A first-in-human study of Brozopentyl Sodium, following single and multiple ascending intravenous infusion in Chinese healthy volunteers.

BACKGROUND: Brozopentyl Sodium (BZP), a novel agent for ischemic stroke, has shown promising results in preclinical pharmacological studies, prompting the initiation of the first-in-human investigation. PURPOSE: This study aimed to assess the safety, tolerability, and pharmacokinetic (PK) characteristics of BZP in Chinese healthy volunteers. METHODS: The study consisted of two parts. Part I was a single-center, randomized, single-blinded, placebo-controlled, single-ascending study with six BZP dose cohorts (SAD: 25, 50, 100, 200, 300, and 400 mg). Part II was a single-center, randomized, single-blinded, placebo-controlled, multi-dose- and dose-elevated study with three BZP dose cohorts (MAD: 50, 100, and 200 mg). Doses were administered once daily on days 1 and 7 and twice daily on days 2-6. The PK properties of BZP and its bioactive metabolites, BNBP, were assessed. Safety and tolerability evaluations were also conducted. RESULTS: In the SAD study, BZP reached peak plasma concentrations (Tmax) at the end of administration, with median Tmax values ranging from 1 to 1.03 h, while BNBP reached Tmax between 1.25 to 1.38 h. The terminal half-lives (T1/2) were approximately 8 h for BZP and 15 h for BNBP. In the MAD study, steady-state plasma concentrations of BZP were reached by day 5. There was minimal accumulation of both BZP and BNBP after 7 days of administration. The area under the plasma concentration-time curve from 0 to time of the last measurable concentration (AUC0-t) and maximum plasma drug concentration (Cmax) showed dose-proportional increases for BZP but not for BNBP in both study parts. Single and multiple doses of BZP demonstrated a good safety profile and were well-tolerated. CONCLUSION: BZP displayed safety, good tolerability and predictable PK characteristics following both single and multiple ascending intravenous administrations. These findings provide a basis for further clinical development of BZP for ischemic stroke patients.

A micro-peptide encoded by HOXB-AS3 promotes the proliferation and viability of oral squamous cell carcinoma cell lines by directly binding with IGF2BP2 to stabilize c-Myc.

HOXB-AS3 is a long non-coding RNA and recent studies have shown that the HOXB-AS3-encoded micro-peptide was associated with the progression of colon cancer tumorigenesis; however, the biofunction of HOXB-AS3 varies in different types of cancer and the potential function in oral squamous cell carcinoma (OSCC) is still unknown. The Cancer Genome Atlas (TCGA) database was searched and the expression patterns of HOXB-AS3 in head and neck carcinoma were analyzed. Reverse transcription-quantitative PCR and western blot analysis was used to measure the mRNA and protein expression level of HOXB-AS3 in patients with OSCC, respectively. Next, HOXB-AS3 was knocked down in 2 OSCC cell lines to investigate the biological function of the HOXB-AS3-encoded protein using a Cell Counting Kit-8 and colony formation assays. To further identify the potential mechanism of the HOXB-AS3-encoded protein, co-immunoprecipitation was also used to detect the interaction between HOXB-AS3 and IGF2BP2, while HOXB-AS3 was re-expressed to determine whether the HOXB-AS3-encoded protein and not HOXB-AS3 exerted its function in OSCC. HOXB-AS3 was upregulated in OSCC tissues, in both TCGA database and in patients with OSCC recruited into the present study. HOXB-AS3 was associated with poor prognosis in OSCC. The proliferation and viability decreased in the 2 OSCC cell lines following knock down of HOXB-AS3. HOXB-AS3 was also found to encode a protein that directly interacted with IGF2BP2 and thereby promoted the stability of c-myc. Taken together, the results from the present study indicated that increased HOXB-AS3 expression was associated with poor prognosis in OSCC. This indicated that HOXB-AS3 and its encoded protein promoted OSCC cell proliferation and viability by maintaining c-Myc mRNA stability by directly binding to IGF2BP2.

[Apical barrier technology to treat chronic apical periodontitis caused by type â ¡ dens invaginatus: a case report].

Dens invaginatusis a rare malformation of the teeth, resulting in frequent pulp necrosis and chronic apical periodontitis. In this paper, the apical barrier technology was used to treat a case of chronic apical periodontitis caused by type Ⅱ dens invaginatus.

Downregulation of LINC00515 in high-grade serous ovarian cancer and its relationship with platinum resistance.

Aim: To investigate the expression of long intergenic noncoding RNA 00515 (LINC00515) in high-grade serous ovarian cancer (HGSOC) and its potential correlation with platinum resistance. Patients & methods: Expression of LINC00515 in HGSOC (n = 115) and normal (n = 19) tissues was detected via quantitative real-time PCR (qRT-PCR). We further explored the statistical significance of the relationship between LINC00515 expression and platinum resistance in HGSOC. Results: LINC00515 was gradually downregulated in the order of normal > platinum-sensitive > platinum-resistant tissue (p < 0.05). Results demonstrated that LINC00515 downregulation was correlated with platinum resistance and relapse-free survival (RFS) of HGSOC (p < 0.05). Conclusion: LINC00515 downregulation is correlated with HGSOC development, platinum resistance and RFS, supporting its utility as a potential biomarker to predict platinum resistance and prognosis of RFS.

Simultaneous determination of six tyrosine kinase inhibitors in human plasma using HPLC-Q-Orbitrap mass spectrometry.

AIM: Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. MATERIALS & METHODS: An HPLC-Q-Orbitrap method (based on HPLC-MS/MS) was developed and validated for the simultaneous detection and quantitation of six tyrosine kinase inhibitors in human plasma. Sample was extracted by liquid-liquid extraction (ethyl acetate: tert-Butyl methyl ether, 1:1 v/v). The method shows a high level of accuracy and reproducibility. The lower limit of quantification was 0.02 ng/ml for apatinib, 0.1 ng/ml for crizotinib, 2.0 ng/ml for lapatinib and 0.05 ng/ml for erlotinib, gefitinib and icotinib. This method was successfully used for apatinib monitoring in plasma of patients with NSCLC. CONCLUSION: This simple and reproducible method has potential for monitoring of tyrosine kinase inhibitors in patients' plasma.

Modified filter-aided sample preparation (FASP) method increases peptide and protein identifications for shotgun proteomics.

RATIONALE: Mass spectrometry (MS)-based protein identification depends mainly on protein extraction and digestion. Although sodium dodecyl sulfate (SDS) can preclude enzymatic digestion and interfere with MS analysis, it is still the most widely used surfactant in these steps. To overcome these disadvantages, a SDS-compatible proteomic technique for SDS removal prior to MS-based analyses was developed, namely filter-aided sample preparation (FASP). METHODS: Herein, based on the effectiveness of sodium deoxycholate and a detergent removal spin column, we developed a modified FASP (mFASP) method and compared its overall performance, total number of peptides and proteins identified for shotgun proteomic experiments with that of the FASP method. RESULTS: Identification of 4570 ± 392 and 9139 ± 317 peptides and description of 862 ± 46 and 1377 ± 33 protein groups with two or more peptides from the ovarian cancer cell line A2780 was accomplished by FASP and mFASP methods, respectively. The mFASP method (21.2 ± 0.2%) had higher average peptide to protein coverage than FASP method (13.2 ± 0.5%). More hydrophobic peptides were identified by mFASP than by FASP, as indicated by the GRAVY score distribution. CONCLUSIONS: The reported method enables reliable and efficient identification of proteins and peptides in whole-cell extracts containing SDS. The new approach allows for higher throughput (the simultaneous identification of more proteins), a more comprehensive investigation of proteins, and potentially the discovery of new biomarkers. Copyright © 2016 John Wiley & Sons, Ltd.

The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer.

Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961, and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.

Differential microRNA expression by Solexa sequencing in the sera of ovarian cancer patients.

MicroRNAs are a class of small noncoding RNA which play important regulatory roles in a variety of cancers. MiRNA-specific expression profiles have been reported for several pathological conditions. In this study, we combined large scale parallel Solexa sequencing to identify 11 up-regulated miRNAs and 19 down-regulated miRNAs with computational techniques in the sera of ovarian cancer patients while using healthy serum as the control. Among the above, four miRNAs (miR-22, miR-93, miR-106b, miR-451) were validated by quantitative RT-PCR and found to be significantly aberrantly expressed in the serum of ovarian cancer patients (P<0.05). There were no significant differences between samples from cancer stage I/II and III/IV. However, the levels of miR-106b (p=0.003) and miR-451 (p=0.007) were significantly different in those patients under and over 51 yearsof age. MiR-451 and miR-93 were also specific when analyzed with reference to different levels of CA125. This study shows that Solexa sequencing provides a promising method for cancer-related miRNA profiling, and selectively expressed miRNAs could be used as potential serum-based biomarkers for ovarian cancer diagnosis.

[Effect of miRNA-106a expression on the prognosis of patients with esophageal squamous cell carcinoma].

OBJECTIVE: To study the expression of miRNA-106a gene in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features and prognosis of ESCC patients. METHODS: Real-time fluorescence quantitative polymerase chain reaction (PCR) assay was used to determine the expression of miRNA-106a gene in esophageal cancer tissue and corresponding normal mucosa of 81 cases. Immunohistochemical technique was applied to detect the expression of p53, human epidermal growth factor receptor 2 (HER-2), DNA topoisomerase II (Topo II) and multidrug resistance-associated protein (MRP). The association of miRNA-106a expression with clinicopathological features, expression of related proteins, and prognosis of the patients was analyzed. RESULTS: Among the 81 cases, under-expression of miRNA-106a gene was found in 48 cases (59.3%), normal expression in 22 cases (27.2%), and overexpression in 11 cases (13.6%). The expression of miRNA-106 gene was significantly associated with lymph node metastasis, pathological stage, and nerve invasion (all P < 0.05), significantly associated with expression of p53 (P = 0.006), and not significantly associated with expressions of HER-2, Topo II and MRP proteins (all P > 0.05). The expression of miRNA-106a gene was also significantly associated with progression-free survival (PFS, P = 0.032), but not significantly with overall survival (OS, P = 0.486). The results of Cox multivariate regression analysis showed that the PFS of ESCC patients was significantly correlated with lymph node metastasis (P = 0.029), but not correlated with the age, gender, tumor length, T stage, degree of differentiation, nerve invasion, and miRNA-106a expression (all P > 0.05). CONCLUSIONS: In esophageal squamous cell carcinomas, the miRNA-106a gene is under-expressed, with tumor suppressor function, and may be regarded as a biological marker to assess the prognosis in patients with esophageal squamous cell carcinoma.

Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer.

BACKGROUND AND AIM: miR-21, a putative tumor oncomiR, is a frequently overexpressed miRNA in a variety of tumors. Because it targets tumor-suppressor genes it has been linked to tumor progression. In this study we investigated the role of miR-21 in esophageal squamous cell carcinoma (ESCC), and its possible mechanism. METHODS: Expression of miR-21 was detected by stem-loop RT-PCR in tissue from 76 invasive ESCC at stage I-IV and in their corresponding para-cancerous histological normal tissues (PCHNT). Thirty endoscopic esophageal mucosal biopsy specimens from non-tumor patients were used as controls. Expression of PTEN in 76 paired ESCC and PCHNT was investigated by real-time RT-PCR and an immunohistochemical method, respectively. Paired tumor and PCHNT specimens of 20 ESCC cases were randomly selected for western blot analysis. The effect of miR-21 on PTEN expression was assessed in the ESCC cell line with an miR-21 inhibitor to reduce miR-21 expression. Furthermore, the roles of miR-21 in cell biology were analyzed by use of miR-21 inhibitor-transfected cells. RESULTS: Stem-loop RT-PCR revealed miR-21 was significantly overexpressed in ESCC tissues and cell lines. Overexpression of miR-21 correlated with tumor status, lymph node metastasis, and clinical stage. We demonstrated that knockdown of miR-21 significantly increased expression of PTEN protein. Consequent PTEN expression reduced cell proliferation, invasion, and migration. CONCLUSIONS: Our findings suggest that miR-21 could be a potential oncomiR, probably by regulation of PTEN, and a novel prognostic factor for ESCC patients.

[Methylation status of CDH1 gene in preoperative abdominal lavage of patients with gastric cancer and its clinical significance].

OBJECTIVE: To explore the association between the progression of gastric cancer and the aberrant methylation of CDH1 gene in preoperative abdominal lavage fluid. METHODS: Real-time methylation-specific polymerase chain reaction(qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from preoperative abdominal lavage fluid in 92 patients with gastric cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated. RESULTS: Among the 92 patients with gastric cancer, aberrant methylation of CDH1 gene was detected in 45(48.9%) patients, including total aberrant methylation in 12(13.0%) cases and partly aberrant methylation in 33(35.9%) cases. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, lymphovascular invasion, infiltration depth, lymph node metastasis, distant metastasis, and clinical staging(all P<0.05). However, there were no significant associations between CDH1 methylation status with gender, age, tumor location, or Helicobacter pylori infection(all P>0.05). The median progression-free survival was 20 months for CDH1 methylation group and 38 months for non-methylated group, and the difference was statistically significant(P<0.01). Cox model analysis revealed that CDH1 methylation status in preoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in patients with gastric cancer(P=0.000, RR=332.88, 95%CI:21.71-5105.07). CONCLUSIONS: The aberrant methylation of 5'-CpG of CDH1 gene promoter is common in gastric cancer. The examination of CDH1 methylation status of abdominal lavage should be considered in the progression of gastric cancer.

Detection and prognostic analysis of serum protein expression in esophageal squamous cell cancer.

OBJECTIVE: To assess differences in serum proteins in esophageal squamous cell carcinoma patients. METHODS: 144 esophageal squamous cell carcinoma patients and 50 healthy volunteers were included in this study, with surface-enhanced laser desorption-ionization time-of-flight mass spectrometry and weak cation exchange magnetic beads. Follow-up allowed the relations between serum proteins and prognosis to be analyzed. RESULTS: A total of 93 protein peaks were detected (molecular weight range: 1500-3000), 10 demonstrating statistically significant differences. There were no differences in protein peaks between 92 patients with a survival more than 2 years and 52 patients with survival less than 2 years. There were two significantly different protein peaks between 45 stage II patients with a survival more than 2 years and 14 stage II patients with survival less than 2 years. There was one significantly different protein peak between 22 stage III patients with a survival more than 2 years and 29 stage III patients with survival less than 2 years. CONCLUSION: Differences of serum proteins in esophageal squamous cell carcinoma are related to prognosis of patients. The protein fingerprint can be helpful for clinical diagnosis and treatment.

[Expression of a protein peak(3144 m/z) in serum and its clinical significance in patients with gastric cancer].

OBJECTIVE: To investigate the expression of protein peak (3144 m/z) in serum and of its association with clinical pathological characteristics and prognosis in patients with gastric cancer. METHODS: Three hundred and twenty seven pathologically confirmed gastric cancer patients were recruited from February 2006 to October 2008 in the Zhejiang Cancer Hospital. SELDI-TOF-MS was employed to detect the expression of protein peak (3144 m/z) in preoperative serum. RESULTS: The positive rate of 3144 m/z protein peak was 33.9% (111/327), significantly higher than that of CEA (21.1%,69/327), and the difference was statistically significant (P<0.01). The positive rate of combined detection of protein peak (3144 m/z)and CEA was 45.6% (149/327). The expression of protein peak (3144 m/z) was associated with clinical staging (P<0.01), nervous invasion (P<0.01), tumor size (P<0.01), vascular invasion (P<0.05), lymph node metastasis (P<0.05), expression of CEA (P<0.05), and depth of infiltration (P<0.05). Significant difference was observed in 3-year survival rate between the patients with protein peak and patients without protein peak (44.7% vs. 64.4%, P<0.01). However, 3144 m/z protein peak was not an independent prognostic factor on multivariate Cox regression analysis (P=0.057). CONCLUSION: Protein peak (3144 m/z) may be used as a diagnostic or prognostic marker of gastric cancer.

Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay.

AIM: Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers. METHODS: A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). RESULTS: Thirty eight specimens produced evaluable results (90.5%). The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity: cisplatin + paclitaxel was sensitive in 16 of 38 (42.1%) of samples, while nedaplatin+paclitaxel was more effective, which was sensitive in 20 of 38 cases (52.6%). CONCLUSION: There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients.

Primary study of lymph node metastasis-related serum biomarkers in breast cancer.

The aim of this study was to detect the pretreatment serum protein profiles of breast cancer patients by mass spectrometry (MS) to screen candidate tumor biomarkers, which will supply a simple, accurate, and minimally invasive method to predict the axillary lymph node metastasis of breast cancer. We used magnetic bead-based weak cation-exchange chromatography followed by matrix-assisted laser desorption and ionization time-of-flight MS to detect proteins in the sera of 54 cases of axillary node-negative breast cancer, 47 cases of axillary node-positive breast cancer, and 101 healthy controls. The protein profiles were analyzed to screen tumor biomarkers and lymph node metastasis-associated proteins to establish and verify a diagnostic model. Comparison of the protein profiles between the two cancer groups resulted in a total of 111 discriminate m/z peaks that were associated with breast cancer. Furthermore, 40 discriminate m/z peaks were detected between breast cancer patients with and without axillary node metastases. Four protein m/z peaks at 5,643, 4,651, 2,377, and 2,240 were used to construct a diagnosis model, and cross-validation indicated that breast cancer with and without axillary node metastasis was identified with 87.04% sensitivity (47/54), 87.23% specificity (41/47), and 87.13% accuracy (88/101). These proteins could potentially be used as predictive biomarkers to distinguish between breast cancer patients with or without lymph node metastasis.

Identification of serum protein markers for breast cancer relapse with SELDI-TOF MS.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to screen serum samples to identify protein markers for early breast cancer relapse. We collected 67 serum samples from patients with breast cancer (24 preoperative; 23 postoperative without breast cancer relapse; 20 postoperative with breast cancer relapse). Eight protein peaks varied between the presurgical group and the postsurgical group without breast cancer relapse; 4 protein peaks were differentially expressed between the postsurgical patients without relapse and patients with relapse. The peak at 3964 m/z dropped after surgery and rebounded after relapse (P < 0.01). These results indicate that there are differences in serum protein expression among the three different groups of patients. SELDI-TOF MS could be used to screen blood samples for the early detection of relapse in primary breast cancer patients. Specifically, protein peak at 3964 m/z is a potential biomarker for the detection of early breast cancer relapse.

Comprehensive profiling of the low molecular weight proteins and peptides in weak cation exchange beads human serum retentate.

Mass spectrometric profiling using ProteinChip and magnetic beads has rapidly grown over the past years, particularly to generate serum profiles for cancer diagnosis. The molecular weights of these distinguishing peaks are usually under 30 kDa. To identify those low molecular weight proteins and peptides is important for specific assays to be developed and increases biological insight. In this study, low molecular weight proteins and peptides from serum were purified by a combination of weak cation exchange magnetic beads and high performance liquid chromatography. The purified proteins and peptides were analyzed by 1D SDS PAGE, SELDI and LC-MS/MS. 246 proteins were identified from the HPLC fractions by LC-MS/MS. 95(38.62%) proteins were first identified in serum compare with Sys-BodyFluid database. 11(11/96) proteins were documented cancer associated proteins. We also observed about 109 proteins/peptides in SELDI mass spectrum, and 13 of the SELDI features were identified.

[Use of serum protein profiling for early diagnosis of gastric cancer].

OBJECTIVES: To identify serum biomarkers associated with early gastric cancer. METHODS: Serum proteins or peptides were purified with weak cation exchange magnetic beads in 433 patients with gastric cancer and 120 healthy subjects. Distinct peaks were selected using Biomarker Wizard software. The area under receiver operating characteristic curve(AUC) was generated to analyze discrimination capability of peaks between gastric cancers and health people. RESULTS: Thirteen distinct peaks were identified between 42 gastric cancer and 42 health people matched by age and gender(P<0.001). There were 5 peaks (2745, 2768, 6629, 3402, and 6436 m/z) with AUC greater than 0.8. Peak of 6629 m/z was identified to be transthyretin. The sensitivity and specificity of 6629 m/z were 65.5% and 92.0%. The sensitivity of 6629 m/z was 59.4% in I(A gastric cancer. CONCLUSION: Transthyretin precursor may be of value in the early diagnosis of gastric cancer.

[Clinical significance of serum proteomic profiling before and after cervical cancer surgery].

OBJECTIVE: To investigate the value of serum proteomic profiling in cervical cancer detected pre-surgery and post-surgery. METHODS: Magnetic bead and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect the serum samples from 54 cases with cervical cancer before and after surgery and 53 serum samples from healthy women. The results of spectra were analyzed by Biomarker Wizard software. RESULTS: Significant variation of proteomic profiling between pre-surgery and post-surgery were analyzed. There were 22 proteins with different mass/charge (M/Z) values significantly different (P < 0.01) at the M/Z value range from 1500 to 50 000, among of which relative content of proteins with M/Z 3981, 4290, and 28 066 in pre-surgery cervical cancer patients were higher than those in health women [(1.51 +/- 1.78)% vs (0.83 +/- 0.38)%, (2.70 +/- 2.19)% vs (1.72 +/- 0.91)%, (1.99 +/- 1.70)% vs (0.92 +/- 0.95)%; P < 0.01], while in the post-surgery patients, relative content of these three proteins significantly decreased to (0.59 +/- 0.45)%, (1.01 +/- 0.64)%, (0.54 +/- 0.37)%, respectively. But the relative content of another three proteins with M/Z 11 487, 11 529, and 11 678 were significantly increased in post-surgery patients [(0.38 +/- 1.41)% vs (2.74 +/- 3.67)%, (0.16 +/- 0.46)% vs (2.00 +/- 1.76)%, (1.02 +/- 1.67)% vs (7.71 +/- 9.46)%; P < 0.01]. CONCLUSION: Serum proteomic profiling could screen out the proteins which had significant variation between pre-surgery and post-surgery serum, of which with M/Z 3981, 4290, and 28 066 may be related with tumor burden, while with M/Z 11 487, 11 529, and 11 678 may be response to surgical stress.

[Application of SELDI-TOF serum proteome profiling in cervical squamous cell carcinoma].

BACKGROUND & OBJECTIVE: Up to now, there is no valid biomarker in early diagnosis of cervical cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a new technique used to identify biomarkers for cancers. This study was to screen new biomarkers and build diagnostic models for early diagnosis of cervical cancer by SELDI-TOF-MS. METHODS: SELDI-TOF-MS was used to detect the serum proteomic patterns of 91 patients with early stage cervical squamous cell carcinoma, 15 patients with cervical intraepithelial neoplasia III (CIN III), and 55 healthy women (control). The serum proteomic spectra were generated on weak cation exchange (WCX2) chips. Differences in protein peaks were analyzed using Biomarker Wizard software. The diagnostic model was built by Biomarker Patterns software and further valuated by a large-scale blind test. RESULTS: A total of 122 protein peaks were detected at the molecular range of 1.5 to 20 ku, among which 19 ones were significantly different between invasive cervical squamous cell carcinomas and controls (P<0.001). A diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z was established. Its specificity was 83.78% (31/37) and its sensitivity was 97.29% (36/37). A sensitivity of 94.44% (51/54) and a specificity of 94.44% (17/18) in a large-scale blind test were obtained. CONCLUSION: The diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z can discriminate cervical cancer patients from healthy women.