Background: Extramural vascular invasion(EMVI) is a known independent predictor of poor prognosis in rectal cancer, as evidenced by a higher risk of developing metastases and a shorter DFS compared with negative tumours. However, the molecular mechanisms of EMVI genesis remains unclear. The objective of this study is to clarify the distinct molecular characterization of EMVI-positive tumours from that of EMVI-negative tumours.
Methods: DNA was extracted from FFPE tumor specimens and matched normal tissue samples from rectal cancer patients who underwent surgical resection. Comprehensive genomic profiling analysis was performed using a 2.41M size panel covering exon regions of 1,622 genes based on next generation sequencing assay. Somatic Mutations were analyzed to determine the difference of molecular features between EMVI-positive and EMVI-negative patients.
Results: In this retrospective study, a total of 48 rectal cancer patients without distant metastases were included: 17 patients in the EMVI-positive group and 31 patients in the EMVI-negative group. All the EMVI-postive patients had lymph node metastasis and 15 patients had lymph node metastasis in EMVI-negative group. Among all the tumours, the most frequently mutated genes were TP53,APC, KRAS, SMAD4, CHEK2, TCF7L2 and FBXW7. Mutations of TCF7L2 and CHEK2 were more frequently observed in EMVI-positive tumours than that in EMVI-negative tumours with p < 0.05. Survival analysis (Kaplan-Meier) indicated that patients with KRAS mutations(n = 9) had a shorter DFS than patients without KRAS mutations(n = 23) in patients with lymph node metastasis (p < 0.05). In addition, age was significantly associated with DFS according to the survival analysis (p < 0.05).
Conclusions: Several possible candidate genes that may be helpful to characterize the distinct mutational profile of EMVI-positive tumours from EMVI-negative tumours were identified, which may be of great significance in disclosing the molecular mechanism underlying in EMVI initiation and progression. Expanded prospective cohorts are warranted to further elucidate these findings.