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Aim: This study evaluated the clinical value of the combined detection of serum cathepsin L (CL), heparanase (Hpa), and matrix metalloproteinase-9 (MMP-9) for determining the degree of ovarian cancer invasion and metastasis before surgery., Patients and Methods: Enzyme-linked immunosorbent assays were used to measure the serum content of CL, Hpa, and MMP-9 in 217 patients with untreated ovarian cancer before surgery, 100 patients with benign ovarian tumors, and 101 healthy women as controls. In addition, the degrees of invasion and metastasis were assessed by the 'gold standard' of clinicopathological diagnosis. The associations of the preoperative serum CL, Hpa, and MMP-9 levels with the clinicopathological factors and metastatic status were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the usefulness of these markers for determining the degree of ovarian cancer invasion before surgery., Results: The serum CL, Hpa, and MMP-9 levels were significantly higher (p=0.001) in patients with malignant ovarian cancer compared with patients with benign ovarian tumors and healthy controls. The serum CL level was significantly higher in patients with epithelial ovarian carcinoma compared with non-epithelial ovarian carcinoma (p=0.048), whereas the serum levels of Hpa (p=0.109) and MMP-9 (p=0.544) did not differ significantly between these two groups. The serum CL, Hpa, and MMP-9 levels correlated with the degree of differentiation and the FIGO staging (p>0.05). The serum CL (p=0.030) and MMP-9 (p=0.010) levels were significantly associated with peritoneal metastasis, and the serum Hpa level (p=0.042) was associated with distant metastasis. A ROC curve analysis revealed sensitivity of 60.9%, 69.6%, and 72.2%, and specificity of 57.4%, 67.2%, and 68.9% for the preoperative serum levels of CL, Hpa, and MMP-9, respectively, as tumor markers for the degree of extra-pelvic metastasis., Conclusion: Elevated serum CL, Hpa, and MMP-9 levels are correlated with malignant invasion and progression in ovarian cancer. The combined detection of serum CL, Hpa, and MMP-9 may be useful for determining the extent of ovarian cancer metastasis before surgery.

Objective: To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA(125) in detecting and monitoring ovarian cancer., Methods: Circulating IgG, IgM autoantibodies against ovarian cancer associated antigens which included TM4SF1, C1D, TIZ, OV-142, FXR1 and OV-189 were measured by indirect ELISA in serum from 126 patients with ovarian cancer (prior treatment), 42 patients with benign ovarian masses, 142 healthy women. Cut off value of IgG, IgM autoantibodies were determined by receive operating characteristic (ROC) curve. CA(125) was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum), combining autoantibody spectrum with CA(125) by binary logistic regresion. The positive ratio of autoantibody spectrum in serum (prior and post treatment) of 24 synchronization patients with ovarian cancer was analyzed to evaluate the value in monitoring state of illness., Results: Our data indicated that serum contains IgG, IgM autoantibodies against ovarian cancer associated antigens. The positive ratio of IgG autoantibodies in serum from ovarian cancer patients and cancer-free patients were 34.1% - 47.6% and 13.0% - 19.0%, respectively (P < 0.05). The positive ratio of IgM autoantibodies in serum from ovarian cancer patients and cancer-free patients were 39.7% - 53.2% and 12.0% - 33.2%, respectively (P < 0.05). The positive ratio of IgG autoantibodies against FXR1 and IgM autoantibodies against TIZ, FXR1 and OV-189 in early stage (I-II) ovarian cancer (55.3%, 63.8%, 61.7% and 66.0%) were significantly higher than those in advanced (III-IV) ovarian cancer (34.2%, 39.2%, 26.6%, 45.6%; all P < 0.05). Combining five autoantibodies (TM4SF1 IgG, TM4SF1 IgM, C1D IgG, FXR1 IgG and TIZ IgM) showed significantly improved sensitivity (75.4%, P < 0.05), lower specificity (78.3%, P < 0.05) and similar accuracy (77.1%, P > 0.05) in detecting ovarian cancer compared to those of CA(125) (61.1%, 88.0%, 77.1%). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76.6%), compared to those of CA(125) (51.1%, P < 0.05). Combining autoantibody spectrum with CA(125) showed significantly improved sensitivity (85.7%), specificity (90.8%)and accuracy (88.7%) in detecting ovarian cancer compared to those of autoantibody spectrum alone (all P < 0.05), while CA(125) (61.1%, P < 0.05; 88.0%, P > 0.05; 77.1%, P < 0.05). The positive ratio of combine the autoantibody spectrum with CA(125) was significantly lower in 24 post-treatment serum (42%) compared to the pairing prior treatment serum (88%, P < 0.05)., Conclusion: Combining the autoantibody spectrum against ovarian cancer associated antigens with CA(125) can improve sensitivity, specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.

Objective: To explore the relationship between hormone therapy (HT) in women with ovarian malignancy and prognosis., Methods: HT was used in 31 patients with ovarian cancer after surgery, and 44 cases with ovarian cancer served as control. The expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PR) was detected by immunohistochemical staining respectively. The level of serum calcitonin and transforming growth factor alpha (TGFalpha) was detected by radio-immune and enzyme-linked immunosorbent assay pre- or post-surgery, as well as half a year to one year later post-surgery respectively in these cases. The survival curve of Kaplan-Meier and log-rank test as well as scale risk of Cox model were used to analyze the relationship between HT and prognosis of ovarian cancer., Results: (1) The results of log-rank test showed that there was no difference in survival curve of patients with or without HT [(1108 +/- 52), (1086 +/- 43) d; P = 0.940]; the results of scale risk of Cox model also showed that HT was not an independent prognosis factor for patients with HT. (2) There was no relationship with HT and the accumulated survival in patients with either positive or negative expression of ERalpha, ERbeta and PR in tissue; as well as between HT and the level of serum TGFalpha pre-, post-surgery, or half a year to one year after surgery. (3) The level of serum calcitonin in patients without HT post-surgery half a year to one year later was higher than that pre-surgery [(141 +/- 13), (95 +/- 11) microg/L; P < 0.05], but there was no significant difference between patients with HT half a year to one year later post-surgery and pre-surgery [(90 +/- 18) microg/L, (93 +/- 14) microg/L; P > 0.05]. (4) There was a significant difference in body and emotion function between HT and without HT groups [(1.84 +/- 1.50), (1.45 +/- 0.82); (12.69 +/- 10.20), (12.90 +/- 11.61); P < 0.05], as well as in sex quality and autonomic nerve maladjustment and in the special list made [(1.05 +/- 0.74), (1.77 +/- 1.08); (10.10 +/- 3.21), (13.09 +/- 4.30); P < 0.05]., Conclusions: There is no adverse influence on prognosis in using of HT for patients with ovarian cancer after surgery. HT for patients with ovarian cancer post-surgery can help keep a stable level of serum calcitonin as well as improve the quality of life.

Objective: To investigate the value of autoantibody of breast cancer susceptibility 1-associated RING domain (BARD1) splice variant (OV-142) in detection of ovarian cancer., Methods: We cloned OV-142 gene into plasmid pET-30b(+). The recombinant protein of OV-142 was expressed in pET-30b(+) system and purified. The autoantibody of OV-142 was detected by indirect enzyme-linked immunosorbent assay (ELISA)., Results: We successfully constructed the recombinant plasmid of OV-142. The recombinant protein was expressed in pET-30b(+) system and purified. The purification rate of the recombinant protein was up to 90%. The relative amount of autoantibody of OV-142 detected by indirect ELISA was analyzed by receiver operating characteristic curve (ROC) and the cutoff value was determined. Combination of the autoantibody IgG of OV-142 and CA(125) was analyzed by logistic regression. The sensitivity, specificity and accuracy was 71.4%, 89.1%, and 81.9%, respectively, which were higher than IgG (41.3%, 84.2%, 66.8%) and CA(125) (61.1%, 88.0%, 77.1%) when used alone each., Conclusions: OV-142 is a splice variant of BARD1. It may be a potential immunotherapy target of ovarian cancer. Detection of autoantibody of OV-142 is a potent complementary tool of CA(125) in ovarian cancer diagnosis.

Objective: To explore epithelial ovarian cancer (EOC) antigens that are potentially useful for cancer early detection and therapy., Methods: A high quality cDNA library derived from ascites tumor cells of EOC patients (3 cases of serous EOC, 1 case of mucinous EOC, and 1 case of endometrial carcinoma of ovary) was constructed, and the method of combining serological analysis of recombinant cDNA expression libraries (SEREX) and suppression subtractive hybridization (SSH) was used for screening cDNA library. All of the positive clones were sequenced and bioinformatics analysis with BLAST software in GenBank was performed. Serological mini-arrays of recombinant tumor antigens (SMARTA) was used to investigate the prevalence of autoantibodies to these antigens in both 96 ovarian cancer patients and 96 cancer-free controls., Results: Fifty-five positive clones encoding different antigenic genes of EOC recognized by IgG and (or) IgM were obtained. It showed that these 55 clones derived from 45 distinct genes and these genes could be grouped into 6 classes as following according to homology with known expressed sequence tag (EST): (1) known ovarian carcinoma related genes: BARD1, et al; (2) homologous genes with other tumors: TM4SF1, et al; (3) homologous genes with special tissues: ILF3, FXR1, et al; (4) homologous genes with special function: TIZ, C1D, et al; (5) embryo originating genes: PKHD1, et al; (6) novel genes: OV-189, et al. SMARTA results showed that the positive ratio of five EOC antigens TM4SF1 (28% vs. 9%), C1D (21% vs. 6%), BARD1 (23% vs. 5%), FXR1 (23% vs. 8%), OV-189 (31% vs. 13%) which reacting with their IgG autoantibodies, three antigens TIZ (26% vs. 8%), FXR1 (28% vs. 11%), and OV-189 (18% vs. 7%) which reacting with their IgM autoantibodies in patients was higher than in controls (P < 0.05). The positive ratio of EOC antigens FXR1 (34% vs. 16%), and OV-189 (46% vs. 23%) reacting with their IgG autoantibodies and TIZ (40% vs. 18%), FXR1 (46% vs. 18%) which reacting with their IgM autoantibodies in stage I-II patients was higher than that in stage III-IV (P < 0.05). The positive ratio of OV-189 (67% vs. 26%) which reacting with its IgG autoantibodies in well differentiated cases was higher than in moderately-poorly differentiated cases (P < 0.01). Combination of the above antigens showed a 66% sensitivity and 73% accuracy in discriminating EOC. Combination of the autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 with CA125 showed an 83% sensitivity and 80% accuracy in discriminating EOC., Conclusions: The strategy of combination of SEREX and SSH is a potent tool in isolating tumor-associated antigen genes. Autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 are potential tumor markers in EOC detection.