The Mrna Expression Level Of Olq In Human Pan-cancer
The expression of POLQ mRNA in normal tissue was firstly analyzed using the GTEx database. The result showed that POLQ expression was highest in the Bone Marrow and Testis tissue, and was lowest in Fallopian Tube and Pituitary tissue (Fig. 1A). Expression analyses of POLQ tumor cell lines showed that POLQ was expressed in all 21 kinds of tumor cell lines (Supplentary Fig. 1A). Then, the differences in POLQ expression between tumor and normal tissues was assessed by using TCGA database. As illustrated in Supplentary Fig. 1B, POLQ expression was significantly upregulated in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), rectum adenocarcinoma(READ), stomach adenocarcinoma (STAD) and uterine corpus endometrial carcinoma (UCEC) tissues than in normal tissues. For the tumors lacking enough normal tissue samples in TCGA database, the corresponding normal tissue data from the GTEx database was used to analyze the differences in POLQ expression. The results showed that POLQ expression was upregulated in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), testicular germ cell tumors (TGCT), thyroid carcinoma (THCA), uterine carcinosarcoma (UCS), acute myeloid leukemia (LAML), BLCA, BRCA, CHOL, COAD, ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUAD, LUSC, PRAD, READ, STAD, skin cutaneous melanoma (SKCM) and UCEC than in the normal tissues (Fig. 1B). In summary, these results revealed that POLQ is abnormally expressed in multiple cancers and suggested a potential role of POLQ in tumor progression.
Prognostic Value Of Polq In Human Pan-cancer
The prognostic value of POLQ expression was analyzed by investigating the relationship between POLQ expression and characteristics of OS, DSS, DFI and PFI. Higher POLQ expression was associated with shorter OS and 5-year OS (HR > 1) in ACC, KICH, KIRC, KIRP, LGG, LIHC, mesothelioma (MESO), PAAD and UCEC, but longer OS and 5-year OS (HR < 1) in thymoma (THYM). (Fig. 2A, Table 1, Supplementary Fig. 2A). DSS analysis was performed and found similar results (Fig. 2B, Supplementary Fig. 2B). DFI analysis found that upregulation of POLQ expression was correlated with poor prognosis in UCEC, THCA, sarcoma (SARC), PAAD, KIRP and LIHC (Supplementary Fig. 2C, Supplementary Fig. 3A). PFI analysis found that increased POLQ expression was associated with poor outcome in ACC, KICH, KIRC, KIRP, LGG, PCPG, LIHC, LUAD, MESO, PAAD, PRAD, SARC, THCA, and UCEC (Supplementary Fig. 2D, Supplementary Fig. 3B). Taken together, these results suggested that the upregulation of POLQ is significantly correlated with the prognosis of patients, especially in UCEC, KIRP, and LIHC.
Correlation Between Polq Expression And Tumor Immune Microenvironment
Immune cell in the tumor immune microenvironment affect the survival of patients[40]. The association between POLQ expression and immune cell infiltration in human pan-cancer was analyzed using TIMER. A appreciably positive correlation between the expression of POLQ and the infiltration levels of B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells was observed in KIRC, LGG, LIHC, PRAD, THCA. In UVM, a positive correlation was observed in B cells, CD8 + T cells and neutrophils, and a negative correlation was observed in CD4 + T cells, macrophages and dendritic cells (Fig. 6). Then, we used the immune score, matrix score and ESTIMATE Score to investigate the correlation between POLQ expression and TIME. A strong positive correlation was observed in immune scores in KIRC and THCA (Fig. 7A), and stromal scores (Fig. 7B) as well as ESTIMATE scores (Supplementary Fig. 5A) in PRAD, KIRC and THCA. Immune checkpoint inhibitors (ICIs) as novel tumor immunotherapy agents, act an significant role in tumor immunotherapy[41]. Subsequently, the correlation between POLQ expression and the expression of 47 common immune checkpoint genes was also analyzed. Interestingly, POLQ expression was correlated with more than 30 immune checkpoint markers in KIRC and THCA, such as CTLA4, CD48, and CD28 (Supplementary Fig. 5B). In conclusion, these results strongly suggest that POLQ plays an important role in tumor immunity.
Gene set enrichment analysis (GSCA) and pathway exploration for POLQ in pan-cancer based on different databases
Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway Enrichment analysis, we found that POLQ is associated with the “Cell cycle”, “cell cycle checkpoint”, “DNA replication”,“double-strand break repair”,“Fanconi anemia pathway”,“Homologous recombination”,“DNA replication” and so on (Fig. 8A, B). Moreover, we used GSCA database to analyze the role of POLQ in cancer-related pathways in pan-cancer. The global percentage indicated that POLQ had a complete activation of apoptosis, cell cycle, DNA damage response, and a complete inhibitory effect of RAS/MAPK and Hormone ER (Fig. 8C).
Polq Expression And Drug Sensitivity Analysis
Study found that the expression of POLQ was associated with the anti-cancer drugs sensitivity. And we analyzed RNAactDrug database to determine the association between the anti-cancer drugs sensitivity and POLQ mRNA at multiomics level. As shown in Table 2, Belinostat, Foretinib, Cabozantinib, Gefitinib, Olaparib, Vinorelbine were negatively correlated with POLQ mRNA expression; Alectinib, Amuvatinib, Belinostat, Cisplatin, Dabrafenib, Daporinad, Lenalidomide, Linifanib, Masitinib, Olaparib, Ponatinib, Quizartinib, Selisistat, Tamoxifen, Tretinoin, Tubastatin A, Vorinostat were positively correlated with POLQ CNV. And study found that POLQ plays a crucial role in BRCA1/2-deficient cancers and POLQ can weak the effect of PARP inhibitors[42]. For example, depletion of POLQ can reduce the survival of HRD cells exposed to PARP inhibitors, cisplatin or mitomycin, making POLQ as a potential therapeutic target in breast and ovarian cancers with BRCA1/2-deficiency and other HR deficiencies[20]. And the data of GDSC and CTRP databases (Fig. 9) as well as Table 2 indicated that POLQ is associated with drug sensitivity.