Genomic profiling and quantitative metabolomics analysis searching for molecular signature in colorectal cancer

Colorectal cancer (CRC) is one of the most recurrent malignancies and the most common cause of cancer death worldwide. The identification of specific biomarkers can be of great help in the diagnosis, prognosis and development of new targeted therapies to reduce mortality and increase survival for CRC patients. Next-generation sequencing (NGS) techniques allow us to know the complete genomic structure of the neoplastic tissue and enable us to identify changes in tumour transcriptome. In this study, we performed high-throughput transcriptome sequencing on CRC and normal colon tissues (NCT). Total RNAs were extracted from 138 primary CRCs and paired NCTs. Transcriptome analysis revealed differentially expressed genes (DEGs) specific to the tumour. A total of 2599 DEGs were identified in the CRC: 827 and 1772 were significantly up- and down-regulated, respectively. Our dataset was also analysed to identify differential expression genes according to various clinico-pathological features in our CRC cohort, such as tumour location, lymphocytic infiltrate, stage and grade. We observed nine DEGs between right (proximal) and left (distal) colon, twenty DEGs between right colon and rectum, and only one gene differentially expressed between early and late stage. Many studies have shown that the location of the primary CRC tumour, right or left, has a prognostic/predictive value: the location can dictate its behaviour and influences pathology, progression and prognosis. DEG analysis conducted between tumour stages identified only one gene differentially expressed between early and advanced stages: SOX14. This gene is upregulated in stage I tumours compared to advanced stages. It could be a gene related to the early stages of carcinogenesis and could be useful as an early diagnostic marker. RNA sequencing technology revealed the landscape of variation in the CRC transcriptome. Our data increase our knowledge of the expression differences underlying the neoplasm and reveal useful genes that can be used as diagnostic or prognostic markers and, most importantly, as new therapeutic targets. Liquid biopsy involves the use of biological fluids, especially blood, to investigate certain circulating biomarkers present in each subject at a given time. The assessment of circulating polyamines could be a valuable tool. We have therefore profiled eleven polyamines, including spermine and spermidine with their acetylated forms, using a highly sensitive and innovative method: very high-resolution liquid chromatography and mass spectrometry. These data, together with an evaluation of inflammation indices, could represent suitable biomarkers for the identification of CRC patients. Our results revealed good discrimination in distinguishing CRC patients from healthy subjects. Plasma evaluation of ornithine and acetylspermine, as well as the lymphocyte/platelet ratio, revealed useful information on CRC progression. The combined profiles of circulating polyamines and inflammation indices, together with the application of innovative technology, could act as a valuable tool to discriminate patients from different clinical groups. It is useful to investigate various aspects of a neoplasm in order to fully understand its pathogenesis, to be able to investigate possible drugs, and thus to make a breakthrough in treatment and diagnosis. The idea of investigating various aspects of a neoplasm makes it possible to gain an overview of the tumour, and also to find commonalities in order to build a true virtual map of the tumour.

Colorectal cancer (CRC) is one of the most prevalent malignancies and the most common cause of cancer death worldwide. The identification of specific biomarkers aids diagnosis and the development of new targeted therapies. We performed transcriptome sequencing on 138 CRC and paired normal tissues. Next-generation sequencing (NGS) techniques allow us to know the complete genomic structure of the tumour and identify changes in the tumour transcriptome. NGS revealed tumour-specific differentially expressed genes (DEGs): a total of 2599 DEGs. We also identified DEGs according to location (9 DEGs between right and left colon, 20 DEGs between right colon and rectum), stage (only one DEG between early and late stages: SOX14) and CRC grade. SOX14 is upregulated in stage I tumours compared to late stage tumours. It could be a gene related to the early stages of carcinogenesis and be useful as an early diagnostic marker. Our data increase our knowledge of the expression differences underlying malignancy and reveal useful genes that can be used as diagnostic or prognostic markers and as new therapeutic targets. Liquid biopsy involves the use of biological fluids to study certain circulating biomarkers present in each subject at a given time. The evaluation of circulating polyamines could be a valuable tool. We therefore profiled eleven polyamines in plasma, using a sensitive and innovative method: ultra-high resolution liquid chromatography and mass spectrometry. Our results revealed good discrimination in distinguishing CRC patients from healthy subjects. Circulating polyamine profiles and indices of inflammation could be suitable biomarkers for the identification of patients with CRC. It is useful to investigate the various aspects of a neoplasm to fully understand its pathogenesis and to make progress in treatment and diagnosis. The various aspects of a neoplasm make it possible to obtain an overview of the tumour and build a virtual map of the tumour