Prognostic significance of long noncoding RNA Z38 as a candidate biomarker in breast cancer

Abstract

Background: Long noncoding RNA (lncRNA) Z38 has been shown to promote cell proliferation and tumorigenesis in breast cancer. However, expression pattern and prognostic value of lncRNA Z38 in breast cancer patients remain elusive.

Methods: The expression levels of SPRY4-IT1 in 110 self-paired specimens of breast cancer and adjacent normal breast tissues were measured by quantitative real-time PCR (qRT-PCR), and its correlation with overall survival of patients with breast cancer was further statistically analyzed.

Results: Compared with normal breast tissues, Z38 was upregulated in breast cancer tissues. Furthermore, of 110 breast cancer patients, high Z38 expression was significantly associated with tumor-node-metastasis stage and lymph node metastasis. Further analysis using the Cox regression model revealed that Z38 expression was an independent prognostic factor of overall survival in patients with breast cancer (hazard ratio=4.74, 95% confidence interval 2.41-9.32). The nomogram presents a good prediction of the probability of overall survival of breast cancer patients (c-index: 0.792), and its predictive efficiency was further confirmed by the calibration curve.

Conclusion: Our data highlighted the potential of lncRNA Z38 as novel candidate biomarker to identify patients with breast cancer at high risk of tumor death.

Keywords: Z38; breast cancer; long noncoding RNA; prognosis.

Figure 1

Relative levels of Z38 in breast cancer tissues samples. quantitative real‐time PCR analyses to determine the relative levels of Z38 in a total of 110 breast cancer patients, a paired Wilcoxon signed‐rank test was performed, *** indicate P <.001.

Figure 2

Optimal cutoff value of Z38 expression determined by receiver operating characteristic curve for overall survival.

Figure 3

Survival analysis in breast cancer patients based on Z38 expression. Overall survival based on high Z38 expression versus low Z38 expression in patients with breast cancer.

Figure 4

Nomogram conveyed significant clinical characteristics and Z38 expression to predict overall survival of breast cancer patients. Nomogram is interpreted by summing up the points assigned to each factor, which is indicated at the top of scale. The total points can be converted to predicted 3‐y and 5‐y probability of death for a patient in the lowest scale. The Harrell's c‐indexes for overall survival prediction were 0.792. TNM, tumor‐node‐metastasis.

Figure 5

Calibration curve for 5‐y overall survival. The x‐axis is its predicted probability of 5‐y survival and y‐axis is actual survival. The dashed line is 45 degree and presents perfect calibration.