Scientific Lit picture 05

Scientific Literature Review: Cancer

Circulating or tissue micro-RNAs and extracellular vesicles as potential lung cancer biomarkers: a systematic review
Song Y, Yu X, Zang Z, Zhao G. Int J Biol Markers 2017; doi: 10.5301/ijbm.5000307 [Epub ahead of print]

For both lung cancer patients and clinical physicians, tumor biomarkers for more efficient early diagnosis and prediction of prognosis are always wanted. Biomarkers in circulating serum, including microRNAs (miRNAs) and extracellular vesicles, hold the greatest possibilities to partially substitute for tissue biopsy. In this systematic review, studies on circulating or tissue miRNAs and extracellular vesicles as potential biomarkers for lung cancer patients were reviewed and are discussed. Furthermore, the target genes of the miRNAs indicated were identified through the miRTarBase, while the relevant biological processes and pathways of miRNAs in lung cancer were analysed through MiRNA Enrichment Analysis and Annotation (MiEAA). In conclusion, circulating or tissue miRNAs and extracellular vesicles provide us with a window to explore strategies for diagnosing and assessing prognosis and treatment in lung cancer patients.

Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study
Hynes SO, Coleman HG, Kelly PJ et al. Histopathology 2017; 71(1): 12–26

AIMS: Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of the tumour microenvironment has not been adopted into routine practice. The study aim was to identify those tumour microenvironmental features that are most likely to provide prognostic information and be feasible to use in routine pathology reporting practice.

METHODS AND RESULTS: On the basis of existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative hematoxylin and eosin (H&E)-stained whole tumour sections from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn’s disease-like reaction were associated with significantly reduced risks of CRC-specific death [adjusted hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.31–0.76, and HR 0.60, 95% CI 0.42–0.84, respectively]. The presence of >50% tumour stromal percentage, as assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95% CI 1.06–2.41). A composite ‘fibroinflammatory score’ (0–3), combining dichotomized scores of these three features, showed a highly significant association with survival outcomes. Those with a score of ≥2 had an almost 2.5-fold increased risk of CRC-specific death (HR 2.44, 95% CI 1.56–3.81) as compared with those scoring zero. These associations were stronger in microsatellite instability (MSI)-high tumours, potentially identifying a subset of MSI-high colon cancers that lack characteristic morphological features and have an associated worse prognosis.

CONCLUSIONS: In summary, reporting on H&E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer, and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.

METHODS: Serum samples were collected from 60 patients with primary colorectal cancer, 40 patients with colorectal polyps and 50 healthy controls. Serum miR-135a-5p expression levels were detected by reverse transcription quantitative real-time quantitative polymerase chain reaction. Serum carcinoembryonic antigen and carbohydrate antigen 199 concentrations were detected by MODULAR ANALYTICS E170.

RESULTS: The relative expression level of serum miR-135a-5p in colorectal cancer patients, colorectal polyps patients and healthy controls was 2.451 (1.107, 4.413), 0.946 (0.401, 1.942) and 0.949 (0.194, 1.415), respectively, indicating that it was significantly higher in colorectal cancer patients than that in the other two groups (U = 351.0, 313.0, both P <0.001). Additionally, it was significantly correlated with different degrees of tumour differentiation (U = 215.0, P = 0.029) and different tumour stages (U = 202.0, P = 0.013). There was no significant correlation between the relative expression of serum miR-135a-5p and carcinoembryonic antigen (r2 = 0.023, P = 0.293) or carbohydrate antigen 199 (r2 = 0.067, P = 0.068) in colorectal cancer patients. Compared with colorectal polyps group, AUCROC of serum miR-135a-5p in colorectal cancer group was 0.832 with 95% CI 0.73-0.93; compared with healthy control group, AUCROC was 0.875 with 95% CI 0.80-0.95.

CONCLUSION: Serum miR-135a-5p expression in colorectal cancer patients was higher than that in patients with colorectal polyps and healthy controls, suggesting that serum miR-135a-5p may prove to be an important biomarker for auxiliary diagnosis of colorectal cancer.

AFM and QCM-D as tools for the distinction of melanoma cells with a different metastatic potential
Sobiepanek A, Milner-Krawczyk M, Lekka M, Kobiela T. Biosens Bioelectron 2017; 93: 274–281

Malignant melanoma is one of the most dangerous skin cancer originating from melanocytes. Thus, an early and proper melanoma diagnosis influences significantly the therapy efficiency. The melanoma recognition is still difficult, and generally, relies on subjective assessments. In particular, there is a lack of quantitative methods used in melanoma diagnosis and in the monitoring of tumour progression. One such method can be the atomic force microscopy (AFM) working in the force spectroscopy mode combined with quartz crystal microbalance (QCM), both applied to quantify the molecular interactions. In our study we have compared the recognition of mannose type glycans in melanocytes (HEMa-LP) and melanoma cells originating from the radial growth phase (WM35) and from lung metastasis (A375-P). The glycosylation level on their surfaces was probed using lectin concanavalin A (Con A) from Canavalia ensiformis. The interactions of Con A with surface glycans were quantified with both AFM and QCM techniques that revealed the presence of various glycan structural groups in a cell-dependent manner. The Con A – mannose (or glucose) type glycans present on WM35 cell surface are rather short and less ramified while in A375-P cells, Con A binds to long, branched mannose and glucose types of oligosaccharides.