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. 2023 Sep-Oct;20(5):487-499.
doi: 10.21873/cgp.20400.

Identification of Biomarkers Related to the Efficacy of Radiotherapy in Pancreatic Cancer

Gabriel Henrique Caxali  1 , Laíza Brugnerotto  1 , Mirian Carolini Esgoti Aal  1 , Camila Ferreira Bannwart Castro  2 , Flávia Karina Delella  3
Affiliations

Identification of Biomarkers Related to the Efficacy of Radiotherapy in Pancreatic Cancer

Gabriel Henrique Caxali et al. Cancer Genomics Proteomics. 2023 Sep-Oct.

Abstract

Background/aim: Pancreatic cancer (PC) has one of the highest mortality rates, with an overall five-year survival rate of only 7%. When diagnosed, PC is limited to the pancreas in only 20% of patients, whereas in 50% it has already metastasized. This is due to its late diagnosis, which makes the treatments used, such as radiotherapy, difficult, and reduces survival rates. Therefore, the importance of this study in detecting genes that may become possible biomarkers for this type of tumor, especially regarding the human secretome, is highlighted. These genes participate in pathways that are responsible for tumor migration and resistance to therapies, along with other important factors.

Materials and methods: To achieve these goals, the following online tools and platforms have been expanded to discover and validate these biomarkers: The Human Protein Atlas database, the Xena Browser platform, Gene Expression Omnibus, the EnrichR platform and the Kaplan-Meier Plotter platform.

Results: Our study adopted a methodology that allows the identification of potential biomarkers related to the effectiveness of radiotherapy in PC. Inflammatory pathways were predominantly enriched, related to the regulation of biological processes, primarily in cytokine-derived proteins, which are responsible for tumor progression and other processes that contribute to the development of the disease.

Conclusion: Radiotherapy treatment demonstrated greater efficacy when used in conjunction with other forms of therapy since it decreased the expression of essential genes involved in several inflammatory pathways linked to tumor progression.

Keywords: Pancreatic cancer; bioinformatics; biomarker; radiotherapy; resistance; secretome.

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Conflict of interest statement

The Authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Differentially expressed genes comparing normal tissue samples from GTEx database and PC tumor tissue samples from TCGA database, using the EdgeR analysis from Appyters tool. Down-regulated genes are shown in blue, up-regulated genes in red and non-significant genes are shown in gray.
Figure 2
Figure 2. Volcano plot of the expression of significant genes present in four groups of comparisons in the study GSE129492 using the GEO2R tool. (A) Chemotherapy versus chemotherapy followed by conventional radiotherapy (XRT); (B) chemotherapy versus chemotherapy followed by stereotactic body radiation therapy (SBRT); (C) surgical resection (control) versus chemotherapy followed by XRT; (D) surgical resection (control) versus chemotherapy followed by SBRT. Note the greater number of down-regulated genes (in blue) compared to the up-regulated genes (in red).
Figure 3
Figure 3. Volcano plot of the expression of significant genes present in the groups of patients treated and not treated with SBRT in GSE 185311 using the GEO2R tool. Our study identified 3 up-regulated genes (GDF15, CDKN1A and CRP) and 2 down-regulated genes (CCL21 and TNFRSF13C).
Figure 4
Figure 4. Enrichment graph of the 7 down-regulated genes identified (IFNG, IL1A, IL12B, IL26, LAIR2, SEMG1 and XCL2), from ontology databases. (A) GO: BIOLOGICAL PROCESS, GO: MOLECULAR FUNCTION and pathways databases; (B) REACTOME 2021 and NCI-NATURE 2021 databases.
Figure 5
Figure 5. Survival curves generated from the identified potential biomarkers: IFNG (A), IL1A (B), IL12B (C), SEMG1 (D). Survival curves were generated with the KMPlotter tool.
Figure 6
Figure 6. Immunohistochemical validation of IFNG (A), and IL12B (B), in normal and tumoral pancreatic tissue from the database “The Human Protein Atlas”.
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