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Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study.

Hong CQ, Zhang F, You YJ, Qiu WL, Giuliano AE, Cui XJ, Zhang GJ, Cui YK - BMC Cancer (2015)

Bottom Line: Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145).Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001).In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.

View Article: PubMed Central - PubMed

Affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China. chaoqunhong@gmail.com.

ABSTRACT

Background: Chromosome 1 open reading frame 63 (C1orf63) is located on the distal short arm of chromosome 1, whose allelic loss has been observed in several human cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T lymphocytes, which suggests it might be involved in cell cycle control, a common mechanism for carcinogenesis. Here we investigated the expression and clinical implication of C1orf63 in breast cancer.

Methods: Paraffin-embedded specimens, clinicopathological features and follow-up data of the breast cancer patients were collected. Publicly available microarray and RNA-seq datasets used in this study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool was also adopted. The expression of C1orf63 and CDK10, one known cell cycle-dependent tumor suppressor in breast cancer, was assessed by immunohistochemistry. Western blotting was performed to detect C1orf63 protein in human breast cancer cell lines, purchased from the Culture Collection of the Chinese Academy of Sciences, Shanghai.

Results: In a group of 12 human breast tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression both in breast cancer and several other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma. In another group of 182 breast cancer patients, C1orf63 expression in tumors was not correlated with any clinicopathological features collected in this study. Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145). However, the analyses of KM plotter displayed a valid relationship between C1orf63 and RFS (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression was an independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001).

Conclusions: Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.

No MeSH data available.


Related in: MedlinePlus

C1orf63 expression in human breast tissues and its correlation with CDK10. IHC detected staining of CDK10 in tumors (a, i) and absent staining for CDK10 in tumors (a, ii); CDK10 was significantly correlated with C1orf63 in patients with breast cancer from datasets E-GEOD-4922 (b, i), E-GEOD-5847 (b, ii), E-GEOD-23988 (b, iii) and E-TABM-158 (b, iv). The Y-axis and X-axis respectively represented the mRNA expression of CDK10 and C1orf63 on the log-2 scale
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Fig5: C1orf63 expression in human breast tissues and its correlation with CDK10. IHC detected staining of CDK10 in tumors (a, i) and absent staining for CDK10 in tumors (a, ii); CDK10 was significantly correlated with C1orf63 in patients with breast cancer from datasets E-GEOD-4922 (b, i), E-GEOD-5847 (b, ii), E-GEOD-23988 (b, iii) and E-TABM-158 (b, iv). The Y-axis and X-axis respectively represented the mRNA expression of CDK10 and C1orf63 on the log-2 scale

Mentions: CDK10 has been shown to play a role in cellular progression as well as a known prognostic factor predicting better outcome for breast cancers. Given the suggested role of C1orf63 on cell cycle exit [8], and its capability to predict better prognosis for breast cancers (Fig. 3B and Table 8), we thus examined the relationship between C1orf63 and CDK10. We firstly took advantage of four publicly available microarray datasets, each including a cohort of patients with breast cancer, to evaluate whether mRNA expression of C1orf63 could be related to that of CDK10. As shown in Fig. 5B, for mRNA expression, C1orf63 was positively correlated with CDK10, and the RNA-seq dataset also displayed a significant correlation between these two genes (r = 0.521, P < 0.001; Table 2). Further, CDK10 protein expression was examined by IHC. As shown in Fig. 5Ai, CDK10 primarily expressed in the nucleus and the relationship between the IHC scores of CDK 10 and C1orf63 was consistent with that of their mRNA expressions, which demonstrated that C1orf63 expression was positively correlated with CDK10 (rs = 0.391; P < 0.001).Fig. 5


Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study.

Hong CQ, Zhang F, You YJ, Qiu WL, Giuliano AE, Cui XJ, Zhang GJ, Cui YK - BMC Cancer (2015)

C1orf63 expression in human breast tissues and its correlation with CDK10. IHC detected staining of CDK10 in tumors (a, i) and absent staining for CDK10 in tumors (a, ii); CDK10 was significantly correlated with C1orf63 in patients with breast cancer from datasets E-GEOD-4922 (b, i), E-GEOD-5847 (b, ii), E-GEOD-23988 (b, iii) and E-TABM-158 (b, iv). The Y-axis and X-axis respectively represented the mRNA expression of CDK10 and C1orf63 on the log-2 scale
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4513615&req=5

Fig5: C1orf63 expression in human breast tissues and its correlation with CDK10. IHC detected staining of CDK10 in tumors (a, i) and absent staining for CDK10 in tumors (a, ii); CDK10 was significantly correlated with C1orf63 in patients with breast cancer from datasets E-GEOD-4922 (b, i), E-GEOD-5847 (b, ii), E-GEOD-23988 (b, iii) and E-TABM-158 (b, iv). The Y-axis and X-axis respectively represented the mRNA expression of CDK10 and C1orf63 on the log-2 scale
Mentions: CDK10 has been shown to play a role in cellular progression as well as a known prognostic factor predicting better outcome for breast cancers. Given the suggested role of C1orf63 on cell cycle exit [8], and its capability to predict better prognosis for breast cancers (Fig. 3B and Table 8), we thus examined the relationship between C1orf63 and CDK10. We firstly took advantage of four publicly available microarray datasets, each including a cohort of patients with breast cancer, to evaluate whether mRNA expression of C1orf63 could be related to that of CDK10. As shown in Fig. 5B, for mRNA expression, C1orf63 was positively correlated with CDK10, and the RNA-seq dataset also displayed a significant correlation between these two genes (r = 0.521, P < 0.001; Table 2). Further, CDK10 protein expression was examined by IHC. As shown in Fig. 5Ai, CDK10 primarily expressed in the nucleus and the relationship between the IHC scores of CDK 10 and C1orf63 was consistent with that of their mRNA expressions, which demonstrated that C1orf63 expression was positively correlated with CDK10 (rs = 0.391; P < 0.001).Fig. 5

Bottom Line: Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145).Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001).In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.

View Article: PubMed Central - PubMed

Affiliation: Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China. chaoqunhong@gmail.com.

ABSTRACT

Background: Chromosome 1 open reading frame 63 (C1orf63) is located on the distal short arm of chromosome 1, whose allelic loss has been observed in several human cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T lymphocytes, which suggests it might be involved in cell cycle control, a common mechanism for carcinogenesis. Here we investigated the expression and clinical implication of C1orf63 in breast cancer.

Methods: Paraffin-embedded specimens, clinicopathological features and follow-up data of the breast cancer patients were collected. Publicly available microarray and RNA-seq datasets used in this study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool was also adopted. The expression of C1orf63 and CDK10, one known cell cycle-dependent tumor suppressor in breast cancer, was assessed by immunohistochemistry. Western blotting was performed to detect C1orf63 protein in human breast cancer cell lines, purchased from the Culture Collection of the Chinese Academy of Sciences, Shanghai.

Results: In a group of 12 human breast tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression both in breast cancer and several other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma. In another group of 182 breast cancer patients, C1orf63 expression in tumors was not correlated with any clinicopathological features collected in this study. Survival analyses showed that there was no significant difference of overall survival (OS) rates between the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145). However, the analyses of KM plotter displayed a valid relationship between C1orf63 and RFS (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression was an independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001).

Conclusions: Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10.

No MeSH data available.


Related in: MedlinePlus