4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients

Background

Cholangiocarcinoma (CCA), which includes extrahepatic cholangiocarcinoma (exCCA) and intrahepatic cholangiocarcinoma (iCCA), is a primary malignancy which is often diagnosed as advanced stage and inoperable. The poor sensitivity of clinical diagnosis and lack of effective biomarkers to guide treatment are the main problems to be tackled. Identification of new and effective biomarkers is necessary to assist early diagnosis and prognosis of CCA.

Methods

Deep sequencing targeting 450 cancer genes was performed on FFPE and matching blood samples were collected from 63 CCA patients. Genomic alterations (GAs) including single nucleotide variations, short and long insertions and deletions, copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The correlation analysis was performed by One-way ANOVA.

Results

A total of 63 (35 male and 28 female) Chinese CCA patients, including 40 intrahepatic CCA (iCCA) and 23 extrahepatic CCA (exCCA), were analyzed in this study. The most commonly altered genes included TP53 (41.27%, 26/63), KRAS (31.75%, 20/63), ARIK1A and IDH1 (15.87%, 10/63, for both), SMAD4 (14.29%, 9/63), FGFR2 and BAP1 (12.70%, 8/63, for both) and CDKN2A (11.11%, 7/63). The mutation of LRP2 specifically occurred with low frequency (7.5%, 3/40) in iCCA patients. There were 24 patients aged 50 to 70 years, 6 patients aged more than 70 years and 10 patients aged less than 50 years (younger group). Notably, the mutations of LRP2 were detected only in the younger group, and statistical analysis showed the significant correlation between LRP2 and younger iCCA patients (P = 0.02). Also, 2 of the 3 patients with LRP2 mutations harbored high TMB (TMB-H, more than 10 Muts/Mb). Statistical analysis showed a significant association of LRP2 and TMB-H.

Conclusions

The mutation of LRP2 is associated with younger Chinese iCCA patients. The correlation of LRP2 and TMB-H represents a better mutational burden and probably a better prognosis of younger iCCA patients with LRP2 mutations. Our results support that LRP2 may be a potential biomarker for the diagnosis and prognosis of younger Chinese iCCA patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.