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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 4  |  Page : 689-692

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer


1 Department of Oncology Gynecology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China
2 Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China

Date of Web Publication13-Sep-2017

Correspondence Address:
Wei Guo
Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Bengbu 233004, Anhui Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_414_17

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 > Abstract 

Objective: The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer.
Methods: Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test.
Results: The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21–33.20) mg/mL, 4.78 (0.22–175.20) mg/mL, and 11.56 (2.028–123.66) IU/mL for NRG and 5.64 (0.50–136.80) mg/mL, 22.41 (0.56–588.90) mg/mL, and 25.41 (3.658–3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= –0.13, P = 0.56) was found in the RG patients.
Conclusion: Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Keywords: CA-125 as potential biomarkers for recurrence of cervical cancer, highly sensitive C-reactive protein, squamous cell carcinoma antigen


How to cite this article:
Guo S, Yang B, Liu H, Li Y, Li S, Ma L, Liu J, Guo W. Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer. J Can Res Ther 2017;13:689-92

How to cite this URL:
Guo S, Yang B, Liu H, Li Y, Li S, Ma L, Liu J, Guo W. Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer. J Can Res Ther [serial online] 2017 [cited 2018 May 22];13:689-92. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/689/214473


 > Introduction Top


Cervical cancer is known as one of the major malignant tumors that leads to death of many women.[1],[2] Clinical epidemiology studies have confirmed that cervical cancer is closely related to HPV infection, smoking, sex life, and pregnancy. Approximately 275,000 patients die from cervical cancer yearly.[3],[4] Tumor markers are important serological indicators for the diagnosis of malignant carcinomas. The tumor markers that are commonly used for auxiliary diagnosis of cervical cancer are carcinoembryonic antigen 125 (CA-125), cytokeratin 19 fragment antigen, sugar chain antigen 19–9 (CA19-9), squamous cell carcinoma antigen (SCC-Ag), and highly sensitive C-reactive protein (hs-CRP).[5] Cervical cancer recurrence is the main cause of treatment failure; the recurrence rate of cervical cancer is closely associated to its pathological stage. Friedlander and Grogan [4] report that the recurrence rate of cervical cancer in I B1/II A phase is 10% to 20%, whereas the recurrence rate in patients with cervical cancer in IVA phase and above is as high as 70% or more. Published studies [5],[6] showed that SCC-Ag can be used as an indicator to evaluate the therapeutic effect and condition monitoring of cervical cancer. CRP is a kind of acute response protein. In recent years, publications [7],[8],[9] have shown that CRP is elevated in the serums of patients with colorectal and ovarian cancer; however, the relationship between the expression levels of SCC-Ag, hs-CRP, and CA-125 and cervical cancer recurrence are rarely reported. In this study, we discuss the clinical value of SCC-Ag, hs-CRP, and CA-125 as tumor markers in predicting cervical cancer recurrence.


 > Methods Top


Patients inclusion

Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. The patients' inclusion criteria were as follows:[1] cervical cancer diagnosis confirmed by pathology;[2] all the patients who received radical treatment [3] and whose clinical data are complete. The exclusion criteria were [1] cervical cancer patients who did not receive radical treatment;[2] and cervical cancer patients with other malignancies. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The mean age was 50.8 ± 13.6 with the range of 33–64 for the included 86 cases. The clinical pathology was squamous cell carcinoma with 26 well-differentiation cases, 27 moderate differentiation cases, and 33 poor differentiation cases. There were 10 patients in Stage I, 43 cases in Stage II, and 33 cases in Stage III. All patients received curative treatment.

Serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, CA-125 detection

Five milliliter peripheral blood was collected from the patients and 4000 r/min centrifugation for 15 min and the serum was separated and stored in the refrigerator at −80°C until use. The serum SCC-Ag, hs-CRP, and CA-125 were examined by enzyme-linked immunosorbent assay according to the standard operating procedure or reagent instruction.[5],[6],[7]

Statistical analysis

All the statistical analyses were done by SPSS17.0 software (Stata11.0 (http://www.stata.com)). The measurement data such as serum level of SCC-Ag, hs-CRP, and CA-125 were expressed by mean ± standard deviation and analyzed by Student's t-test. The enumeration data were expressed with a relative number, and the comparison between groups was made based on the Chi-square test. The recurrence prediction sensitivity and specificity was calculated by the equation: sensitivity = true positive/(true positive + false negative), specificity = true negative/(true negative + false positive). The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction efficacy of serum SCC-Ag, hs-CRP, and CA-125 as biomarkers for cervical cancer recurrence risk.


 > Results Top


Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125

The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21–33.20) mg/mL, 4.78 (0.22–175.20) mg/mL, and 11.56 (2.028–123.66) IU/mL for NRG and 5.64 (0.50–136.80) mg/mL, 22.41 (0.56–588.90) mg/mL, and 25.41 (3.658–3687.00) IU/mL for RG, respectively [Figure 1]. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG were significant higher than those of NRG (P < 0.05).
Figure 1: The scatter plot of serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 for cervical cancer patients of nonrecurrence and recurrence groups

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Recurrence prediction value of serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125

The recurrence prediction sensitivity was 0.74, 0.65, and 0.74, specificity was 0.65, 0.63, and 0.58 [Table 1], AUC under the ROC curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125 [Figure 2].
Table 1: The diagnostic value of serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and carcinoembryonic antigen 125 for cervical cancer

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Figure 2: The receiver operating characteristic curve of serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as biomarker for cervical cancer diagnosis ((a) Roc curve for SCC-Ag; (b) Roc curve for hs-CRP; (c) Roc curve for CA-125)

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Correlation between serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125

The correlation between serum SCC-Ag, hs-CRP, and CA-125 was analyzed by Pearson correlation test. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= −0.13, P = 0.56) was found in the RG patients [Figure 3].
Figure 3: Pearson correlation between serum squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 cervical cancer

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 > Discussion Top


Clinical evidence [10],[11] shows a low cure rate after cervical cancer recurrence; due to patients' lower sensitivity to radiotherapy and chemotherapy, the retreatment effect is poor. Moreover, a recurrence probability of over 80% of patients with cervical cancer recurrence in 2 years is higher; and 5-year survival rate is <20%. Thus, early detection of some latent recurrence in patients with cervical cancer can save time for treatment and improve the survival rate. The study detects SCC-Ag, hs-CRP, and CA-125 in the serums of discharged patients who have regular follow-up for cervical cancer and finds that SCC-Ag, hs-CRP, and CA-125 levels in serum are significantly increased in patients with cervical cancer recurrence. The results in this study are consistent with the previous results. The diagnostic value of SCC-Ag in cervical cancer follow-up has been confirmed, and Lee et al.[12] report that SCC-Ag has increased in most of patients with cervical cancer recurrence. Forni et al.[13] assumed that SCC-Ag increases 5 months earlier than the recurrence of clinical symptoms in patients with cervical cancer recurrence. Another study [14] shows that SCC-Ag, which can also be used to monitor the pathological process of malignant tumors, is of great significance for the prognosis of SCC.

At present, human papillomavirus infection is the most common cause, which leads to cervical cancer; almost all patients with cervical cancer suffer from positive papillomavirus infection, which causes the increase of inflammatory mediators in the coexistence of inflammation and malignant tumors.[15] CRP is an acute response protein; studies [7],[16],[17],[18] have found that CRP increases in the serums of patients with colorectal and ovarian cancer. Although the increase of serum CRP is a nonspecific response to many diseases, CRP test in the early diagnosis, differential diagnosis, and observation of curative effect is still of great significance. Our results also confirm the role of CRP in the early diagnosis of cervical cancer recurrence. SCC-Ag and CRP have certain values in the early diagnosis of cervical cancer recurrence.


 > Conclusion Top


We believe that the test for SCC-Ag, hs-CRP, and CA-125 expression levels in serum is a sensitive and specific method to predict the risk of cervical cancer recurrence. As an important follow-up test for cervical cancer treatment, the imaging examination combined with serum SCC-Ag, hs-CRP, and CA-125 detection can improve the positive rate of cervical cancer recurrence and improve the prognosis of the patients. However, this study also has two major limitations: first, the sample size is small. There are only 86 cases included in this study. The small sample size made the statistical power limited. Second, the study is retrospectively designed with heterogeneity between the RG and NRG groups. Therefore, prospective multicenter randomized clinical controlled studies need to further evaluate the serum expression level levels of SCC-Ag, hs-CRP, and CA-125 as potential serum biomarkers for recurrence of cervical cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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