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High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer.

ABSTRACT: Pseudogenes play pivotal roles in tumorigenesis. Previous studies have suggested that pituitary tumor-transforming 3, pseudogene (PTTG3P), serves as an oncogene in human cancers. However, its expression pattern, biological function, and underlying mechanism in breast cancer remain unknown. In this study, we demonstrated an elevated expression of PTTG3P in breast cancer and discovered that PTTG3P expression correlated negatively with estrogen receptor (ER) and progesterone receptor (PR) status, but linked positively to basal-like status, triple-negative breast cancer status, Nottingham prognostic index (NPI), and Scarff-Bloom-Richardson grade. High expression of PTTG3P was also found to be associated with a poor prognosis of breast cancer. To explore the potential mechanisms of PTTG3P, a PTTG3P-microRNA (miRNA)-mRNA regulatory network was established. Co-expressed genes of PTTG3P were also obtained. Enrichment analysis for these co-expressed genes revealed that they were significantly enriched in mitotic nuclear division and cell cycle. Subsequent research on mechanism of PTTG3P indicated that its expression correlated positively with PTTG1 expression. However, no significant expression correlation between PTTG3P and PTTG2 was observed. Taken together, our findings suggest that increased expression of pseudogene PTTG3P may be used as a promising prognostic biomarker and novel therapeutic target for breast cancer.

SUBMITTER: Lou W

PROVIDER: S-EPMC6463746 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer.

Lou Weiyang W Ding Bisha B Fan Weimin W

Molecular therapy oncolytics 20190327

Pseudogenes play pivotal roles in tumorigenesis. Previous studies have suggested that pituitary tumor-transforming 3, pseudogene (PTTG3P), serves as an oncogene in human cancers. However, its expression pattern, biological function<b>,</b> and underlying mechanism in breast cancer remain unknown. In this study, we demonstrated an elevated expression of PTTG3P in breast cancer and discovered that PTTG3P expression correlated negatively with estrogen receptor (ER) and progesterone receptor (PR) st ...[more]

PMID: 31011629

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Project description:KLK14 (formerly known as KLK-L6) is a recently identified member of the human kallikrein gene family. This family harbours several genes aberrantly expressed in various cancers as well as established (PSA/hK3, hK2) and potential (hK6, hK10) cancer markers. Similar to other kallikrein genes, KLK14 was found to be regulated by steroid hormones, particularly androgens and progestins, in breast and ovarian cancer cell lines. Preliminary studies indicated that KLK14 is differentially expressed in breast, ovarian, prostatic and testicular tumours. Given the above, we determined the prognostic significance of KLK14 expression in breast cancer. We studied KLK14 expression in 178 histologically confirmed epithelial breast carcinomas by quantitative reverse transcription-polymerase chain reaction and correlated with clinicopathological variables (tumour stage, grade, histotype etc.) and with outcome (disease-free survival and overall survival), monitored over a median of 76 months. KLK14 mRNA levels ranged from 0 to 1,219 arbitrary units in breast cancer tissues, with a mean+/-s.e. of 136+/-22. An optimal cutoff value of 40.5 arbitrary units was selected, to categorise tumours as KLK14-positive or negative. Higher concentrations of KLK14 mRNA were more frequently found in patients with advanced stage (III) disease (P=0.032). No statistically significant association was found between KLK14 and the other clinicopathological variables. KLK14 overexpression was found to be a significant predictor of decreased disease-free survival (hazard ratio of 2.31, P=0.001) and overall survival (hazard ratio of 2.21, P=0.005). Cox multivariate analysis indicated that KLK14 was an independent prognostic indicator of disease-free survival and overall survival. KLK14 also has independent prognostic value in subgroups of patients with a tumour size </=2 cm and positive nodal, oestrogen receptor and progestin receptor status. We conclude that KLK14 expression, as assessed by quantitative reverse transcription-polymerase chain reaction, is an independent marker of unfavourable prognosis for breast cancer.

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High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer.

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High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer.

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