In Silico Analysis to Determine the Association of Specificity Protein (Sp) Transcription Factors, Sp1 and Sp3 and Survivin Expression with the Prognosis of Cancers Affecting Women

Date

2023

Authors

Patel, Pooja
Dutta, Arpam

ORCID

0000-0002-0275-5621 (Patel, Pooja)
0000-0001-9808-0579 (Dutta, Arpam)

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Abstract

Background: Breast cancer is the most common invasive cancer in women worldwide. Studies have shown that breast cancer shares risk factors and genetic mutations with ovarian and uterine cancers which are also analyzed to be increasing in incidence. Clinically, diagnosis of concurrent genetically shared cancers like breast, ovarian, and uterine would have an impact on the treatment options and its course. Dysregulation of transcription factors like Specificity protein (Sp) 1 and 3 which remodel chromatin is responsible for many cancers. While the expression of Sp1 is documented to be upregulated in breast and ovarian cancer, and Sp3 only in breast; uterine cancer lacks such evidence. Baculoviral IAP repeat-containing 5 (BIRC5), also known as survivin, is an inhibitor of the apoptotic pathway and is found to be upregulated in breast, ovarian, and uterine cancer. Sp1, Sp3 and survivin are all associated with high expression in numerous cancers and lead to poor prognosis.

Objective: The objective of this study is to analyze the expression of Sp1, Sp3 and survivin in breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma to evaluate the prognosis (in all patients and by race/ethnicity) of cancer patients using the data deposited in a public database.

Methods: Relevant data and Kaplain-Meier curves were obtained from accessing the public database, The Cancer Genome Atlas (TCGA) (a landmark cancer genomics program developed by the National Cancer Institute and the National Human Genome Research Institute). This data was used to screen for the expression status (upregulated or downregulated), significance and relevance to prognosis for all patients and in relation to race/ethnicity for breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma.

Results: Sp1, Sp3, and survivin expression significantly impacted patient survival in breast invasive carcinoma (n=1211), ovarian serous cystadenocarcinoma (n=302), and uterine corpus endometrial carcinoma (n=581). When looking at Sp1 and combining data for all patients, there was a relevance in prognosis in ovarian serous cystadenocarcinoma (p=0.045). Additionally, there was an association between the marker and poor prognosis for race/ethnicity when looking at breast invasive carcinoma and uterine corpus endometrial carcinoma. Sp3 and survivin presented similarly when looking at combined and racial/ ethnic prognosis. Both Sp3 and survivin indicated a poorer prognosis for overall population survival in uterine corpus endometrial carcinoma (p=0.018 and p=0.015 respectively). They also presented with a worse prognosis when looking at race/ethnicity for all three listed cancers.

Conclusion: The findings from this study suggest an association of Sp1, Sp3, and survivin expression in breast invasive carcinoma, ovarian serous cystadenocarcinoma, and uterine corpus endometrial carcinoma and their prognosis. The results also suggest that these markers may contribute to poor prognosis for patients in certain racial/ethnic groups.

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