[mG-lncRNAs are potential biomarkers for prognosis and tumor microenvironment in patients with colon cancer].

OBJECTIVE

To assess the value of mG-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).

METHODS

We screened mG-lncRNAs from TCGA to construct an mG-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by mG-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.

RESULTS

We identified a total of 1722 mG-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group ( < 0.05). The tumor stemness index was negatively correlated with the risk score (=-0.19; =7.3e-05). Patients in the high-risk group had higher stromal cell scores (=0.0028) and higher total scores (=0.007) with lowered expressions of activated mast cells (=-0.11; =0.045) and resting CD4+ T cells (=-0.14; =0.01) and increased expressions of most immune checkpoints ( < 0.05). ATXN2 (= 0.006) and G3BP1 (=0.007) were identified as the key targets regulated by mG-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.

CONCLUSION

The risk model based on 12 mG-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.