Recent, large-scale expression–based subtyping has advanced our understanding of the genomic landscape of colorectal cancer (CRC) and resulted in a consensus molecular classification that enables the categorization of most CRC tumors into one of four consensus molecular subtypes (CMS). Currently, major progress in characterization of immune landscape of tumor-associated microenvironment has been made especially with respect to microsatellite status of CRCs. While these studies profoundly improved the understanding of molecular and immunological profile of CRCs heterogeneity less is known about repertoire of the tumor infiltrating immune cells of each CMS.In order to comprehensively characterize the immune landscape of CRC we re-analyzed a total of 15 CRC genome-wide expression data sets encompassing 1597 tumors and 125 normal adjacent colon tissues. After quality filtering, CRC clusters were discovered using a combination of multiple clustering algorithms and multiple validity metrics. CIBERSORT algorithm was used to compute relative proportions of 22 human leukocyte subpopulations across CRC clusters and normal colon tissue. Subsequently, differential expression specific to tumor epithelial cells was calculated to characterize mechanisms of tumor escape from immune surveillance occurring in particular CRC clusters.Our results not only characterize the common and cluster-specific influx of immune cells into CRCs but also identify several deregulated gene targets that may contribute to improvement of immunotherapeutic strategies in CRC.

There is evidence that insertion of viral DNA into a mammalian genome can lead to alterations of methylation patterns. The aim of the present study was to examine the presence of DNA sequences of five human DNA viruses (assessed by PCR): JC polyoma virus (JCV), human adenovirus (AdV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) and human papillomavirus (HPV) in a cohort of 186 sporadic colorectal cancers (CRCs) and related these data with the methylation status of six CpG island methylator phenotype (CIMP)-specific genes (MLH1, CACNA1G, NEUROG1, IGF2, SOCS1, RUNX3) and seven cancer-related genes markers (p16, MINT1, MINT2, MINT31, EN1, SCTR and INHBB) assessed by methylation-specific PCR in 186 and 134 CRC cases, respectively. The AdV, KSHV and HPV were detected in four (2%), two (1%) and zero CRC cases, respectively, and thus were excluded from further analyses. Although 19% and 9% of the CRCs were positive for EBV and JCV, respectively, no associations between virus presence and CpG island methylation were found after correction for multiple testing. Our results demonstrate that the presence of DNA sequences of JCV and EBV in CRC is unrelated to the methylation of the 13 cancer-related CpG islands and CIMP.

Abstract:Background: Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors.Aim: we focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911CMaterial and methods: The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used.Results: We found that: i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391,3.7782) p=0.038], ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215,0,9131) p=0.031] for an individual with at least one A allele at this locus. Conclusions:1. the XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer.2. the NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.

Over the last decades, transcriptome profiling emerged as one of the most powerful approaches in oncology, providing prognostic and predictive utility for cancer management. The development of novel technologies, such as revolutionary next-generation sequencing, enables the identification of cancer biomarkers, gene signatures, and their aberrant expression affecting oncogenesis, as well as the discovery of molecular targets for anticancer therapies. Transcriptomics contribute to a change in the holistic understanding of cancer, from histopathological and organic to molecular classifications, opening a more personalized perspective for tumor diagnostics and therapy. The further advancement on transcriptome profiling may allow standardization and cost reduction of its analysis, which will be the next step for transcriptomics to become a canon of contemporary cancer medicine.