Altered immunoexpression of DNA polymerase delta 1 catalytic subunit (POLD1) in colorectal cancer

结直肠癌中 DNA 聚合酶 delta 1 催化亚基 (POLD1) 的免疫表达改变

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作者:Przemysław Stefaniak, Bartłomiej Emil Kraziński, Jacek Kieżun, Hanna Majewska, Janusz Godlewski

Conclusions

Despite previous studies suggesting that POLD1 genetic alterations could be promising molecular biomarkers in CRC, our results do not support any prognostic significance of POLD1 expression in CRC.

Material and methods

Paired, tumour and non-cancerous tissue samples of the large intestine distant to the neoplasm were collected from the postoperative material of 78 patients who underwent surgical resection of CRC tumours. Polymerase delta 1 catalytic subunit protein levels were determined using immunohistochemistry. Clinical, pathomorphological, and survival data of the patients were pooled. In addition, POLD1 mRNA expression levels of 599 CRC patients were extracted from The Cancer Genome Atlas (TCGA) datasets and subjected to statistical and survival analysis including the Kaplan-Meier method followed by the log-rank test.

Methods

Paired, tumour and non-cancerous tissue samples of the large intestine distant to the neoplasm were collected from the postoperative material of 78 patients who underwent surgical resection of CRC tumours. Polymerase delta 1 catalytic subunit protein levels were determined using immunohistochemistry. Clinical, pathomorphological, and survival data of the patients were pooled. In addition, POLD1 mRNA expression levels of 599 CRC patients were extracted from The Cancer Genome Atlas (TCGA) datasets and subjected to statistical and survival analysis including the Kaplan-Meier method followed by the log-rank test.

Results

Immunoexpression of POLD1 was found in the nuclei of the tumour cells and epithelial cells of unchanged intestinal mucosa. Polymerase delta 1 catalytic subunit immunoreactivity in the tumour was heterogenous, and the average immunoreactivity score was decreased in cancer cells when compared to the mucosa of matched sections of unchanged large intestine (p = 0.0259). However, POLD1 expression at the protein and mRNA levels did not associate with clinicopathological characteristics of the patients and their survival. Conclusions: Despite previous studies suggesting that POLD1 genetic alterations could be promising molecular biomarkers in CRC, our results do not support any prognostic significance of POLD1 expression in CRC.

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