Original StudyHigh Expression of Long Noncoding RNA MALAT1 Indicates a Poor Prognosis and Promotes Clinical Progression and Metastasis in Bladder Cancer
Introduction
Bladder cancer (BC) arises from the urothelium of the urinary bladder. Currently, as the second most common malignancy of the urinary system after prostate cancer, BC has an enormously high incidence, with more than 76,000 new cases each year in the United States.1 Most patients are approximately 50 to 70 years of age, and the incidence in men is approximately 3.3 times that of women.2 BC can be divided into 2 types: non–muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). These 2 types show differences, such as abilities to invade, recur, and metastasize. Most new patients diagnosed with NMIBC receive surgical resection followed by bladder instillation treatment; of them, more than a half will relapse within 5 years and may upgrade to MIBC, which is highly aggressive, with a poor prognosis, and a 5-year survival rate of less than 50%.3 Therefore, it is of great importance to reveal the molecular mechanism of the development of BC, and to seek reliable biomarkers as effective therapeutic targets to improve the survival of the patients.
Whole-genome studies found that the encoding function gene of DNA accounts for only 2% of the whole genome, whereas noncoding DNA represents most of the genome. Noncoding RNA is the product of noncoding DNA transcription. According to the length of the sequence, noncoding RNA can be divided into 3 types: long-chain, medium-chain, and short-chain noncoding RNA. Long-chain noncoding RNA (lncRNA) refers those with a chain longer than 200 nt.4 In the past, lncRNA was considered only as the “noise” of gene transcription, and was paid little attention,5 but recent studies found that lncRNA has a number of functions in various human biological processes, including transcription interference, gene splicing, transcription regulation, genomic imprinting, X-chromosome inactivation, cell-cycle regulation, dyeing modification, apparent genetic modification, and immune response.6
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is located on chromosome 11q13.1, with a full length of 8.7 kb. In 2003, Ji et al7 first reported that the expression of MALAT1 was elevated in cancer cells from patients with non–small-cell lung cancer. Recent studies confirmed that the expression of MALAT1 promotes cancer cell proliferation, invasion, and metastasis in breast cancer, pancreatic cancer, colon cancer, liver cancer, and lung cancer, but the association between BC and MALAT1 remains unclear.8, 9, 10, 11, 12
Therefore, the aim of the present study was to investigate the biological and clinical function of MALAT1 in BC, and to verify whether MALAT1 could be used as a therapeutic target for BC and a biomarker to determine preoperative presence of progression and lymph node metastasis.
Section snippets
Specimens
BC specimens (n = 120) were obtained from consecutive patients operated at the Xiangya Hospital between January 2008 and December 2012. All the patients were treated by surgery, including transurethral resection of bladder tumor and radical resection of the bladder. The tumor specimens were staged according to the 2009 seventh version of the Union International Contre le Cancer TNM staging system, and graded according to the 2004 World Health Organization classification. All patients were
Expression Intensity of MALAT1 in BC
The expression intensity of MALAT1 was classified as negative, weakly positive, moderately positive, and strongly positive (scored 1 to 4, respectively). Samples were tested in quadruplicate; 2 doctors examined the slides in a double-blind manner to determine the staining intensity of each specimen. The average value was taken as the corresponding MALAT1 expression intensity.
Among the 120 specimens, the results showed that MALAT1 expression was negative in 24 cases, weakly positive in 32,
Discussion
Accumulating evidence suggests the importance of lncRNA MALAT1 in various human cancers,8, 9, 10, 11, 12 but the associations between MALAT1 and a mechanistic role in driving BC, especially lymph node metastasis, was unclear. In the present study, ISH was used to detect the expression of MALAT1 in paraffin BC sections, and the relationship between MALAT1 expression and clinical progression, lymph node metastasis, and prognosis of BC were retrospectively analyzed. qRT-PCR was used to detect the
Conclusion
This study examined the underlying association between MALAT1 and BC from the pathogenic aspect. Elevated expression of MALAT1 could be involved in the progression and metastasis of BC, and could therefore be considered as a prognostic factor for patients with BC. With better understanding of the potential pathogenic mechanism of BC, MALAT1 could serve as a new biomarker and potential molecular therapeutic target for estimating tumor progression and lymph node metastasis of BC.
Disclosure
The authors declare that they have no conflicts of interests.
Acknowledgments
Funding for this work was provided by the Hunan Province Funds for Distinguished Young Scientists of China (2016JJ1026).
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