Abstract
Locally recurrent rectal cancer (LRRC) leads to a poor prognosis and appears as a clinically predominant pattern of failure. In this research, whole-exome sequencing (WES) was performed on 21 samples from 8 patients to search for the molecular mechanisms of LRRC. The data was analyzed by bioinformatics. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the candidate genes. Immunohistochemistry was used to detect the protein expression of LEF1 and CyclinD1 in LRRC, primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) specimens. The results showed that LRRC, PRC, and NRRC had 668, 794, and 190 specific genes, respectively.FGFR1 and MYC have copy number variants (CNVs) in PRC and LRRC, respectively. LRRC specific genes were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and ATP binding. The specific signaling pathways of LRRC were Wnt signaling pathway, gap junction, and glucagon signaling pathway, etc. The transcriptional and translational expression levels of genes including NFATC1, PRICKLE1, SOX17, and WNT6 related to Wnt signaling pathway were higher in rectal cancer (READ) tissues than normal rectal tissues. The PRICKLE1 mutation (c.C875T) and WNT6 mutation (c.G629A) were predicted as “D (deleterious)”. Expression levels of LEF1 and cytokinin D1 proteins: LRRC > PRC > NRRC > normal rectal tissue. Gene variants in the Wnt signaling pathway may be critical for the development of LRRC. The present study may provide a basis for the prediction of LRRC and the development of new therapeutic drugs.
Highlights
Recurrent rectal cancer (LRRC) is defined as the recurrence of rectal cancer (READ) only within the pelvis after radical resection [1]
The results showed that Locally recurrent rectal cancer (LRRC), primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) had 668, 794, and 190 specific genes, respectively
Exome-coding DNA was captured with Agilent SSEL XTHS Human All Exon V6 (Agilent Technologies, Santa Clara, CA, USA), and the libraries were sequenced on an Illumina NovaSeq Platform (Illumina, San Diego, CA, USA), which produced 350-bp paired-end reads
Summary
Recurrent rectal cancer (LRRC) is defined as the recurrence of rectal cancer (READ) only within the pelvis after radical resection [1]. LRRC generally occurs within 2-3 years after the initial surgery [4]. Non-recurrent rectal cancer (NRRC) is defined as READ that has not recurred within 3 years after radical surgery. The local control (LC) rate for clinically localized READ ranges between 92% and 96% [5, 6]. Up to 50% of recurrent READ patients have synchronously diagnosed distant metastases [7, 8]. Nearly half of the patients with recurrence of READ are limited in the pelvis, which is defined as LRRC [8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
