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      Value of TCT combined with serum CA153 and CA50 in early diagnosis of cervical cancer and precancerous lesions

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          Abstract

          Objectives:

          To determine the application value of thinprep cytologic test (TCT) combined with serum carbohydrate antigen 153 (CA153) and carbohydrate antigen 50 (CA50) detection in the early diagnosis and screening of cervical cancer and precancerous lesions.

          Methods:

          A total of 187 females with cervical lesions admitted to Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2017 to December 2018 were selected and divided into two groups: the cervical cancer group and the cervical precancerous lesion group, with 16 cases in the cervical cancer group and 171 cases in the cervical precancerous lesion group (cervical precancerous lesions were divided into 63 cases of the CNI group, 59 cases of the CNII group and 49 cases of the CNIII group). During the same period, 106 healthy females were selected as the healthy group. The serum tumor markers CA153 and CA50 of all subjects were detected by chemiluminescence method; The diagnostic value of TCT combined with serum CA153 and CA50 in cervical cancer and precancerous lesions was analyzed with colposcopy pathological diagnosis results as gold standard; ROC curve was drawn to evaluate the diagnostic value of serum TCT, CA153 and CA50 in cervical cancer and precancerous lesions.

          Results:

          The levels of serum CA153 and CA50 in the cervical cancer group were significantly higher than those in the cervical precancerous lesion group and the healthy group (p< 0.05), and the levels of serum CA153 and CA50 in the cervical precancerous lesion group were significantly higher than those in the healthy group (p< 0.05). The sensitivity of TCT, serum CA153 and serum CA50 in the single detection of cervical cancer and precancerous lesions was 95.93%, 97.54% and 96.00%, the specificity was 59.41%, 60.23%, 60.12%, the accuracy was 74.74%, 75.77%, 75.43%, the positive predictive value was 62.03%, 63.64%, 63.10%, and the negative predictive value was 96.22%, 97.17% and 95.28%, respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TCT combined with serum CA153 and CA50 were 96.77%, 73.19%, 85.67%, 80.21% and 95.28%, respectively. ROC curve showed that the area under the curve (AUC) of TCT and serum CA153 and CA50 in the single detection of cervical cancer and precancerous lesions was 0.791, 0.864 and 0.787, respectively, the AUC of combined detection of TCT and serum CA153 and CA50 in patients with cervical cancer and precancerous lesions was 0.877, which was significantly higher than that of single detection (p< 0.05).

          Conclusions:

          TCT combined with serum CA153 and CA50 has been reported as a treatment regimen with high accuracy, which has a high diagnostic efficiency for early diagnosis of cervical cancer and precancerous lesions, and can significantly improve the sensitivity.

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          Most cited references22

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          Serum CA153 as biomarker for cancer and noncancer diseases.

          CA153 was originally discovered as a tumor antigen recognized by two monoclonal antibodies DF3 and 115D8 simultaneously. Subsequent studies showed that DF3 recognizes the core protein of mucin1 (MUC1 or CD227) whereas 115D8 recognizes part of the glycan chains on MUC1. MUC1 is a highly glycosylated transmembrane protein expressed on the mucosal surfaces of epithelial cells in lung, breast, stomach, gallbladder, lymph node, colon, rectum, and pancreas. The increased serum levels of CA153 have been established as a biomarker for breast cancer diagnosis since 1980s. However, it is unknown if elevated serum CA153 levels were also associated with other cancers and noncancer diseases. In current study, a total of 19,789 clinical lab test results of serum CA153 levels from healthy individuals and patients with 30 different types of diseases during the past 5 years were retrieved and analyzed. According to the mean (SD), median, and p (-Log10p) values calculated, we found that patients suffering lung, breast, ovarian cancers, nephrotic syndrome, type 2 diabetes, endometrial cancer, coronary heart disease, cervical cancer, uremia, and other 12 diseases plus healthy controls >65 years old had significantly (p 1.30) increased median serum CA153 levels compared to that of healthy controls. Moreover, patients with lymphoma had the highest mean and the biggest SD value for serum CA153. Based on these data and the documented evidence, we proposed that the increased serum CA153 levels might be associated with pathological leakage of the epithelial cell product into the blood circulation in addition to the decreased CA153 clearance rate.
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            Use of CA15-3 for screening breast cancer: An antibody-lectin sandwich assay for detecting glycosylation of CA15-3 in sera

            Elevated serum CA15-3 assessed by enzyme-linked immunosorbent assay (ELISA) has been considered a diagnostic marker of breast cancer. However, accumulating data indicate that the current ELISA system for detecting CA15-3, which targets the peptide backbone of CA15-3, is not sufficiently sensitive to detect early or localized breast cancer. In the present study, we designed an antibody-lectin sandwich assay detecting glycosylation of CA15-3 in patients with breast cancer. Immobilized anti-CA15-3 monoclonal antibody captures CA15-3 in serum, and glycosylation of the CA15-3 is detected with Concanavalin A (ConA) lectin, which preferentially bind high-mannose N-glycans. ConA provided the best signal for detecting serum CA15-3 among 9 types of lectin, Since CA15-3 is a heavily glycosylated protein, detecting the glycosylation of CA15-3 should be a much more sensitive way to assess CA15-3 than the current ELISA method. Linear responses were obtained in the anti-CA15-3 antibody-ConA sandwich assay when sera were diluted up to 2000-fold. This dilution factor is comparable with that of the current ELISA system which allows 50- to 100-fold serum dilutions. The glycosylation level of CA15-3 was found to increase with increasing breast cancer stage in the sandwich assay. The assay system appeared to efficiently discriminate breast cancer stage I (sensitivity: 63%, specificity: 69%), IIA (sensitivity: 77%, specificity: 75%), IIB (sensitivity: 69%, specificity: 86%) and III (sensitivity: 80%, specificity: 65%) from benign breast disease. The antibody-lectin sandwich assay shows promise as a new prospect for the early detection of breast cancer.
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              Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan

              Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. For in vitro experiments, two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models. Out of 147 primary cervical cancers, 113 were squamous cell carcinomas (SCCs), and 34 were adenocarcinoma/adenosquamous carcinomas. Moderate to strong diffuse staining was seen in 95% (108/113) of SCCs, and 81% (29/34) of adenocarcinoma/adenosquamous cancers on immunohistochemistry. Trop-2 positive cell lines were highly sensitive to sacituzumab govitecan in vitro, with IC50 values in the range of 0.18 to 0.26 nM (p = 0.02, and p = 0.04 for CVX-8, and ADX-3, respectively). In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p < 0.0001, and p = 0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p = 0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.
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                Author and article information

                Journal
                Pak J Med Sci
                Pak J Med Sci
                Pakistan Journal of Medical Sciences
                Professional Medical Publications (Pakistan )
                1682-024X
                1681-715X
                Jul-Aug 2022
                : 38
                : 6
                : 1471-1476
                Affiliations
                [1 ]Heyue Li, Division of Urological and Reproductive Medicine, Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
                [2 ]Linxia Li, Division of Urological and Reproductive Medicine, Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
                [3 ]Jianming Sun, Division of Urological and Reproductive Medicine, Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
                [4 ]Shengdong Dong, Division of Urological and Reproductive Medicine, Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
                [5 ]Hong Li, Division of Urological and Reproductive Medicine, Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
                Author notes
                Correspondence: Linxia Li, Division of Urological and Reproductive Medicine, Shanghai 7 th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China. Email: qyfck2021@ 123456163.com
                Article
                PJMS-38-1471
                10.12669/pjms.38.6.5503
                9378374
                35991263
                6c285d2f-b942-4aa0-afac-cbb97e248937
                Copyright: © Pakistan Journal of Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 October 2021
                : 04 March 2022
                : 03 April 2022
                Categories
                Original Article

                cervical cancer,thinprep cytologic test,carbohydrate antigen 153,carbohydrate antigen 50,early diagnosis

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