Preoperative Butyrylcholinesterase Level as an Independent Predictor of Overall Survival in Clear Cell Renal Cell Carcinoma Patients Treated with Nephrectomy

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P=0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients

Detection of Core2 β-1,6-N-Acetylglucosaminyltransferase in Post-Digital Rectal Examination Urine Is a Reliable Indicator for Extracapsular Extension of Prostate Cancer.

To identify appropriate candidates for aggressive treatment such as radical prostatectomy or radiation therapy of localized prostate cancer (PCa), novel predictive biomarkers of PCa aggressiveness are essential. Core2 β-1,6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2-branched O-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression to the clinicopathological status of PCa. Paraffin-embedded PCa specimens were analyzed by immunohistochemistry for GCNT1 expression using a newly established mouse anti-GCNT1 mAb by ourselves. GCNT1-positive tumor showed significantly higher Gleason score and larger tumor volume. The number of GCNT1-positive cases was significantly lower in cases of organ-confined disease than in cases of extracapsular extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that detection of GCNT1 expression was an independent risk factor for PSA recurrence. We established new methods for GCNT1 detection from PCa specimens. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of PSA showed extracapsular extension. In conclusion, GCNT1 expression closely associates with the aggressive potential of PCa. Further research aims to develop GCNT1 detection in post-DRE urine as a marker for PCa aggressiveness

Detection of core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 in post-digital rectal examination urine specimens.

<p>(<b>A</b>) Post-digital rectal examination urine specimens were collected and (<b>B</b>) centrifuged. (<b>C</b>) Supernatants were collected and spotted onto a nitrocellulose membrane. (<b>D</b>) Core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 (GCNT1) was detected by an anti-GCNT1 monoclonal antibody, followed by a horseradish peroxidase (HRP)-conjugated antibody. (<b>E</b>) After treatment with a chemiluminescence reagent, the GCNT1 signal was recorded by a ChemiDoc+ system.</p

Core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 expression correlates with prostate cancer progression.

<p>(<b>A</b>) Biosynthetic pathways for <i>O</i>-glycans. (<b>B</b>) PCa specimens were incubated with an anti-core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 (GCNT1) monoclonal antibody (mAb), followed by a horseradish peroxidase (HRP)-conjugated secondary antibody. Counterstaining was performed using hematoxylin. GCNT1-positive cancer cells are brown. (<b>C</b>) Prostate-specific antigen-free survival periods were compared between GCNT1-positive and GCNT1-negative specimens. Survival was analyzed using Kaplan-Meier curves.</p

Logistic regression analyses of risk factors for extracapsular extension of prostate cancer.

<p>^a; pre-treatment prostate-specific antigen</p><p>^b; Gleason score</p><p>CI, confidence interval; GCNT1, core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1; HR, hazard ratio; PSA, prostate-specific antigen</p><p>Logistic regression analyses of risk factors for extracapsular extension of prostate cancer.</p

Univariate and multivariable analyses of risk factors for prostate-specific antigen recurrence.

<p>^a, pre-treatment prostate-specific antigen</p><p>^b, Gleason score</p><p>^c, cancer existence at the resected margin</p><p>^d, perineural invasion</p><p>^e, extracapsular extension</p><p>CI, confidence interval; GCNT1, core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1; HR, hazard ratio; PSA, prostate-specific antigen.</p><p>Univariate and multivariable analyses of risk factors for prostate-specific antigen recurrence.</p

Prostate-specific antigen concentration and core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 expression predict extracapsular extension of prostate cancer.

<p>(<b>A</b>) Prostate-specific antigen (PSA) concentration and (<b>B</b>) Core2 β-1,6-<i>N</i>-acetylglucosaminyltransferase-1 (GCNT1) expression levels were significantly higher in prostate cancer (PCa) patients with extracapsular extension than in patients with organ-confined disease. (<b>C</b>) Receiver-operator characteristic curve analysis of PSA and GCNT1 revealed that the area under the curve of PSA was 0.7455 and GCNT1 was 0.7614. (<b>D</b>) Risk stratification was established using PSA and GCNT1 to predict the outcome of local PCa. Double negative (DN)-risk (PSA < 7.52 ng/mL, GCNT1< 79.36 pg/mg), single positive (SP)-risk (PSA > 7.52 ng/mL or GCNT1 > 79.36 pg/mg) and double positive (DP)-risk (PSA > 7.52 ng/mL and GCNT1 > 79.36 pg/mg) patients are compared.</p