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High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.

Kawate T, Iwaya K, Koshikawa K, Moriya T, Yamasaki T, Hasegawa S, Kaise H, Fujita T, Matsuo H, Nakamura T, Ishikawa T, Hiroi S, Iguchi-Ariga SM, Ariga H, Murota K, Fujimori M, Yamamoto J, Matsubara O, Kohno N - Cancer Sci. (2015)

Bottom Line: Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA.DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis.Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, National Defense Medical College, Saitama, Japan.

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Mean level of DJ-1 in serum, and the expression profile of its isoforms, in breast cancer and non-cancerous groups. (a) Mean levels of DJ-1 protein in sera from breast cancer and non-cancerous groups. In sera from the breast cancer group (n = 180), the mean level of DJ-1 protein was 42.7 ng/mL, whereas that in the non-cancerous group (n = 300) was 28.3 ng/mL. There was a significant difference in the mean levels between the two groups (P = 0.019). Data are means of three independent experiments with SE. (b) DJ-1 isoform patterns of three representative cancer cases. (c) Two-dimensional Western blot detection of DJ-1 isoforms shown as an LAS3000 image with molecular weight. Intensity of each isoelectric spot was semiquantified as a peak of signal intensity that was drawn by ImageQuant TL 8.1 software. The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at pI 6.3 in all cancer cases. (c) DJ-1 isoform patterns of three representative non-cancerous cases. DJ-1 isoform image and its semiquantified graph are shown in the same manner as (b). The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at the acidic side (pI 5.7, 5.9, 5.9) in each non-cancerous case. The y-axis is the signal intensity drawn by ImageQuant TL 8.1 software. (d) Mean levels of DJ-1 at pI 6.3 in the sera of abnormally high DJ-1 in breast cancer and non-cancerous groups. The mean level, calculated by the ratio of isoform peaks, of DJ-1 at pI 6.3 from sera of 11 cancerous cases (40.6 ng/mL) was significantly higher than that from 6 non-cancer cases (3.5 ng/mL) (P = 0.0017). Data are the mean of three independent experiments with SE.
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fig01: Mean level of DJ-1 in serum, and the expression profile of its isoforms, in breast cancer and non-cancerous groups. (a) Mean levels of DJ-1 protein in sera from breast cancer and non-cancerous groups. In sera from the breast cancer group (n = 180), the mean level of DJ-1 protein was 42.7 ng/mL, whereas that in the non-cancerous group (n = 300) was 28.3 ng/mL. There was a significant difference in the mean levels between the two groups (P = 0.019). Data are means of three independent experiments with SE. (b) DJ-1 isoform patterns of three representative cancer cases. (c) Two-dimensional Western blot detection of DJ-1 isoforms shown as an LAS3000 image with molecular weight. Intensity of each isoelectric spot was semiquantified as a peak of signal intensity that was drawn by ImageQuant TL 8.1 software. The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at pI 6.3 in all cancer cases. (c) DJ-1 isoform patterns of three representative non-cancerous cases. DJ-1 isoform image and its semiquantified graph are shown in the same manner as (b). The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at the acidic side (pI 5.7, 5.9, 5.9) in each non-cancerous case. The y-axis is the signal intensity drawn by ImageQuant TL 8.1 software. (d) Mean levels of DJ-1 at pI 6.3 in the sera of abnormally high DJ-1 in breast cancer and non-cancerous groups. The mean level, calculated by the ratio of isoform peaks, of DJ-1 at pI 6.3 from sera of 11 cancerous cases (40.6 ng/mL) was significantly higher than that from 6 non-cancer cases (3.5 ng/mL) (P = 0.0017). Data are the mean of three independent experiments with SE.

Mentions: The mean level of DJ-1 in the breast cancer group was 42.7 ng/mL, whereas the mean level of DJ-1 in the non-cancerous group was 28.3 ng/mL; serum levels of DJ-1 were significantly different between the breast cancer and non-cancerous groups (P = 0.019) (Fig.1a). Table1 shows the association between DJ-1 levels and the pathological TNM classification in the breast cancer group. Significantly higher levels of DJ-1 were detected in cases with tumor sizes >5 cm, or where there was evidence of direct invasion to the chest wall or skin, irrespective of tumor size (T3 or T4), than in cases with tumor sizes ≤5 cm (T1 or T2) (P < 0.0001). The presence of both lymph node metastasis (P = 0.00017) and distant metastasis (P < 0.0001) were associated with significantly increased serum levels of DJ-1. These data suggest that serum levels of DJ-1 are elevated in the presence of cancer and correlate with the extent of clinical cancer. Table2 shows the association between biologic markers and DJ-1 levels. Higher levels of DJ-1 were significantly detected in negative estrogen receptor status (P = 0.012), negative progesterone receptor status (P = 0.013), and high Ki-67 labeling index (P = 0.022); however, DJ-1 levels did not correlate with HER2 status.


High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.

Kawate T, Iwaya K, Koshikawa K, Moriya T, Yamasaki T, Hasegawa S, Kaise H, Fujita T, Matsuo H, Nakamura T, Ishikawa T, Hiroi S, Iguchi-Ariga SM, Ariga H, Murota K, Fujimori M, Yamamoto J, Matsubara O, Kohno N - Cancer Sci. (2015)

Mean level of DJ-1 in serum, and the expression profile of its isoforms, in breast cancer and non-cancerous groups. (a) Mean levels of DJ-1 protein in sera from breast cancer and non-cancerous groups. In sera from the breast cancer group (n = 180), the mean level of DJ-1 protein was 42.7 ng/mL, whereas that in the non-cancerous group (n = 300) was 28.3 ng/mL. There was a significant difference in the mean levels between the two groups (P = 0.019). Data are means of three independent experiments with SE. (b) DJ-1 isoform patterns of three representative cancer cases. (c) Two-dimensional Western blot detection of DJ-1 isoforms shown as an LAS3000 image with molecular weight. Intensity of each isoelectric spot was semiquantified as a peak of signal intensity that was drawn by ImageQuant TL 8.1 software. The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at pI 6.3 in all cancer cases. (c) DJ-1 isoform patterns of three representative non-cancerous cases. DJ-1 isoform image and its semiquantified graph are shown in the same manner as (b). The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at the acidic side (pI 5.7, 5.9, 5.9) in each non-cancerous case. The y-axis is the signal intensity drawn by ImageQuant TL 8.1 software. (d) Mean levels of DJ-1 at pI 6.3 in the sera of abnormally high DJ-1 in breast cancer and non-cancerous groups. The mean level, calculated by the ratio of isoform peaks, of DJ-1 at pI 6.3 from sera of 11 cancerous cases (40.6 ng/mL) was significantly higher than that from 6 non-cancer cases (3.5 ng/mL) (P = 0.0017). Data are the mean of three independent experiments with SE.
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fig01: Mean level of DJ-1 in serum, and the expression profile of its isoforms, in breast cancer and non-cancerous groups. (a) Mean levels of DJ-1 protein in sera from breast cancer and non-cancerous groups. In sera from the breast cancer group (n = 180), the mean level of DJ-1 protein was 42.7 ng/mL, whereas that in the non-cancerous group (n = 300) was 28.3 ng/mL. There was a significant difference in the mean levels between the two groups (P = 0.019). Data are means of three independent experiments with SE. (b) DJ-1 isoform patterns of three representative cancer cases. (c) Two-dimensional Western blot detection of DJ-1 isoforms shown as an LAS3000 image with molecular weight. Intensity of each isoelectric spot was semiquantified as a peak of signal intensity that was drawn by ImageQuant TL 8.1 software. The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at pI 6.3 in all cancer cases. (c) DJ-1 isoform patterns of three representative non-cancerous cases. DJ-1 isoform image and its semiquantified graph are shown in the same manner as (b). The vertical axis shows signal intensity, and the horizontal axis shows the pI. The highest peak was detected at the acidic side (pI 5.7, 5.9, 5.9) in each non-cancerous case. The y-axis is the signal intensity drawn by ImageQuant TL 8.1 software. (d) Mean levels of DJ-1 at pI 6.3 in the sera of abnormally high DJ-1 in breast cancer and non-cancerous groups. The mean level, calculated by the ratio of isoform peaks, of DJ-1 at pI 6.3 from sera of 11 cancerous cases (40.6 ng/mL) was significantly higher than that from 6 non-cancer cases (3.5 ng/mL) (P = 0.0017). Data are the mean of three independent experiments with SE.
Mentions: The mean level of DJ-1 in the breast cancer group was 42.7 ng/mL, whereas the mean level of DJ-1 in the non-cancerous group was 28.3 ng/mL; serum levels of DJ-1 were significantly different between the breast cancer and non-cancerous groups (P = 0.019) (Fig.1a). Table1 shows the association between DJ-1 levels and the pathological TNM classification in the breast cancer group. Significantly higher levels of DJ-1 were detected in cases with tumor sizes >5 cm, or where there was evidence of direct invasion to the chest wall or skin, irrespective of tumor size (T3 or T4), than in cases with tumor sizes ≤5 cm (T1 or T2) (P < 0.0001). The presence of both lymph node metastasis (P = 0.00017) and distant metastasis (P < 0.0001) were associated with significantly increased serum levels of DJ-1. These data suggest that serum levels of DJ-1 are elevated in the presence of cancer and correlate with the extent of clinical cancer. Table2 shows the association between biologic markers and DJ-1 levels. Higher levels of DJ-1 were significantly detected in negative estrogen receptor status (P = 0.012), negative progesterone receptor status (P = 0.013), and high Ki-67 labeling index (P = 0.022); however, DJ-1 levels did not correlate with HER2 status.

Bottom Line: Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA.DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis.Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, National Defense Medical College, Saitama, Japan.

Show MeSH
Related in: MedlinePlus