Eva Hofsli

Cancer cachexia is a complex syndrome marked by involuntary weight and muscle loss, often driven by systemic inflammation. This multicenter, longitudinal observational study investigated circulating microRNA (miRNA) profiles in patients with unresectable locally advanced or metastatic colorectal cancer, comparing those with and without cachexia and inflammation. A total of 168 patients were categorized into four groups based on cachexia and C-reactive protein (CRP) levels. Cachexia was defined using the 2011 consensus criteria, incorporating weight loss, low BMI, and sarcopenia. Patients with both cachexia and systemic inflammation exhibited significantly distinct miRNA profiles as well as poorer overall survival (HR 2.10, p < 0.001) compared to patients with neither condition. No significant differences were observed in patients lacking either cachexia or inflammation or both. Inflammatory cachexia emerged as a biologically distinct entity, with 82 differentially expressed miRNAs. The miR-320-family, miR-6087, miR-4488, miR-29a-3p, miR-194-5p, and miR-10a-5p were most altered, several of which are linked to muscle mass, metabolism, lipid, and protein synthesis. These findings highlight the pivotal role of systemic inflammation in cancer cachexia and support its inclusion in diagnostic criteria. Moreover, circulating miRNAs may serve as promising biomarkers for identifying cachexia in cancer patients.

Identification of metastasis-associated microRNAs in serum from rectal cancer patients Identification of metastasis-associated microRNAs in serum from rectal cancer patients

Background: microRNAs (miRNAs) exist in blood in an apparently stable form. We have explored whether serum miRNAs can be used as non-invasive early biomarkers of colon cancer. Methods: Serum samples from 30 patients with colon cancer stage IV and 10 healthy controls were examined for the expression of 375 cancer-relevant miRNAs. Based on the miRNA profile in this study, 34 selected miRNAs were measured in serum from 40 patients with stage I-II colon cancer and from 10 additional controls. Results: Twenty miRNAs were differentially expressed in serum from stage IV patients compared with controls (P<0.01). Unsupervised clustering revealed four subgroups; one corresponding mostly to the control group and the three others to the patient groups. Of the 34 miRNAs measured in the follow-up study of stage I-II patients, 21 showed concordant expression between stage IV and stage I-II patient. Based on the profiles of these 21 miRNAs, a supervised linear regression analysis (Partial Least Squares Regression) was performed. Using this model we correctly assigned stage I-II colon cancer patients based on miRNA profiles of stage IV patients. Conclusion: Serum miRNA expression profiling may be utilised in early detection of colon cancer.

Neuroendocrine tumours (NETs) comprise a heterogenous group of malignancies with an often unpredictable course, and with limited treatment options. Thus, new diagnostic, prognostic, and therapeutic markers are needed. To shed new lights into the biology of NETs, we have by cDNA transcript profiling, sought to identify genes that are either up- or downregulated in NE as compared with non-NE tumour cells. A panel of six NET and four non-NET cell lines were examined, and out of 12 743 genes examined, we studied in detail the 200 most significantly differentially expressed genes in the comparison. In addition to potential new diagnostic markers (NEFM, CLDN4, PEROX2), the results point to genes that may be involved in the tumorigenesis (BEX1, TMEPAI, FOSL1, RAB32), and in the processes of invasion, progression and metastasis (MME, STAT3, DCBLD2) of NETs. Verification by real time qRT–PCR showed a high degree of consistency to the microarray results. Furthermore, the protein expression of some of the genes were examined. The results of our study has opened a window to new areas of research, by uncovering new candidate genes and proteins to be further investigated in the search for new prognostic, predictive, and therapeutic markers in NETs.