Differential expression of CXCL10 in public databases (data from the GEO database).
A total of 890 differentially expressed (DE) genes were identified in pancreatic tumour tissues and normal tissues in the GSE56560 dataset. Compared with all chemokines and their receptors discovered to date, 10 DE chemokines or their receptors overlapped in the GSE56560 dataset, of which one chemokine was CXCL10 (Fig. 1).
CXCL10 expression in PDAC samples from the TCGA database.
Studies have reported that CXCL10 is highly expressed in many common tumours and may serve as an oncogene in PAAD, including pancreatic adenocarcinoma (PAAD) and bladder urothelial carcinoma, lung adenocarcinoma, breast invasive carcinoma, prostate adenocarcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, liver hepatocellular carcinoma, colon adenocarcinoma, lymphoid neoplasm diffuse large B-cell lymphoma, thymoma, oesophageal carcinoma, rectum adenocarcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, testicular germ cell tumours, thyroid carcinoma, and uterine corpus endometrial carcinoma (P<0.05) (Fig. 2A). Compared with 171 matched paracancerous tissues, CXCL10 was significantly highly expressed in 179 PAAD tissues (data from the TCGA database) (P<0.05) (Fig. 2B).
Patients with PAAD with high CXCL10 expression have a short survival time (data from the TCGA dataset).
In the aggregate, 178 pancreatic cancer patients with CXCL10 expression information from the TCGA dataset were included in the present study. Patients were divided into high- and low-expression groups according to the median value of the expression. Compared with the low CXCL10 group, the high CXCL10 group had a prominently poorer prognosis (P=0.0051; Fig. 3).
The relationship between CXCL10 and tumour-infiltrating immunocytes.
We estimated the relationship between CXCL10 and tumour-infiltrating immune cells (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells). The analysis showed that neutrophils (PAAD: R=0.39, P<0.001) and dendritic cells (PAAD: R=0.442, P<0.001) showed the most significant correlation (Fig. 4).
Expression of CXCL10 in PAAD patients (data from the tissue microarray dataset).
For each individual point, the final H‑SCORE for CXCL10 expression was represented by the average H‑SCORE of duplicates in TMA. The mean H‑SCORE in PAAD tissues was 116.7 (95% CI, 110.5‑122.8). The mean H‑SCORE in matched paracancerous tissues was 71.32 (95% CI, 66.44‑76.20). The discrepancy in the CXCL10 expression level between PAAD tumour tissues and matched paracancerous tissues was significant (P<0.0001; Fig. 5A). Positive staining for CXCL10 in PAAD tissues (Fig. 5B) and negative staining for CXCL10 in matched paracancerous tissues (Fig. 5C).
Correlation between CXCL10 and clinicopathological features (data from tissue microarray dataset).
Statistical results revealed that for patients with PAAD, an increased level of CXCL10 expression was associated with T stage (P=0.020). No significant correlations were observed between CXCL10 expression and sex, tumour site, histological grade, tumour site, age, vascular invasion, N stage, or M stage (P >0.05; Table II).
High expression of CXCL10 predicted a shorter survival time for patients with PAAD (data from the tissue microarray dataset).
Prognostic analysis was also conducted based on the tissue microarray dataset. Kaplan‑Meier survival analysis and the log-rank test suggested that patients with high CXCL10 expression suffered a prominently poorer prognosis than those with low expression (log-rank test: P = 0.012, Fig. 6). This also shows that CXCL10 may be used as an independent target for the treatment of PAAD.
Multivariate Cox regression analysis suggested that CXCL10 was an independent prognostic factor for PAAD patients (data from the tissue microarray dataset).
First, univariate analysis was used to screen for prognostic factors. Clinicopathological evaluation suggested that CXCL10 expression (P=0.015), age (P=0.037), histological grade (P=0.010), N stage (P=0.003) and TNM stage (P=0.003) were prominently related to poor overall survival. Due to associations of N stage, M stage and TNM stage, only the TNM stage variable was included in the Cox regression analysis. The results suggested that histological grade (P=0.001), age (P=0.005), CXCL10 (P=0.024) and TNM stage (P=0.017) were independent prognostic factors for pancreatic cancer patients. CXCL10 [adjusted hazards ratio 1.697 (95% CI 1.073 to 2.684)] in Cox multivariate regression analysis suggested that in PAAD patients, patients with high CXCL10 expression had an approximately 1.7 times higher risk of death than patients with low CXCL10 expression. Therefore, this also indicates that CXCL10 is an independent prognostic factor for PAAD patients (Fig. 7).