1.The expression of clock gene CLOCK and its clinical significance in nasopharyngeal carcinoma
Xiaomei LI ; Yuanyuan LI ; Chaofen ZHAO ; Lina LIU ; Qianyong HE ; Jieqing JIANG ; Yue CHEN ; Minghui YANG ; Yaxue TANG ; Yuxin LI ; Feng JIN
Chinese Journal of Oncology 2021;43(12):1255-1263
Objective:To explore the relationship between expression levels of CLOCK mRNA and protein and the clinical characteristics of patients with nasopharyngeal carcinoma.Methods:The frozen tissue specimens from 33 patients with nasopharyngeal carcinoma in the Affiliated Tumor Hospital of Guizhou Medical University from 2018 to 2019 were collected. Seventeen cases of tissue specimens from patients with nasopharyngeal chronic inflammation in the Affiliated Hospital of Guizhou Medical University in 2019 were collected. From 2008 to 2014, 68 cases of formalin-fixed paraffin-embedding (FFPE) nasopharyngeal carcinoma tissue and 37 cases of FFPE nasopharyngeal chronic inflammation tissue were collected from the Affiliated Tumor Hospital of Guizhou Medical University. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to detect the mRNA and protein expression levels of CLOCK. The nasopharyngeal carcinoma cells including CNE1, CNE2, 5-8F and the normal nasopharyngeal epithelial cell NP69 were cultured. qRT-PCR was used to detect the expression level of CLOCK mRNA in each cell line at the time points of ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22. The cosine method was used to fit the rhythm of CLOCK gene in nasopharyngeal carcinoma. The protein expression of CLOCK protein was detected by using immunohistochemical method in 68 cases of nasopharyngeal carcinoma and 37 cases of nasopharyngeal chronic inflammation tissue. Survival was analyzed by Kaplan-Meier method and Log rank test, and the influencing factors was analyzed by Cox regression model.Results:The expression levels of CLOCK mRNA in CNE1, CNE2 and 5-8F cells (0.63±0.07, 0.91±0.02 and 0.33±0.04, respectively) were lower than that in NP69 cell (1.00±0.00, P<0.05). The expression levels of CLOCK protein in CNE1, CNE2 and 5-8F cells (0.79±0.06, 0.57±0.05 and 0.74±0.10, respectively) were lower than that of NP69 cells (1.00±0.00, P<0.05). The expressions of CLOCK mRNA in nasopharyngeal carcinoma cells including CEN1, CNE2, 5-8F and normal nasopharyngeal epithelial cell NP69 were different at different time points, with temporal fluctuations. The fluctuation periods of CLOCK mRNA in CNE1, CNE2, 5-8F, and NP69 cells were 16, 14, 22 and 24 hours, respectively. The peak and trough times were ZT10: 40 and ZT18: 40, ZT10 and ZT3, ZT14: 30 and ZT3: 30, ZT12: 39 and ZT0: 39, respectively. CLOCK mRNA and protein expression levels in nasopharyngeal carcinoma tissues (0.37±0.20 and 0.20±0.26, respectively) were lower than those in nasopharyngeal chronic inflammation tissues (1.00±0.00 and 0.51±0.41, respectively, P<0.05). The 1, 3, and 5-year survival rates of patients in the CLOCK protein high expression group (CLOCK protein expression level ≥ 0.178) were 96.2%, 92.1%, and 80.1%, respectively, which were higher than those in the low expression group (CLOCK protein expression level <0.178, 92.9% , 78.6% and 57.1%, respectively, P=0.009). The 1, 3, and 5-year progression-free survival (PFS) rates of patients in the CLOCK protein high expression group were 96.2%, 87.8%, and 87.7%, respectively, which were higher than those in the low expression group (92.7%, 82.2%, and 70.8%, respectively, P=0.105). Compared with the low-expression group (100.0%, 96.9%, and 90.0%, respectively), the 1, 3, and 5-year recurrence-free survival rates of patients in the CLOCK protein high expression group (100.0%, 95.7%, and 95.7%, respectively) were not statistically significant ( P=0.514). Compared with the low-expression group (92.7%, 82.2%, and 79.3%), the 1, 3, and 5-year survival rates without metastasis in the CLOCK protein high expression group (96.2%, 92.0%, and 92.0%, respectively) were not statistically significant ( P=0.136). CLOCK protein expression and T stage were independent prognostic factors of overall survival ( P<0.05). Conclusions:The expression of CLCOK is downregulated in the nasopharyngeal carcinoma cell and nasopharyngeal carcinoma tissues. Clock gene CLOCK is rhythmically expressed in the nasopharyngeal carcinoma cells and normal nasopharyngeal epithelial cells. Compared with normal nasopharyngeal epithelial cells, the fluctuation period of CLOCK in nasopharyngeal carcinoma cells is shortened. The overall survival of patients in the CLOCK protein high expression group is better than that of low expression group. The expression of CLOCK protein is an independent influencing factor for overall survival. CLOCK gene may be a potential tumor suppressor gene in the nasopharyngeal carcinoma.
2.The expression of clock gene CLOCK and its clinical significance in nasopharyngeal carcinoma
Xiaomei LI ; Yuanyuan LI ; Chaofen ZHAO ; Lina LIU ; Qianyong HE ; Jieqing JIANG ; Yue CHEN ; Minghui YANG ; Yaxue TANG ; Yuxin LI ; Feng JIN
Chinese Journal of Oncology 2021;43(12):1255-1263
Objective:To explore the relationship between expression levels of CLOCK mRNA and protein and the clinical characteristics of patients with nasopharyngeal carcinoma.Methods:The frozen tissue specimens from 33 patients with nasopharyngeal carcinoma in the Affiliated Tumor Hospital of Guizhou Medical University from 2018 to 2019 were collected. Seventeen cases of tissue specimens from patients with nasopharyngeal chronic inflammation in the Affiliated Hospital of Guizhou Medical University in 2019 were collected. From 2008 to 2014, 68 cases of formalin-fixed paraffin-embedding (FFPE) nasopharyngeal carcinoma tissue and 37 cases of FFPE nasopharyngeal chronic inflammation tissue were collected from the Affiliated Tumor Hospital of Guizhou Medical University. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to detect the mRNA and protein expression levels of CLOCK. The nasopharyngeal carcinoma cells including CNE1, CNE2, 5-8F and the normal nasopharyngeal epithelial cell NP69 were cultured. qRT-PCR was used to detect the expression level of CLOCK mRNA in each cell line at the time points of ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22. The cosine method was used to fit the rhythm of CLOCK gene in nasopharyngeal carcinoma. The protein expression of CLOCK protein was detected by using immunohistochemical method in 68 cases of nasopharyngeal carcinoma and 37 cases of nasopharyngeal chronic inflammation tissue. Survival was analyzed by Kaplan-Meier method and Log rank test, and the influencing factors was analyzed by Cox regression model.Results:The expression levels of CLOCK mRNA in CNE1, CNE2 and 5-8F cells (0.63±0.07, 0.91±0.02 and 0.33±0.04, respectively) were lower than that in NP69 cell (1.00±0.00, P<0.05). The expression levels of CLOCK protein in CNE1, CNE2 and 5-8F cells (0.79±0.06, 0.57±0.05 and 0.74±0.10, respectively) were lower than that of NP69 cells (1.00±0.00, P<0.05). The expressions of CLOCK mRNA in nasopharyngeal carcinoma cells including CEN1, CNE2, 5-8F and normal nasopharyngeal epithelial cell NP69 were different at different time points, with temporal fluctuations. The fluctuation periods of CLOCK mRNA in CNE1, CNE2, 5-8F, and NP69 cells were 16, 14, 22 and 24 hours, respectively. The peak and trough times were ZT10: 40 and ZT18: 40, ZT10 and ZT3, ZT14: 30 and ZT3: 30, ZT12: 39 and ZT0: 39, respectively. CLOCK mRNA and protein expression levels in nasopharyngeal carcinoma tissues (0.37±0.20 and 0.20±0.26, respectively) were lower than those in nasopharyngeal chronic inflammation tissues (1.00±0.00 and 0.51±0.41, respectively, P<0.05). The 1, 3, and 5-year survival rates of patients in the CLOCK protein high expression group (CLOCK protein expression level ≥ 0.178) were 96.2%, 92.1%, and 80.1%, respectively, which were higher than those in the low expression group (CLOCK protein expression level <0.178, 92.9% , 78.6% and 57.1%, respectively, P=0.009). The 1, 3, and 5-year progression-free survival (PFS) rates of patients in the CLOCK protein high expression group were 96.2%, 87.8%, and 87.7%, respectively, which were higher than those in the low expression group (92.7%, 82.2%, and 70.8%, respectively, P=0.105). Compared with the low-expression group (100.0%, 96.9%, and 90.0%, respectively), the 1, 3, and 5-year recurrence-free survival rates of patients in the CLOCK protein high expression group (100.0%, 95.7%, and 95.7%, respectively) were not statistically significant ( P=0.514). Compared with the low-expression group (92.7%, 82.2%, and 79.3%), the 1, 3, and 5-year survival rates without metastasis in the CLOCK protein high expression group (96.2%, 92.0%, and 92.0%, respectively) were not statistically significant ( P=0.136). CLOCK protein expression and T stage were independent prognostic factors of overall survival ( P<0.05). Conclusions:The expression of CLCOK is downregulated in the nasopharyngeal carcinoma cell and nasopharyngeal carcinoma tissues. Clock gene CLOCK is rhythmically expressed in the nasopharyngeal carcinoma cells and normal nasopharyngeal epithelial cells. Compared with normal nasopharyngeal epithelial cells, the fluctuation period of CLOCK in nasopharyngeal carcinoma cells is shortened. The overall survival of patients in the CLOCK protein high expression group is better than that of low expression group. The expression of CLOCK protein is an independent influencing factor for overall survival. CLOCK gene may be a potential tumor suppressor gene in the nasopharyngeal carcinoma.
3.Optimal ratio of tip projection to nasal length for Chinese: a four-year clinical study
Chen ZHANG ; Jieqing WANG ; Chunying GE ; Wei YANG ; Liang CHEN ; Xiaoli JIANG
Chinese Journal of Medical Aesthetics and Cosmetology 2020;26(5):381-384
Objective:To find out the optimal ratio of tip projection to nasal length for Chinese in order to help doctors to reduce the dissatisfactory rate of rhinoplasty.Methods:The authors retrospectively reviewed the records of patients with rhinoplasty from June 2015 to June 2018. The patients were classified into satisfactory, underprojected and overprojected groups. The average, maximum, minimum of tip projection (TP), nasal length (NL) and TP/NL, median of TP/NL of each group were measured. The results were used in later patients to assess their efficacy by comparing the dissatisfactory rates of patients before and after June 2018.Results:In satisfactory group, the mean of TP/NL was 0.63 with minimum 0.56, maximum 0.69, and median 0.64 in primary cases, while the mean of TP/NL was 0.63 with minimum 0.52, maximum 0.75, and median 0.64 in secondary cases. In underprojected group, the mean of TP/NL was 0.60 with median 0.58. In overprojected group, the mean of TP/NL was 0.64 with median 0.65. The dissatisfactory rates of patients before and after June 2018 were 8% and 2.2%, respectively ( P>0.05). Conclusions:The optimal ratio of tip projection to nasal length for Chinese is near 0.63-0.64. Combined with the desire of patient, it is possible for doctors to satisfy the patients by controlling tip projections between 2.5 cm to 2.8 cm.
4.Correlation between Change of Routine Blood Parameters and Prognosis of SSHL Patients
Silin ZHANG ; Wensheng ZHOU ; Fangling HU ; Hongxing LIANG ; Hongqun JIANG ; Jieqing YU
Journal of Audiology and Speech Pathology 2018;26(1):21-24
Objective To investigate the correlation between the mean platelet volume (MPV) ,neutrophil-to -lymphocyte(NLR) and the severity as well as prognosis of sudden sensorineural hearing loss (SSHL) patients . Methods A retrospective cohort study involved 172 patients with SSHL from January 2012 to May 2015 .The distri-bution characteristics of routine blood (white blood cells ,neutrophil ,lymphocyte ,MPV ,NLR) in different audio-metric curves (hearing loss at low frequencies ,flat type ,high frequencies ,and total deafness) and prognosis of re-covery (complete ,partial ,slight ,and no recovery )were analyzed by SPSS 19 .0 analysis chi square test ,and the prognosis was estimated by using the receiver operating characteristic curve (ROC) .Results MPV and NLR levels in the severe and profound hearing loss group were significantly higher than that in different audiometric curves (P<0 .01 and P<0 .01) .MPV and NLR level in the partial recovery group and the no recovery group were signifi-cantly higher than that in the complete recovery group (P<0 .01 and P<0 .01) .The value of the MPV and NLR showed negative correlation with the prognosis (hearing recovery ) ,and the lymphocyte was positive with the prog-nosis .The sensitivity and specificity of MPV and NLR count 24 hours after admission predicting the prognosis of hearing recovery were 66 .2% and 85 .5% ,58 .4% and 86 .7% ,respectively .Conclusion The changes of MPV and NLR in SSHL patients are related to the severity of hearing loss ,and NLR count at 24 hours after admission may play an important role in prognosis of this disease .
5. Comparison of the short-term and long-term outcomes of laparoscopic surgery and open surgery for early-stage cervical cancer
Hongying HE ; Zhijun YANG ; Dingyuan ZENG ; Desheng YAO ; Jiangtao FAN ; Renfeng ZHAO ; Jieqing ZHANG ; Xiaoxia HU ; Zhong LIN ; Yanming JIANG ; Li LI
Chinese Journal of Oncology 2017;39(6):458-466
Objective:
To evaluate the short-term and long-term outcomes after laparoscopic surgery compared with traditional laparotomy in cases of stage ⅠA2-ⅡA2 cervical cancer.
Methods:
We conducted a retrospective study on the clinical data of 1 863 patients diagnosed as FIGO stages ⅠA2-ⅡA2 cervical cancer in 6 third-grade class-A hospitals in Guangxi province between January 2007 and May 2014. One thousand and seventy-one received laparoscopy, and 792 received laparotomy.
6.Changes of circulating endothelial progenitor cells and their clinical significance in patients with acute cerebral infarction
Ru GONG ; Jieqing WAN ; Yiling FAN ; Jiyao JIANG
Chinese Journal of Trauma 2014;30(7):725-729
Objective To investigate the changes of circulating endothelial progenitor cells (EPCs) in patients with acute cerebral infarction or chronic cerebral ischemia and discuss the related clinical significance.Methods Circulating EPCs were isolated using staining markers of CD34,CD133,and kinase insert domain receptor (KDR).Peripheral venous blood was collected from patients with acute cerebral infarction within 24 hours of onset (infarction group,n =30),with chronic cerebral ischemia (ischemia group,n =20),and without cerebral ischemia (control group,n =10) to quantify circulating level of EPCs using flow cytometry and measure parameters of systolic pressure,glycosylated hemoglobin (HbAlc),total cholesterol (TC),and triglyceride (TG),and low density lipoprotein-cholesterol (LDL-C),and high density lipoprotein-cholesterol (HDL-C).Results CD34-,CD34/CD133-,and CD34/KDR-positive cells counted (14.2 ± 8.1)‰,(7.1 ± 4.1)‰ and (5.0 ± 3.7)‰ in infarction group,(28.5 ± 9.9)‰,(15.2 ± 3.7)‰ and (6.8 ± 2.0)‰ in ischemia group,and (44.8 ± 9.5) ‰,(22.1 ± 6.6) ‰ and (16.7 ± 6.9) ‰ in control group.Taken together,circulating level of EPCs lowered substantially in infarction and ischemia groups compared to control group (P < 0.05) and a far lower level was observed in infarction group (P < 0.05).Circulating level of EPCs in infarction group was in a moderate negative correlation with systolic pressure,TC,TG,and LDL-C (P < 0.05).Conclusions Decreased circulating level of EPCs may be a risk factor to the development of cerebral ischemia in acute cerebral infarction patients.Therefore,level of EPCs is vital for prediction,prevention and treatment of acute cerebral infarction.
7.Efficacy analysis of endovascular stenting for aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy
Xiaoming YIN ; Jieqing WAN ; Yiling FAN ; Yaohua PAN ; Shenghao DING ; Lei CHEN ; Jiyao JIANG
Chinese Journal of Cerebrovascular Diseases 2014;(4):196-200
Objective To investigate the efficacy of endovascular stenting for aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy. Methods The clinical data of 8 patients with symptomatic severe aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy were analyzed retrospectively. The patients were all received endovascular stenting,and their improvement of cerebral ischemic symptoms was observed. They were followed up by cervical color Doppler ultrasound.Results The whole brain vascular DSA confirmed that there were 24 severe arterial stenoses on the aortic arch arteries of extracranial segments in 8 patients,including 11 in internal carotid artery,2 in common carotid artery,10 in vertebral artery and 1 in subclavian artery. The patients were treated with vascular angioplasty and stenting respectively. All the patients were followed up for 1 year;there were no recurrence of cerebral ischemic symptoms.Cervical color Doppler ultrasound did not reveal any obvious restenosis. Conclusion Endovascular stent angioplasty for the treatment of aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy is relatively safe and feasible.
8.Estradiol activates MAPK signaling pathway by estrogen induced VEGF and bFGF in endometrial cancer cells
Yanqiong LU ; Si JIANG ; Jieqing ZHANG ; Honglin SONG ; Li LI
Chinese Journal of Obstetrics and Gynecology 2014;49(12):925-931
Objective To explore the effects of mitogen-activated protein kinase (MAPK) pathway by estradiol induced vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial cancer Ishikawa cells.Methods The experiments were divided into 4 groups:E2 group (Ishikawa cells treated with 1 p mol/L estradiol for 30 minutes); inhibitor group:including Ishikawa cells treated with 10 μmol/L Bibf1 120 (Bibf1 120 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib group),or treated with 10 p mol/L U0126 (U0126 group) for 60 minutes; inhibitor + E2 group:including Ishikawa cells treated with 10 μmol/L Bibf1120 (Bibf1120 + E2 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib + E2 group),or treated with 10 μmol/L U0126 (U0126+ E2 group) for 60 minutes following incubation with 1 μmol/L estradiol for 30 minutes; control group:only adding the culture medium without serum DMEM.(1) Western blot analysis was used to detect phosphorylation extracellular signal-regulated kinase 1/2(p-ERK 1/2) protein expression with stimulation in different concentrations of estradiol (0.01,0.1,1,10,100 μmol/L).(2) Quantitative fluorescent reverse transcription (qRT)-PCR and western blot analysis was used to test the level of mRNA and protein of VEGF,bFGF,MAPK kinase 1/2 (MEK1/2),extracellular signal-regulated kinase 1/2 (ERK1/2),p-ERK1/2 and phosphorylation MEK1/2 (p-MEK1/2).Flow cytometry were used to examine the cell cycle,and transwell chamber assay were used to detect the cell migration in different groups.Results The expression of the p-ERK1/2 protein at 0.01,0.1,1,10,100 μ mol/L were 0.16±0.03,0.10±0.03,0.41 ±0.04,0.19±0.03,0.19±0.03,there were significantly higher than that in control group(0.05±0.00,P<0.05),and which was more obvious at the concentration of 1 μmol/L estradiol.The expression level of VEGF,bFGF mRNA and protein in E2 group were higher than those in the control group (P<O.05).VEGF mRNA and protein in Bibf1120+E2 group were higher than those in E2 group.The expression of MEK1/2,ERK1/2 mRNA protein in E2 group were higher than those in control group (P<0.05).The expression of MEK1/2,ERK1/2 mRNA or p-MEK1/2,p-ERK1/2 protein in Bibf1120 + E2 group,Ponatinib+E2 group or U0126+E2 group were lower than those in E2 group(all P<0.05).Percentage of G1 phase [(53.6±3.2)%] and S phase[(29.2±4.2)%] in E2 group was significantly different with those in control group respectively(P<0.05).Percentage of G1 phase[(66.8±2.6)%,(63.1±2.6)% and (63.3±0.4)%] and S phase [(25.4±1.9)%,(25.0±3.8)% and(23.8±0.5)%] in U0126+E2 group,Bibf1120+E2 group or Ponatinib +E2 group was also significantly different with those in control group (all P<0.05); percentage of G1 phase and S phase in U0126+E2 group was significant difference with those in Bibf1120+E2 group or ponatinib+E2 group (P<0.05).The number of cell colony in E2 group (110± 17) was more than those in control group (65±8) ;the number of cell colony in U0126+E2 group(28±4),Bibf1120+E2 group(38±5) or Ponatinib+E2group(42±6) were significant different with those in E2 group (P<0.05),the number of cell colony in U0126+E2 group was significant difference with those in Bibf1 120+E2 group or Ponatinib+E2 group (all P<0.05).The results shown that the abilities of proliferation and cell migration were significantly increased in cells after estradiol stimulation.Conclusion Estradiol inducing the production of VEGF and bFGF could activate MAPK pathway through ER-independent manner,further promote development.
9.Prostate specific membrane antigen knockdown impairs the tumorigenicity of LNCaP prostate cancer cells by inhibiting the phosphatidylinositol 3-kinase/Akt signaling pathway.
Zhenghui GUO ; Yiming LAI ; Tao DU ; Yiming ZHANG ; Jieqing CHEN ; Liangkuan BI ; Tianxin LIN ; Hao LIU ; Wei WANG ; Kewei XU ; Chun JIANG ; Jinli HAN ; Caixia ZHANG ; Wen DONG ; Jian HUANG ; Hai HUANG
Chinese Medical Journal 2014;127(5):929-936
BACKGROUNDProstate specific membrane antigen (PSMA) can facilitate the growth, migration, and invasion of the LNCaP prostate cancer cell lines, but the underlying molecular mechanisms have not yet been clearly defined. Here, we investigated whether PSMA serves as a novel regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling by employing PSMA knockdown model and PI3K pharmacological inhibitor (LY294002) in LNCaP prostate cancer cells.
METHODSPSMA knockdown had been stably established by transfecting with lentivirus-mediated siRNA in our previous study. Then, LNCaP cells were divided into interference, non-interference, and blank groups. We first testified the efficacy of PSMA knockdown in our LNCaP cell line. Then, we compared the expression of PSMA and total/activated Akt by Western blotting in the above three groups with or without LY294002 treatment. Furthermore, immunocytochemistry was performed to confirm the changes of activated Akt (p-Akt, Ser473) in groups. Besides, cell proliferation, migration, and cell cycle were measured by CCK-8 assay, Transwell analysis, and Flow cytometry respectively.
RESULTSAfter PSMA knockdown, the level of p-Akt (Ser473) but not of total-Akt (Akt1/2) was significantly decreased when compared with the non-interference and blank groups. However, LY294002 administration significantly reduced the expression of p-Akt (Ser473) in all the three groups. The results of immunocytochemistry further confirmed that PSMA knockdown or LY294002 treatment was associated with p-Akt (Ser473) down-regulation. Decrease of cell proliferation, migration, and survival were also observed upon PSMA knockdown and LY294002 treatment.
CONCLUSIONSTaken together, our results reveal that PI3K/Akt signaling pathway inhibition may serve as a novel molecular mechanism in LNCaP prostate cancer cells of PSMA knockdown and suggest that Akt (Ser473) may play a critical role as a downstream signaling target effector of PSMA in this cellular model.
Antigens, Surface ; genetics ; metabolism ; Cell Line, Tumor ; Glutamate Carboxypeptidase II ; genetics ; metabolism ; Humans ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; enzymology ; genetics ; therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA Interference ; Signal Transduction ; genetics ; physiology
10.Clinical study of autoantibody spectrum against ovarian cancer associated antigens combined with CA125 in detecting and monitoring ovarian cancer
Zhijun YANG ; Guang YANG ; Yanming JIANG ; Yuliang RAN ; Zhihua YANG ; Wei ZHANG ; Jieqing ZHANG ; Zhongmian PAN ; Li LI
Chinese Journal of Obstetrics and Gynecology 2011;46(2):113-118
Objective To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA125 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. CA125 was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum ), combining autoantibody spectrum with CA125 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 CA125 (61.1% ,88.0% ,77. 1% ). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76. 6% ), compared to those of CA125 (51.1% ,P < 0. 05 ).Combining autoantibody spectrum with CA125 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 CA125 ( 61.1%, P < 0. 05; 88. 0%, P > 0. 05; 77. 1%, P < 0. 05 ). The positive ratio of combine the autoantibody spectrum with CA125 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 CA125 can improve sensitivity,specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.

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