Limits...
Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and prognosis of hepatocellular carcinoma.

Yu D, Shi X, Meng G, Chen J, Yan C, Jiang Y, Wei J, Ding Y - Oncotarget (2015)

Bottom Line: We found that GLS1 was highly expressed in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes.We found that high expression of GLS1 and low expression of GLS2 in HCC correlated with survival time of HCC patients.These findings indicate that GLS1 expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China.

ABSTRACT
The lack of sensitive and specific biomarkers hinders pathological diagnosis and prognosis for hepatocellular carcinoma (HCC). Since glutaminolysis plays a crucial role in carcinogenesis and progression, we sought to determine if the expression of kidney-type and liver-type glutaminases (GLS1 and GLS2) were informative for pathological diagnosis and prognosis of HCC. We compared the expression of GLS1 and GLS2 in a large set of clinical samples including HCC, normal liver, and other liver diseases. We found that GLS1 was highly expressed in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes. The sensitivity and specificity of GLS1 for HCC were 96.51% and 75.21%, respectively. A metabolic switch from GLS2 to GLS1 was observed in a series of tissues representing progressive pathologic states mimicking HCC oncogenic transformation, including normal liver, fibrotic liver, dysplasia nodule, and HCC. We found that high expression of GLS1 and low expression of GLS2 in HCC correlated with survival time of HCC patients. Expression of GLS1 and GLS2 were independent indexes for survival time; however, prognosis was predominantly determined by the level of GLS1 expression. These findings indicate that GLS1 expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of HCC.

No MeSH data available.


Related in: MedlinePlus

Tissue microarray analysis validates the sensitivity and specificity of GLS1 for diagnosis of HCC(A) The expression of GLS1 was determined by immunohistochemical staining on tissue microarrays. Representative staining of each pathological category is presented. Bars = 100 μm. (B) Quantitation of expression intensity and frequency of GLS1 in all tissue punches. LDs, liver diseases, including cholelithiasis, fatty liver and fibrotic liver. (C) Sensitivity and specificity of GLS1 for HCC analyzed by ROC curve (dark line). Positive GLS1 staining in HCC was counted by two thresholds: strongly stained (open dot) and weakly stained (filled dot). The AUC value is 0.888.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4480704&req=5

Figure 3: Tissue microarray analysis validates the sensitivity and specificity of GLS1 for diagnosis of HCC(A) The expression of GLS1 was determined by immunohistochemical staining on tissue microarrays. Representative staining of each pathological category is presented. Bars = 100 μm. (B) Quantitation of expression intensity and frequency of GLS1 in all tissue punches. LDs, liver diseases, including cholelithiasis, fatty liver and fibrotic liver. (C) Sensitivity and specificity of GLS1 for HCC analyzed by ROC curve (dark line). Positive GLS1 staining in HCC was counted by two thresholds: strongly stained (open dot) and weakly stained (filled dot). The AUC value is 0.888.

Mentions: Having shown that GLS1 possesses the sensitivity and specificity for pathologic diagnosis of HCC, we sought to validate this finding by tissue microarray (TMA, OD-CT-DgLiv01 with 478 spots) analysis. The liver tissues were confirmed and categorized into normal liver, dysplasia nodule, HCC and other liver diseases. We found that GLS1 was negatively stained in hepatocytes of normal liver, and cholelithiasis, weakly stained in tissues of fatty liver, fibrotic liver, and dysplasia nodules, and strongly stained in tumor cells of HCC (Figure 3A). The frequency and intensity of GLS1 staining are summarized in Figure 3B. The intensity of GLS1 staining in HCC was much higher than in any other tissue. When the cut-off for positivity for GLS1 was set at strongly positive (++) staining intensity, the senstivity and specificity of GLS1 for HCC was 98.39% and 76.64%. If the cut-off for positivity for GLS1 was set at weakly positive (+) staining intensity, the senstivity was decreased to 76.65% while the specificity was increased to 85.71%. The AUC (area under the receiver operating characteristic curve) value was up to 0.888 (Figure 3C). These results provide validation for our proposed use of GLS1 as a sensitive and specific diagnostic marker for HCC.


Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and prognosis of hepatocellular carcinoma.

Yu D, Shi X, Meng G, Chen J, Yan C, Jiang Y, Wei J, Ding Y - Oncotarget (2015)

Tissue microarray analysis validates the sensitivity and specificity of GLS1 for diagnosis of HCC(A) The expression of GLS1 was determined by immunohistochemical staining on tissue microarrays. Representative staining of each pathological category is presented. Bars = 100 μm. (B) Quantitation of expression intensity and frequency of GLS1 in all tissue punches. LDs, liver diseases, including cholelithiasis, fatty liver and fibrotic liver. (C) Sensitivity and specificity of GLS1 for HCC analyzed by ROC curve (dark line). Positive GLS1 staining in HCC was counted by two thresholds: strongly stained (open dot) and weakly stained (filled dot). The AUC value is 0.888.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480704&req=5

Figure 3: Tissue microarray analysis validates the sensitivity and specificity of GLS1 for diagnosis of HCC(A) The expression of GLS1 was determined by immunohistochemical staining on tissue microarrays. Representative staining of each pathological category is presented. Bars = 100 μm. (B) Quantitation of expression intensity and frequency of GLS1 in all tissue punches. LDs, liver diseases, including cholelithiasis, fatty liver and fibrotic liver. (C) Sensitivity and specificity of GLS1 for HCC analyzed by ROC curve (dark line). Positive GLS1 staining in HCC was counted by two thresholds: strongly stained (open dot) and weakly stained (filled dot). The AUC value is 0.888.
Mentions: Having shown that GLS1 possesses the sensitivity and specificity for pathologic diagnosis of HCC, we sought to validate this finding by tissue microarray (TMA, OD-CT-DgLiv01 with 478 spots) analysis. The liver tissues were confirmed and categorized into normal liver, dysplasia nodule, HCC and other liver diseases. We found that GLS1 was negatively stained in hepatocytes of normal liver, and cholelithiasis, weakly stained in tissues of fatty liver, fibrotic liver, and dysplasia nodules, and strongly stained in tumor cells of HCC (Figure 3A). The frequency and intensity of GLS1 staining are summarized in Figure 3B. The intensity of GLS1 staining in HCC was much higher than in any other tissue. When the cut-off for positivity for GLS1 was set at strongly positive (++) staining intensity, the senstivity and specificity of GLS1 for HCC was 98.39% and 76.64%. If the cut-off for positivity for GLS1 was set at weakly positive (+) staining intensity, the senstivity was decreased to 76.65% while the specificity was increased to 85.71%. The AUC (area under the receiver operating characteristic curve) value was up to 0.888 (Figure 3C). These results provide validation for our proposed use of GLS1 as a sensitive and specific diagnostic marker for HCC.

Bottom Line: We found that GLS1 was highly expressed in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes.We found that high expression of GLS1 and low expression of GLS2 in HCC correlated with survival time of HCC patients.These findings indicate that GLS1 expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China.

ABSTRACT
The lack of sensitive and specific biomarkers hinders pathological diagnosis and prognosis for hepatocellular carcinoma (HCC). Since glutaminolysis plays a crucial role in carcinogenesis and progression, we sought to determine if the expression of kidney-type and liver-type glutaminases (GLS1 and GLS2) were informative for pathological diagnosis and prognosis of HCC. We compared the expression of GLS1 and GLS2 in a large set of clinical samples including HCC, normal liver, and other liver diseases. We found that GLS1 was highly expressed in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes. The sensitivity and specificity of GLS1 for HCC were 96.51% and 75.21%, respectively. A metabolic switch from GLS2 to GLS1 was observed in a series of tissues representing progressive pathologic states mimicking HCC oncogenic transformation, including normal liver, fibrotic liver, dysplasia nodule, and HCC. We found that high expression of GLS1 and low expression of GLS2 in HCC correlated with survival time of HCC patients. Expression of GLS1 and GLS2 were independent indexes for survival time; however, prognosis was predominantly determined by the level of GLS1 expression. These findings indicate that GLS1 expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of HCC.

No MeSH data available.


Related in: MedlinePlus