KIAA0101 as a new diagnostic and prognostic marker, and its correlation with gene regulatory networks and immune infiltrates in lung adenocarcinoma

Abstract

Proliferating cell nuclear antigen binding factor (encoded by KIAA0101/PCLAF) regulates DNA synthesis and cell cycle progression; however, whether the level of KIAA0101 mRNA in lung adenocarcinoma is related to prognosis and tumor immune infiltration is unknown. In patients with lung adenocarcinoma, the differential expression of KIAA0101 was analyzed using the Oncomine, GEPIA, and Ualcan databases. The prognosis of patients with different KIAA0101 expression levels was evaluated using databases such as Prognostan and GEPIA. Tumor immune infiltration associated with KIAA0101 was analyzed using TISIDB. Linkedmics was used to perform gene set enrichment analysis of KIAA0101. KIAA0101 expression in lung adenocarcinoma tissues was higher than that in normal lung tissues. Patients with lung adenocarcinoma with low KIAA0101 expression had a better prognosis than those with high KIAA0101 expression. We constructed the gene regulatory network of KIAA0101 in lung adenocarcinoma. KIAA0101 appeared to play an important role in the regulation of tumor immune infiltration and targeted therapy in lung adenocarcinoma. Thus, KIAA0101 mRNA levels correlated with the diagnosis, prognosis, immune infiltration, and targeted therapy in lung adenocarcinoma. These results provide new directions to develop diagnostic criteria, prognostic evaluation, immunotherapy, and targeted therapy for lung adenocarcinoma.

Keywords: KIAA0101/PCLAF; LUAD; biomarker; lung adenocarcinoma; survival analysis.

Figure 1

(A) Multigene view of lung adenocarcinoma Heat Maps Comparison of all Genes in the study of Hou lung [50]. The expression of KIAA0101 in lung adenocarcinoma was higher than that in the normal control group. (B) Summary view of KIAA0101. The transcription level of KIAA0101 in different types of cancer. Parameter setting: gene: KIAA0101, threshold (P-value): 0.001, threshold (fold change):2, threshold (gene rank): 10%, data type: DNA and mRNA. Note: The color is standardized by the Z-score to describe the relative value in the row. They cannot be used to compare values between rows. Among them, Red signifies gene overexpression or copy gain in the analyses represented by that cell in the table; blue represents the gene's underexpression or copy loss in those analyses. Datasets comprised samples represented as microarray data measuring either mRNA expression on primary tumors, cell lines, or xenografts. (C) Transcription of KIAA0101 in lung adenocarcinoma (from Oncomine, GEPIA, and Ualcan). mRNA expression levels of KIAA0101 were significantly higher in lung adenocarcinoma than in normal tissue. (C1–C6) Shown are the fold change, associated p-values, and overexpression Gene Rank, based on Oncomine 4.5 analysis. Box plot showing KIAA0101 mRNA levels in, respectively, the Hou Lung, Su Lung, Landi Lung, Beer Lung, Selamat Lung and Okayama Lung datasets [50]. (C7) Expression of KIAA0101 in LUAD based on GEPIA analysis; the p-value was 0.0012. (C8) Shows the expression of KIAA0101 in LUAD based on Ualcan analysis; the p-value was 1.62E-12.

Figure 2

Overall survival curves, progression-free survival curves and disease-free survival curves of KIAA0101 in lung adenocarcinoma. The blue curves represent patients with lung adenocarcinoma with low expression of KIAA0101, and the red curves represent patients with lung adenocarcinoma with high expression of KIAA0101. (A1–A6) Six survival curves representing the six different data sets in Table 1 (from PrognoScan databases), respectively. (B1–B6) The six overall survival curves from the GEPIA, Linkedmics, Ualcan, TISIDB, Oncolnc, and TCGA portal databases, respectively. (C1–C2) Disease free survival curves (DFS) of KIAA0101 from the GEPIA database. (D1–D2) Progression free survival curves (PFS) of KIAA0101 from Kaplan Meier-plotter.

Figure 3

Gene set enrichment analysis of the KIAA0101 via the KEGG pathway. (A) Bar chart for gene set enrichment analysis of the KIAA0101 via the KEGG pathway. (B) KEGG pathway annotations of the cell cycle pathway (hsa04110). Red denotes leading edge genes; green denotes the remaining genes.

Figure 4

KIAA0101 highly correlated genes. (A) Pearson test was used to analyze the correlation between KIAA0101 and differentially expressed genes in LUAD. (B, C) Heat maps showing the genes that correlated positively and negatively with KIAA0101 in LUAD (top 50). Red indicates positively correlated genes, green indicates negatively correlated genes. (D, E) The network view summarizes the predicted association network of proteins that are strongly related to the protein product of KIAA0101. Network nodes are proteins. The edge represents the functional association of the prediction. A red line indicates the existence of fusion evidence, a green line represents neighborhood evidence, a blue line represents co-occurrence evidence, a purple line represents experimental evidence, a yellow line represents text mining evidence, and a light blue line represents database evidence.

Figure 5

KIAA0101 highly correlated miRNAs. (A) Volcano plot of KIAA0101 related miRNAs; (B, C) positively and negatively correlated significant miRNA heat plots of KIAA0101. (D) The miRNA volcano map related to the overall survival of LUAD; (E, F) miRNAs positively and negatively related to the overall survival of LUAD, respectively; (G1–G18) the survival curves of KIAA0101 related miRNAs; green represents low expression of the corresponding miRNA, while red represents high expression of the corresponding miRNA.

Figure 6

KIAA0101 highly correlated lncRNAs. (A1–A8) Scatter plots of eight kinds of lncRNAs that correlated positively with KIAA0101 expression. (B1–B8) Scatter plots of eight kinds of lncRNAs that correlated negatively with KIAA0101 expression. (C1–C8) Survival curves of eight kinds of lncRNAs; patients with low expression of lncRNAs have a higher survival rate. (D1–D8) Survival curves of eight kinds of lncRNAs; patients with high expression of lncRNAs have a higher survival rate.

Figure 7

The relationship between immune infiltration and expression of KIAA0101 in lung adenocarcinoma. (A–F) Heat maps of KIAA0101 expression and lymphocytes, immunoinhibitors, immunostimulators, MHC molecules, chemokines, and receptors in different cancers. (G1–G18) are scatter plots of the negative correlation between KIAA0101 expression and lymphocytes in the treatment of lung adenocarcinoma. (H1–H10) are scatter plots of the positive correlation between KIAA0101 expression and lymphocytes in the treatment of lung adenocarcinoma.