NcRNA-regulated CAPZA1 associated with prognostic and immunological effects across lung adenocarcinoma



doi: 10.3389/fonc.2022.1025192.


eCollection 2022.

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Tingting Qin et al.


Front Oncol.


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Abstract

Recent discoveries have suggested that the F-actin capping protein α1 subunit (CAPZA1) in various human tumors could play a significantly important role in regulating cell proliferation, metastasis, and epithelial-mesenchymal transition. However, the immune-regulating role of CAPZA1 in the initiation and development of lung adenocarcinoma (LUAD) remains unclear. In our research, we first found that CAPZA1 serves as an oncogene in pan-cancers from the TCGA data and higher CAPZA1 expression process unfavorably prognostic value in LUAD based on starBase database, PrognoScan, and LOGpc database. Then, in our analyses, lncRNAs AC026356.1 in LUAD acted as a competitive endogenous RNA (ceRNA) of miR-30d-5p, which might be the possible regulatory miRNA of CAPZA1 based on the starBase database. Finally, we confirmed that CAPZA1 expression had a tightly positive correlation with immune infiltration cells, immune infiltration markers, TMB, MSI, immune score, stromal score, and immune checkpoints, indicating that CAPZA1 was a markedly reliable therapeutic target for immunological antitumor strategies. In conclusion, our investigations revealed that CAPZA1 might function as an immune-associated biomarker in the development and treatment of LUAD, thereby acting as a promising prognostic and therapeutic target against LUAD.


Keywords:

CAPZA1; LUAD; ceRNA; immunotherapy; prognosis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures


Figure 1



Figure 1

Expression analysis for CAPZA1 in multiple cancers. (A) The expression of CAPZA1 in 33 types of human cancer based on the TCGA cancer and normal data in TIMER. (B–N) CAPZA1 expression in the starBase BLCA. (B), BRCA (C), CHOL (D), ESCA (E), HNSC (F), KIRC (G), KIRP (H), LIHC (I), LUAD (J), LUSC (K), STAD (L), THCA (M), and UCEC (N) tissues compared with corresponding TCGA normal tissues. *p-value < 0.05; ***p-value < 0.001.


Figure 2



Figure 2

The overall survival (OS) analysis for CAPZA1 in various human cancers determined by starBase. (A–M) The OS plot of CAPZA1 in BLCA. (A), BRCA (B), CHOL (C), ESCA (D), HNSC (E), KIRC (F), KIRP (G), LIHC (H), LUAD (I), LUSC (J), STAD (K), THCA (L), and UCEC (K).


Figure 3



Figure 3

The prognostic value of CAPZA1. (A) Prognostic value of CAPZA1 in multiple data sets. (B–F) The representative survival curves.


Figure 4



Figure 4

Identification of miR-30d-5p as a potential upstream miRNA of CAPZA1 in LUAD. (A) The miRNA- CAPZA1 regulatory network established by Cytoscape software. (B) The expression correlation between predicted miRNAs and CAPZA1 in LUAD as analyzed by the starBase database. (C) The expression correlation between miR-30d-5p and CAPZA1 in LUAD as analyzed by the starBase database. (D) The expression of miR-30d-5p in LUAD and control normal samples determined by the starBase database. (E) The prognostic value of let-7c-5p in LUAD assessed by the starBase database.


Figure 5



Figure 5

Expression analysis and survival analysis for upstream lncRNAs of miR-30d-5p in LUAD (A–D, I–L). The expression of LINC01133 (A), LINC02535 (B), AL024507.2 (C), LINC00707 (D), AL139125.2 (I), AC026356.1 (J), AL049840.4 (K), and GACAT2 (L) in the starBase database. (E–H, M–P) The OS analysis for LINC01133 (E), LINC02535 (F), AL024507.2 (G), LINC00707 (H), AL139125.2 (M), AC026356.1 (N), AL049840.4 (O), and GACAT2 (P) in LUAD.


Figure 6



Figure 6

The model of AC026356.1–miR-30d-5p–CAPZA1 axis in LUAD.


Figure 7



Figure 7

The relationship of immune cell infiltration with CAPZA1 level in LUAD. (A) The correlation of CAPZA1 expression level with B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, or dendritic cell infiltration level in LUAD. (B) The infiltration level of various immune cells under different copy numbers of CAPZA1 in LUAD. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001.


Figure 8



Figure 8

Correlation of CAPZA1 and AC026356.1 expression with PD-1, PD-L1, and CTLA-4 expression in LUAD. (A) Spearman correlation of CAPZA1 with expression of PD-L1 in LUAD using TIMER. (B) Spearman correlation of CAPZA1 with expression of PD-1 in LUAD using TIMER. (C) Spearman correlation of CAPZA1 with expression of CTLA-4 in LUAD using TIMER. (D) The expression correlation of AC026356.1 with PD-L1 in LUAD was determined by the starBase database. (E) The expression correlation of AC026356.1 with PD-1 in LUAD determined by the starBase database. (F) The expression correlation of AC026356.1 with CTLA-4 in LUAD was determined by the starBase database.


Figure 9



Figure 9

Correlation of CAPZA1 expression with the immunophenoscore (IPS) in HCC. (A) ips_ctla4_neg_pd1_neg, (B) ips_ctla4_neg_pd1_pos, (C) ips_ctla4_pos_pd1_neg, and (D) ips_ctla4_pos_pd1_pos.


Figure 10



Figure 10

The correlation of CAPZA1 with immunotherapy and potential mechanisms. (A) Pearson correlation of CAPZA1 with MSI in LUAD. (B) Pearson correlation of CAPZA1 with TMB in LUAD. (C) Pearson correlation of CAPZA1 with ImmuneScore in LUAD. (D) Pearson correlation of CAPZA1 with StromalScore in LUAD. (E) Pearson correlation of CAPZA1 with estimateScores in LUAD. (F) Potential signaling pathway.

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