A new clinical prognostic nomogram for liver cancer based on immune score

PLoS One. 2020 Jul 30;15(7):e0236622. doi: 10.1371/journal.pone.0236622. eCollection 2020.

Abstract

Background: Increased attention is being paid to the relationship between the immune status of the tumor microenvironment and tumor prognosis. The application of immune scoring in evaluating the clinical prognosis of liver cancer patients has not yet been explored. This study sought to clarify the association between immune score and prognosis and construct a clinical nomogram to predict the survival of patients with liver cancer.

Methods: A total of 346 patients were included in our analysis datasets downloaded from The Cancer Genome Atlas (TCGA) dataset. A Cox proportional-hazards regression model was used to estimate the adjusted hazard ratios (HRs). A nomogram was built based on the results of multivariate analysis and was subjected to bootstrap internal validation. The predictive accuracy and discriminative ability were measured by the concordance index (C-index) and the calibration curve. Through the functional analysis of differential expression of genes with different immune scores, the target genes were screened out.

Results: In comparison with patients with low immune scores, those with intermediate and high immune scores had significantly improved survival time [HR and 95% confidence interval (CI): 0.54 (0.30-0.97) and 0.51 (0.27-0.97), respectively]. The C-index for survival time prediction was 0.66 (95% CI: 0.60-0.71). The calibration plot for the probability of survival at three or five years showed good agreement between prediction by the nomogram and actual observations. The top 10 hub genes were CXCL8(chemokine (C-X-C motif) ligand 8), SYK(spleen tyrosine kinase), CXCL12(chemokine (C-X-C motif) ligand 12), CXCL10 (chemokine (C-X-C motif) ligand10), CXCL1(chemokine (C-X-C motif) ligand1), CCL5(chemokine (C-C motif) ligand 5), CCL20(chemokine (C-C motif) ligand 20), LCK, CXCL11(chemokine (C-X-C motif) ligand 11), CCR5(chemokine (C-C motif) receptor 5). More importantly, we found that the high expression of CXCL8 and CXCL1 were related to the prognosis.

Conclusions: High and/or intermediate immune scores are significantly correlated with better survival time in patients with liver cancer. Moreover, nomograms for predicting prognosis may help to estimate the survival of patients. We also propose that CXCL8 and CXCL1 may be a potential therapeutic target for liver cancer treatment.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Databases, Factual
  • Female
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Kaplan-Meier Estimate
  • Liver Neoplasms / immunology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nomograms*
  • Proportional Hazards Models
  • Syk Kinase / genetics
  • Syk Kinase / metabolism
  • Young Adult

Substances

  • Chemokine CXCL12
  • Interleukin-8
  • Syk Kinase

Grants and funding

The author(s) received no specific funding for this work.