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. 2022 Sep 8;13(9):1611.
doi: 10.3390/genes13091611.

Endometrial Cancer-Adjacent Tissues Express Higher Levels of Cancer-Promoting Genes than the Matched Tumors

Mariusz Kulinczak  1 , Maria Sromek  1 , Grzegorz Panek  2 , Klara Zakrzewska  3 , Renata Lotocka  4 , Lukasz Michal Szafron  1 , Magdalena Chechlinska  1 , Jan Konrad Siwicki  1
Affiliations

Endometrial Cancer-Adjacent Tissues Express Higher Levels of Cancer-Promoting Genes than the Matched Tumors

Mariusz Kulinczak et al. Genes (Basel). .

Abstract

Molecular alterations in tumor-adjacent tissues have recently been recognized in some types of cancer. This phenomenon has not been studied in endometrial cancer. We aimed to analyze the expression of genes associated with cancer progression and metabolism in primary endometrial cancer samples and the matched tumor-adjacent tissues and in the samples of endometria from cancer-free patients with uterine leiomyomas. Paired samples of tumor-adjacent tissues and primary tumors from 49 patients with endometrial cancer (EC), samples of endometrium from 25 patients with leiomyomas of the uterus, and 4 endometrial cancer cell lines were examined by the RT-qPCR, for MYC, NR5A2, CXCR2, HMGA2, LIN28A, OCT4A, OCT4B, OCT4B1, TWIST1, STK11, SNAI1, and miR-205-5p expression. The expression levels of MYC, NR5A2, SNAI1, TWIST1, and STK11 were significantly higher in tumor-adjacent tissues than in the matched EC samples, and this difference was not influenced by the content of cancer cells in cancer-adjacent tissues. The expression of MYC, NR5A2, and SNAI1 was also higher in EC-adjacent tissues than in samples from cancer-free patients. In addition, the expression of MYC and CXCR2 in the tumor related to non-endometrioid adenocarcinoma and reduced the risk of recurrence, respectively, and higher NR5A2 expression in tumor-adjacent tissue increased the risk of death. In conclusion, tissues proximal to EC present higher levels of some cancer-promoting genes than the matched tumors. Malignant tumor-adjacent tissues carry a diagnostic potential and emerge as new promising target of anticancer therapy.

Keywords: cancer-promoting genes; endometrial carcinoma; field cancerization; tumor-adjacent tissues.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The studied samples from endometrial cancer (a,b) and cancer-free leiomyoma cases (c); a, paired tumor (T, red) and cancer cell-free tumor-adjacent samples (TA, blue); b, paired samples of tumors (Tc, red) and tumor-adjacent samples containing cancer cells (TAc, blue and red); c, control tissues, endometrial samples from cancer-free patients with leiomyomas (Control, Ctrl, green).
Figure 2
Figure 2
MYC, NR5A2, TWIST1, and SNAI1 expression levels in tumors (T, red) and tumor-adjacent tissues without (TA, blue) or with (TAc, blue-dashed) cancer cell content in patients with EC, and in endometrial tissue in cancer-free patients with leiomyoma (Control, green).
Figure 3
Figure 3
STK11, CXCR2, HMGA2, and LIN28A expression levels in tumors (T, red) and tumor-adjacent tissues without (TA, blue) or with (TAc, blue-dashed) cancer cell content in patients with EC, and in tumor-adjacent tissues in cancer-free patients with leiomyoma (Control, green).
Figure 4
Figure 4
POU5F1 (isoforms A, B, B1) and miR-205-5p expression levels in tumors (T, red) and tumor-adjacent tissues without (TA, blue) or with (TAc, blue-dashed) cancer cell content in patients with EC, and in endometrial tissue in cancer-free patients with leiomyoma (Control, green).
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Grants and funding

Cell lines were funded by Polish Foundation of the European School of Oncology (PFESO), otherwise this research received no external funding.