherapy or primary chemotherapy, has gained wide acceptance for treating patients with locally advanced breast cancer. In these patients the most acknowledged benefit is the reduction in tumor size allowing either a complete resection of an otherwise unresectable tumor or breast conservation surgery in some patients with large tumors. Although many patients benefit from chemotherapy, some fail to respond. However, the success of neoadjuvant chemotherapy in any given individual cannot be predicted. The uncertain benefit for a particular individual, as well as significant toxicity of chemotherapy in all patients, calls for development of methods to select the right patients for treatment and spare those who will not benefit. Meanwhile the application of neoadjuvant chemotherapy can downstage some patients’ axillary lymph node (ALN) status, so people want to find more accurate, and less invasive means of predicting ALN metastasis. A novel technology, surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) carved out such a new path to proteomics research on breast cancer. It can directly obtain high-throughput protein profilings from clinical samples with high sensitivity. The application of SELDI-TOF-MS has been reported to be capable of being used to diagnose malignancies of various organs, including the ovary, prostate, and pancreas. But the studys of proteomics to predict or monitor tumor response to chemotherapy are still very rare.Our current study was specifically designed to compare SELDI mass spectra of serum from chemotherapy responsive and non-responsive breast patients receiving the neoadjuvant treatment for identification the protein biomarkers which could predict or monitor tumor response to chemotherapy. We also hypothesized that proteomic alteration in the serum from breast cancer patients could predict ALN metastasis which could be caught by SELDI.Part 1The application of SELDI-TOF-MS in the prediction of tumor response to neoadjuvant chemotherapy in breast cancer patientsSELDI-TOF-MS protein chips were used to detect the serum proteomic patterns of 19 cases of chemotherapy responsive patients and 15 cases of chemotherapy non-responsive patients. Six potential biomarkers were found (5869 m/z,3291 m/z, 5894 m/z,9296 m/z.5953 m/z and 2220 m/z). The protein peaks of 5869 m/z.3291 m/z, 5894 m/z,9296 m/z and 5953 m/z were higher in the chemotherapy responsive patients while the protein peak of 2220 m/z was higher in the chemotherapy non-responsive patients. The prediction model was quite accurate with an accuracy of 82.4%.After neoadjuvant chemotherapy,25 patients got tumor shrinked while 9 patients’ tumor enlarged. With the method of SELDI-TOF-MS-5 protein peak were identified (3323 m/z,5869 m/z,5894 m/z,7775 m/z and 6470 m/z). The protein peaks of 3323 m/z,5869 m/z,5894 m/z and 7775 m/z were higher in the tumor shrinked patients while the protein peak of 6470 m/z was higher in the tumor enlarged patients. This model has an accuracy of 91.2%.As the two models both included the protein peaks of 5869 m/z and 5894 m/z, we think they may be potential biomarkers that can predict tumor response to neoadjuvant chemotherapy.Part 2The application of SELDI-TOF-MS in the monitoring of tumor response to neoadjuvant chemotherapy in breast cancer patientsWe first compared the protein fingerprints of the total 34 cases patients pre-chemotherapy and post-chemotherapy. Eleven discrepant proteins were screened which changed differently between the two groups. Then we checked these proteins in every 25 patients after every period of chemotherapy. The average value of proteins of last 3 periods was compared to the value of the first time in every patient in order to judge the protein peak was rise or drop after receiving chemotherapy. At last we found that the protein peak of 4302 m/z was drop in 76.9% patients of responsive group and rise in 66.7% patients of non-responsive group. So was the protein peak of 4645 m/z. The protein peak of 3291 m/z was drop in 61.5% patients of responsive group and rise in 66.7% patients of non-responsive group, and the protein peak of 5894 m/z was drop in 61.5% patients of responsive group and rise in 75% patients of non-responsive group. We think these 4 protein peaks may serve as biomarkers for monitoring tumor response to chemotherapy.Part 3The application of SELDI-TOF-MS in the ALN staging in breast cancer patientsSELDI-TOF-MS protein chips were used to detect the serum proteomic patterns of 18 cases of patients with ALN metastasis and 16 cases of patients without ALN metastasis. Five potential biomarkers were found (3164 m/z,3979m/z,9196 m/z,2734 m/z and 3963 m/z). The protein peaks of 3164 m/z,3979 m/z and 3963 m/z were higher in the patients with ALN metastasis while the protein peak of 9196 m/z and 2734 m/z were higher in the patients without ALN metastasis. This model has an accuracy of 88.2%.We also find the expression level of the protein peak of 3979 m/z was relevant to the number of metastatic lymph nodes. After searching for the protein database, we know that the protein peak of 3979 m/z maybe the substance P which is deserved for further studies. Conclusions1、The model composed by 5869 m/z,3291 m/z,5894 m/z,9296 m/z,5953 m/z and 2220 m/z could do the best in the division of chemotherapy responsive patients and chemotherapy non-responsive patients. The accuracy was 82.4%.2、The model composed by 3323 m/z,5869 m/z,5894 m/z,7775 m/z and 6470 m/z could do the best in the division of the tumor shrinked patients and the tumor enlarged patients. The accuracy was 91.2%.3、The protein peaks of 5869 m/z and 5894 m/z may be potential biomarkers that can predict tumor response to neoadjuvant chemotherapy.4、The 4 protein peaks (4302 m/z,4645 m/z,3291 m/z and 5894 m/z) may serve as biomarkers for monitoring tumor response to chemotherapy.5、The protein peak of 5894 m/z serves both as predictor and monitor for tumor response to chemotherapy, and it is deserved for further studies.6、The model composed by 3164 m/z,3979m/z,9196 m/z,2734 m/z and 3963 m/z could do the best in the division of patients with ALN metastasis and patients without ALN metastasis. The accuracy was 88.2%.7、The expression level of the protein peak of 3979 m/z was relevant to the number of metastatic lymph nodes. |
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