The lncRNA SCHLAP1 predicts poor prognosis in multifocal primary prostate cancer
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Expression of SCHLAP1 is heterogeneous within and between different malignant foci
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Multiple samples per patient is crucial, otherwise high SCHLAP1 may be overlooked
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High SCHLAP1 is associated with reactive stroma and other aggressive features
Abstract
In primary prostate cancer, the common multifocality and heterogeneity are major obstacles in finding robust prognostic tissue biomarkers. The long noncoding RNA SCHLAP1 has been suggested, but its prognostic value has not been investigated in the context of tumor heterogeneity. In the present study, expression of SCHLAP1 was investigated using real-time RT-PCR in a multisampled series of 778 tissue samples from radical prostatectomies of 164 prostate cancer patients (median follow-up time 7.4 y). The prognostic value of SCHLAP1 was evaluated with biochemical recurrence as endpoint.
In total, 29% of patients were classified as having high expression of SCHLAP1 in at least one malignant sample. Among these, inter- and intrafocal heterogeneity was detected in 72% and 56%, respectively. High expression of SCHLAP1 was shown to be a predictor of biochemical recurrence in both uni- and multivariable cox regression analyses (P < 0.001 and P = 0.02). High expression of SCHLAP1 was also significantly associated with adverse clinicopathological characteristics, including grade group, high pT stage, invasive cribriform growth/intraductal carcinoma of the prostate, and reactive stroma. In conclusion, high expression of SCHLAP1 in at least one malignant sample is a robust prognostic biomarker in primary prostate cancer. For the first time, high SCHLAP1 expression has been associated with the aggressive histopathologic feature reactive stroma. The expression of SCHLAP1 is highly heterogeneous, and analysis of multiple samples is therefore crucial in determination of the SCHLAP1 status of a patient.
Keywords
Biomarker
Heterogeneity
lncRNA
Multifocality
Prognosis
Prostate cancer
Abbreviations
BCR
biochemical recurrence
IDCP
intraductal carcinoma of the prostate
lncRNA
long noncoding RNA
PSA
prostate-specific antigen
pT stage
pathological tumor stage
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Funding: The study was supported by the South-Eastern Norway Regional Health Authority (SGK, KTC and MB were financed as PhD students from grants with project numbers 2020063, 2017045, and 2019016), the Research Council of Norway through its FRIPRO funding scheme (262529/F20 and Toppforsk-250993), and the Norwegian Cancer Society (grant number 208197). The study was granted secure storage of computer files and high-performance computation resources from NorStore and University of Oslo's Services for Sensitive Data (NS9013S and p19, respectively).
Conflicts of interest: The authors declare no potential conflicts of interest.