Investigating the role of IDO1 in tumors: correlating IDO1 expression with clinical pathological features and prognosis in lung adenocarcinoma patients

Abstract

Purpose: This study aimed to investigate the role and expression patterns of IDO1 in various tumors, focusing on its correlation with clinical pathological characteristics and prognosis in patients specifically diagnosed with lung adenocarcinoma.

Methods: Pan-cancer analysis assessed IDO1 function across different tumor types. Bioinformatics tools, immunohistochemistry techniques, and statistical analyses were employed to evaluate IDO1 expression levels and their association with clinical pathological features and prognosis in patients with lung adenocarcinoma.

Results: IDO1 was found to be significantly overexpressed in various types of tumors, with higher levels correlating with poorer progression-free survival (PFS) and overall survival (OS). In lung adenocarcinoma patients, IDO1 protein was predominantly localized to the cytoplasm and cell membrane of tumor cells, with higher expression observed in tumor cells closer to normal lung tissue. Statistical analysis revealed no significant differences in IDO1 expression based on the patient's clinical data, including gender, age, tumor location, allergy history, hypertension history, cardiovascular disease history, tumor history, diabetes (both type 1 and type 2), body mass index, smoking history, family history, alcohol history, and tumor maximum diameter (P > 0.05). However, IDO1 expression positively correlated with lymph node metastasis, pleural invasion, tumor recurrence, lower tumor differentiation, solid tumor components, preoperative chemotherapy, and clinical tumor, node, metastasis (TNM) staging (*P < 0.05), while negatively correlating with prior surgical history (*P < 0.05). Patients exhibiting high IDO1 expression levels demonstrated significantly worse PFS and OS (***P < 0.001 and **P = 0.003, respectively).

Conclusion: High IDO1 expression in lung adenocarcinoma correlates with increased tumor invasiveness, metastatic potential, advanced clinical stage, and poorer prognosis.

Keywords: Bioinformatics; Expression; Function; IDO1; Lung adenocarcinoma; Prognosis.

Figure 1. Pan-cancer IDO1 expression and role.

(A) IDO1 expression in various cancers and paired normal tissues from the SangerBox database (*P < 0.05, **P < 0.01, ***P < 0.001). (B) Network diagram illustrating the relationship between IDO1 and other human proteins from the STRING database. (C) Correlation scores between IDO1 and other human proteins from the STRING database. (D) IDO1 expression in various cancers and paired normal tissues from the GEPIA database. (GBM, Glioblastoma multiforme; GBMLGG, Glioma; LGG, Brain Lower Grade Glioma; UCEC, Uterine Corpus Endometrial Carcinoma; BRCA, Breast invasive carcinoma; CESC, Cervical squamous cell carcinoma and endocervical adenocarcinoma; ESCA, Esophageal carcinoma; STES, Stomach and Esophageal carcinoma; KIRP, Kidney renal papillary cell carcinoma; KIPAN, Pan-kidney cohort; COAD, Colon adenocarcinoma; COADREAD, Colon adenocarcinoma/Rectum adenocarcinoma Esophageal carcinoma; PRAD, Prostate adenocarcinoma; STAD, Stomach adenocarcinoma; HNSC, Head and Neck squamous cell carcinoma; KIRC, Kidney renal clear cell carcinoma; LIHC, Liver hepatocellular carcinoma; SKCM, Skin Cutaneous Melanoma; BLCA, Bladder Urothelial Carcinoma; OV, Ovarian serous cystadenocarcinoma; PAAD, Pancreatic adenocarcinoma; TGCT, Testicular Germ Cell Tumors; UCS, Uterine Carcinosarcoma; PCPG, Pheochromocytoma and Paraganglioma; ACC, Adrenocortical carcinoma; KICH, Kidney Chromophobe; DLBC, Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; READ, Rectum adenocarcinoma; THYM, Thymoma).

Figure 2. Kaplan–Meier survival curve of human cancers with high and low IDO1 expression analyzed by the SangerBox database (A–H), the GEPAI database (I, J), and the Kaplan–Meier plotter database (K, L).

(A–H) High IDO1 expression was associated with worse DSS and OS in cohorts of GBMLGG, KIRP, LGG, and UVM. (I, J) High IDO1 expression was associated with worse DFS and OS in cohorts of KICH. (K, L) High IDO1 expression was associated with worse EFS and OS in cohorts of myeloma. (DSS, disease-specific survival; DFS, disease-free survival; EFS, event-free survival; OS, overall survival; GBMLGG, Glioma; KIRP, Kidney renal papillary cell carcinoma; LGG, Brain Lower Grade Glioma; KICH, Kidney Chromophobe; UVM, Uveal Melanoma).

Figure 3. The expression and function of IDO1 in lung adenocarcinoma, as well as its relationship with prognosis.

(A) IDO1 expression in lung adenocarcinoma and paired normal tissue from the GEPIA database. (B) High IDO1 expression in lung adenocarcinoma was associated with worse first progression survival in the Kaplan–Meier plotter database. (C, D) High IDO1 expression in lung adenocarcinoma was associated with worse OS in the GSE31210 and GSE50081 datasets. (E) Correlations between IDO1 expression in lung adenocarcinoma and immune cells in the TIMER 2.0 database. (F) Correlations between IDO1 expression in lung adenocarcinoma and gene mutations in the SangerBox database. (G) Correlations between IDO1 expression in lung adenocarcinoma and immune checkpoints in the SangerBox database (LUAD, Lung adenocarcinoma).

Figure 4. Representative images of hematoxylin and eosin (HE) staining and IDO1 immunohistochemical positive staining of different subtypes of lung adenocarcinoma (100x magnification).

(A) HE staining and IDO1 immunohistochemical positive staining in acinar, papillary, and solid subtypes of lung adenocarcinoma. (B) HE staining and IDO1 immunohistochemical positive staining in micropapillary, cribriform, and solid subtypes of lung adenocarcinoma.

Figure 5. The expression of IDO1 in lung adenocarcinoma and its correlation with clinicopathological features and patient prognosis.

(A, B) Tumor cells closer to normal lung tissue exhibit higher expression of IDO1 in lung adenocarcinoma (40x magnification). (C–G) Higher IDO1 scores were observed in patients with lymph node metastasis, recurrence, poorly differentiated tumor cells, preoperative chemotherapy, or higher clinical TNM staging (*P < 0.05, **P < 0.01, ***P < 0.001). (H) High IDO1 expression was associated with worse progression-free survival (PFS) in patients with lung adenocarcinoma (***P < 0.001). (I) High IDO1 expression was associated with worse overall survival (OS) in patients with lung adenocarcinoma (**P = 0.003).