Evaluation of β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer

Kunle Odunsi, Sharad A Ghamande, E. V. Chandrasekaran, Alyssa Ta, Kirsten B. Moysich, Deborah Driscoll, Khushi Matta, Shashikant Lele

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

OBJECTIVE: Approximately 50% of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:β1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:β1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate - carbon 14 - labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:β1,6GalNAcα-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:β1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated. RESULTS: There was a significant correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels before the operation (r = 0.57; P = .03) but not before second-look surgery (r = 0.10; P = .57). Thirteen patients (39.4%) had residual disease at second-look surgery. Elevated N-acetylglucosamine:β-1, 4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9%). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:β1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77%, 45%, 48%, and 77%, respectively. CONCLUSION: Our comparative study of serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60% of patients with normal serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N-acetylglucosamine:β1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:β1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.

Original languageEnglish (US)
Pages (from-to)575-580
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume187
Issue number3
DOIs
StatePublished - Jan 1 2002

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Galactosyltransferases
Acetylglucosamine
Ovarian Neoplasms
Biomarkers
Second-Look Surgery
Serum
Therapeutics
CA-125 Antigen
Residual Volume
Physiologic Monitoring
Tumor Biomarkers
Drug Therapy
Sensitivity and Specificity

Keywords

  • Second-look surgery
  • Serum CA 125
  • β1,4-Galactosyltransferase

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Evaluation of β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. / Odunsi, Kunle; Ghamande, Sharad A; Chandrasekaran, E. V.; Ta, Alyssa; Moysich, Kirsten B.; Driscoll, Deborah; Matta, Khushi; Lele, Shashikant.

In: American Journal of Obstetrics and Gynecology, Vol. 187, No. 3, 01.01.2002, p. 575-580.

Research output: Contribution to journalArticle

Odunsi, Kunle ; Ghamande, Sharad A ; Chandrasekaran, E. V. ; Ta, Alyssa ; Moysich, Kirsten B. ; Driscoll, Deborah ; Matta, Khushi ; Lele, Shashikant. / Evaluation of β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. In: American Journal of Obstetrics and Gynecology. 2002 ; Vol. 187, No. 3. pp. 575-580.
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abstract = "OBJECTIVE: Approximately 50{\%} of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:β1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:β1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate - carbon 14 - labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:β1,6GalNAcα-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:β1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated. RESULTS: There was a significant correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels before the operation (r = 0.57; P = .03) but not before second-look surgery (r = 0.10; P = .57). Thirteen patients (39.4{\%}) had residual disease at second-look surgery. Elevated N-acetylglucosamine:β-1, 4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9{\%}). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:β1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77{\%}, 45{\%}, 48{\%}, and 77{\%}, respectively. CONCLUSION: Our comparative study of serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60{\%} of patients with normal serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N-acetylglucosamine:β1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:β1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.",
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T1 - Evaluation of β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer

AU - Odunsi, Kunle

AU - Ghamande, Sharad A

AU - Chandrasekaran, E. V.

AU - Ta, Alyssa

AU - Moysich, Kirsten B.

AU - Driscoll, Deborah

AU - Matta, Khushi

AU - Lele, Shashikant

PY - 2002/1/1

Y1 - 2002/1/1

N2 - OBJECTIVE: Approximately 50% of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:β1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:β1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate - carbon 14 - labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:β1,6GalNAcα-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:β1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated. RESULTS: There was a significant correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels before the operation (r = 0.57; P = .03) but not before second-look surgery (r = 0.10; P = .57). Thirteen patients (39.4%) had residual disease at second-look surgery. Elevated N-acetylglucosamine:β-1, 4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9%). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:β1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77%, 45%, 48%, and 77%, respectively. CONCLUSION: Our comparative study of serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60% of patients with normal serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N-acetylglucosamine:β1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:β1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.

AB - OBJECTIVE: Approximately 50% of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:β1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:β1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:β1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate - carbon 14 - labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:β1,6GalNAcα-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:β1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated. RESULTS: There was a significant correlation between serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels before the operation (r = 0.57; P = .03) but not before second-look surgery (r = 0.10; P = .57). Thirteen patients (39.4%) had residual disease at second-look surgery. Elevated N-acetylglucosamine:β-1, 4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9%). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:β1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77%, 45%, 48%, and 77%, respectively. CONCLUSION: Our comparative study of serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60% of patients with normal serum CA 125 and N-acetylglucosamine:β1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N-acetylglucosamine:β1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:β1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.

KW - Second-look surgery

KW - Serum CA 125

KW - β1,4-Galactosyltransferase

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