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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 cases and controls of several cancers .a IHC detected strong staining of C1orf63 in breast tumors (i, original magnification 400×), moderate staining of C1orf63 in breast tumors (ii, 400×), weak staining of C1orf63 in breast tumors (iii, 400×) and absent staining of C1orf63 in adjacent normal tissues (iv, 400×); b C1orf63 mRNA expression was significantly higher in cases than that in controls of several cancer, namely breast cancer (i, GSE15852; ii, GSE42568), lung cancer (iii, E-MEXP-231; iv, GSE19804), prostate cancer (v, GSE6956; vi, GSE6919) and hepatocellular carcinoma (vii, GSE14323; viii, GSE6764). P values were derived from student t-test
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Fig1: C1orf63 expression in cases and controls of several cancers .a IHC detected strong staining of C1orf63 in breast tumors (i, original magnification 400×), moderate staining of C1orf63 in breast tumors (ii, 400×), weak staining of C1orf63 in breast tumors (iii, 400×) and absent staining of C1orf63 in adjacent normal tissues (iv, 400×); b C1orf63 mRNA expression was significantly higher in cases than that in controls of several cancer, namely breast cancer (i, GSE15852; ii, GSE42568), lung cancer (iii, E-MEXP-231; iv, GSE19804), prostate cancer (v, GSE6956; vi, GSE6919) and hepatocellular carcinoma (vii, GSE14323; viii, GSE6764). P values were derived from student t-test

Mentions: The tumor specimens and their matched adjacent non-cancerous tissues were collected from a group of 12 breast cancer patients to examine C1orf63 expression by IHC. As shown in Fig. 1A (i, ii, iii), C1orf63 protein was expressed primarily in the cytoplasm. We found 7 of the 12 primary tumors (58.3 %) expressed C1orf63 (Table 4), whereas 5 of the 12 tumors (41.7 %) had indistinctive expression of C1orf63. In contrast, all the adjacent normal tissues lacked elevated C1orf63 expression (Wilcoxon test: P < 0.001, Fig. 1A iv). Additionally, though analyzing the publicly available datasets, upregulation of C1orf63 mRNA expression was found in cases of breast cancer as well as other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma (Table 3 and Fig. 1B), when compared to the relevant normal controls.Fig. 1


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 cases and controls of several cancers .a IHC detected strong staining of C1orf63 in breast tumors (i, original magnification 400×), moderate staining of C1orf63 in breast tumors (ii, 400×), weak staining of C1orf63 in breast tumors (iii, 400×) and absent staining of C1orf63 in adjacent normal tissues (iv, 400×); b C1orf63 mRNA expression was significantly higher in cases than that in controls of several cancer, namely breast cancer (i, GSE15852; ii, GSE42568), lung cancer (iii, E-MEXP-231; iv, GSE19804), prostate cancer (v, GSE6956; vi, GSE6919) and hepatocellular carcinoma (vii, GSE14323; viii, GSE6764). P values were derived from student t-test
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: C1orf63 expression in cases and controls of several cancers .a IHC detected strong staining of C1orf63 in breast tumors (i, original magnification 400×), moderate staining of C1orf63 in breast tumors (ii, 400×), weak staining of C1orf63 in breast tumors (iii, 400×) and absent staining of C1orf63 in adjacent normal tissues (iv, 400×); b C1orf63 mRNA expression was significantly higher in cases than that in controls of several cancer, namely breast cancer (i, GSE15852; ii, GSE42568), lung cancer (iii, E-MEXP-231; iv, GSE19804), prostate cancer (v, GSE6956; vi, GSE6919) and hepatocellular carcinoma (vii, GSE14323; viii, GSE6764). P values were derived from student t-test
Mentions: The tumor specimens and their matched adjacent non-cancerous tissues were collected from a group of 12 breast cancer patients to examine C1orf63 expression by IHC. As shown in Fig. 1A (i, ii, iii), C1orf63 protein was expressed primarily in the cytoplasm. We found 7 of the 12 primary tumors (58.3 %) expressed C1orf63 (Table 4), whereas 5 of the 12 tumors (41.7 %) had indistinctive expression of C1orf63. In contrast, all the adjacent normal tissues lacked elevated C1orf63 expression (Wilcoxon test: P < 0.001, Fig. 1A iv). Additionally, though analyzing the publicly available datasets, upregulation of C1orf63 mRNA expression was found in cases of breast cancer as well as other cancers, including lung cancer, prostate cancer and hepatocellular carcinoma (Table 3 and Fig. 1B), when compared to the relevant normal controls.Fig. 1

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