Dataset Information

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.

ABSTRACT:

Background

The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ ) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa patients and analyzed associations between the expression and disease outcome.

Methods

The expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3⁷⁰⁵ was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99).

Results

The nuclear expression levels of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3⁷⁰⁵ in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmö cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values.

Conclusions

Low pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.

SUBMITTER: Krzyzanowska A

PROVIDER: S-EPMC6766958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Signal transducer and activator of transcription 3 (Stat3) is responsible for many aspects of normal development and contributes to the development and progression of cancer through regulating epithelial cell identity and cancer stem cells. In breast cancer, Stat3 is associated with triple-negative breast cancers (TNBC) and its function has been related to the activation of p63, itself a marker of basal-like TNBC and a master regulator of stem cell activities. Stat3 activation is controlled by dual phosphorylation at tyrosine 705 (pTyr705) and serine 727 (pSer727), although it is unclear whether these have equivalent effects, and whether they are related or independent events. To address these issues, we investigated Stat3 phosphorylation at the two sites by immunohistochemistry in 173 patients with TNBC. Stat3 phosphorylation was assessed by automated quantitative measurements of digitized scanned images and classified into four categories based on histoscore. The results were analyzed for associations with multiple markers of tumor phenotype, proliferation, BRCA status, and clinicopathological characteristics. We show that the levels of pTyr705- and pSer727-Stat3 were independent in 34% of tumors. High pTyr705-Stat3 levels were associated with the luminal differentiation markers ERβ/AR and MUC1, whereas tumors with high levels of pSer727-Stat3 were more likely to be positive for the basal marker CK5/6, but were independent of p63 and were EGFR negative. Combined high pSer727- and low Tyr705-Stat3 phosphorylation associated with basal-like cancer. Although high Stat3 phosphorylation levels were associated with less aggressive tumor characteristics, they did not associate with improved survival, indicating that Stat3 phosphorylation is an unfavorable indicator for tumors with an otherwise good prognosis according to clinicopathological characteristics. These findings also show that pTyr705-Stat3 and pSer727-Stat3 associate with specific breast tumor phenotypes, implying that they exert distinct functional activities in breast cancer.

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Dataset Information

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.

Background

Methods

Results

Conclusions

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Dataset Information

Expression of tSTAT3, pSTAT3727 , and pSTAT3 705 in the epithelial cells of hormone-naive prostate cancer.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.