Progress in the identification of plasma biomarkers of colorectal cancer

Proteomic analysis of human tissue and plasma samples has been a useful tool in recent years for the identification of potential biomarkers to aid in the early diagnosis of colorectal cancer. However, biomarkers relating to the crucial transition between adenomatous lesions and invasive colorectal malignancy have not previously been described. The work of Choi et al. (Proteomics 2013, 13, 2361–2374) attempts to address this issue. Using plasma samples from age‐matched patients with colorectal adenomas or invasive disease this group identified a range of plasma proteins and cytokines that were differentially expressed. This information not only provides insights into the biology of the adenoma to carcinoma progression sequence but it also represents a step towards the goal of achieving diagnostically accurate and clinically acceptable biomarkers in early colorectal cancer.     

生物信息学分析筛选结直肠癌靶基因及评估预后价值

为寻找与结直肠癌发展和预后相关的潜在关键基因及信号通路.从美国国立信息中心NCBI的GEO数据库获得结直肠癌基因表达数据集GSE106582,通过PCA对样本进行分组,利用GEO2R进行综合分析,筛选结直肠癌与癌旁对照组的差异表达基因;通过DAVID在线工具对差异表达基因进行GO本体分析和KEGG通路富集分析,初步分析...     

Lectin adhesion proteins (P-, L- and E-selectins) as biomarkers in colorectal cancer

Context: Selectins probably participate in the interactions between platelets and other inflammatory cells in cancer invasion and metastasis formation. We assessed a potential relationship of P-, L- and E-selectin in colorectal cancer (CRC) patients in relation to tumour advancement according to TNM classification, and tumour location.

Materials and methods: The study group was composed of 53 CRC patients and 25 healthy subjects. Plasma levels of soluble P-, L- and E-selectins were measured using the immunoenzymatic method with Quantikine kits (R&D Systems, Minneapolis, MN).

Results: The mean levels of all selectins were significantly higher in CRC patients compared to healthy controls. The highest level of sP-selectin was observed in patients with metastases to the liver (stage IV), and was significantly higher than in patients without metastases (stage I/II) and with lymph node metastases (stage III), p?=?.02. The highest levels of sL- and sE-selectin were observed in patients with lymph node metastasis. We also found sP-selectin to be the best predictor of CRC.

Conclusion: Our finding show possible involvement of tested selectins in CRC advancement and forming metastasis. Among sL- and E- selectins, P-selectin plays an important role in the progression of CRC and could be an attractive biomarker with clinical significance.     

ADAM and ADAMTS family proteins and their role in the colorectal cancer etiopathogenesis

The ADAM and ADAMTS families, also called adamalysins belong to an important group of extracellular matrix proteins. The ADAMs family belong to both the transmembrane and secreted proteins, while ADAMTS family only contains secreted forms. Adamalysins play an important role in the cell phenotype regulation via their activities in signaling pathways, cell adhesion and migration. The human proteome contains 21 ADAM, and 19 ADAMTS proteins, which are involved in extracellular matrix remodeling, shedding of various substrates such as: adhesion ligands, growth factors, their receptors and diverse cytokines. Recent studies provide evidence that adamalysins play a crucial role in colorectal cancer (CRC) etiopathogenesis. It seems possible that adamalysins might be used as CRC prediction markers or potential pharmaceutical targets. [BMB Reports 2013; 46(3): 139-150]     

Epigenetic biomarkers in colorectal cancer: premises and prospects

Context: Colorectal cancer is one of the most common cancers worldwide. Epigenetic alterations play an important role in the pathogenesis of the colorectal cancer.

Objective: This review has focused on the most recent investigations, which has suggested potential epigenetic biomarkers in colorectal cancer.

Methods: Evidences were achieved by searching online medical databases including Google scholar, Pubmed, Scopus and Science Direct.

Results: Extensive studies have indicated that aberrant epigenetic modifications could serve as potential biomarkers for diagnosis, prognosis and prediction of colorectal cancer.

Conclusion: Advances in aberrant epigenetic modifications can open new avenues for exploration of reliable and robust biomarkers to improve the management of CRC patients.     

Predictive and prognostic biomarkers in colorectal cancer

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States.Three quarters of patients diagnosed with colorectal cancer will have early s...     

VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death.     

Survival pattern of colorectal cancer in Sub-Saharan Africa: A systematic review and meta-analysis

Cancer incidence is relatively low in sub-Saharan Africa (SSA), however, prognosis is expected to be poor in comparison with high-income countries. Comprehensive evidence is limited on the survival pattern of colorectal cancer patients in the region. We conducted a systematic review and meta-analysis to investigate the pattern of colorectal cancer survival in the region and to identify variation across countries and over time. We searched international databases MEDLINE, Scopus, Embase, Web of Science, ProQuest, CINAHL, and Google Scholar to retrieve studies that estimated survival from colorectal cancer in SSA countries from inception to December 31, 2021 without language restriction. Due to between-study heterogeneity, we performed a random-effects meta-analysis to pool survival rates. To identify study-level sources of variation, we performed subgroup analysis and meta-regression. Results are reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guideline and the protocol was registered in PROSPERO database (CRD42021246935). 23 studies involving 10,031 patients were included in the review, of which, 20 were included in the meta-analysis. The meta-analysis results showed that the pooled 1-, 2-, 3-, 4-, and 5-year survival rates in SSA were 0.74 (95% CI, 0.66–0.81), 0.50 (95% CI, 0.41–0.58), 0.36 (95% CI, 0.27–0.47), 0.31 (95% CI, 0.22–0.42), and 0.28 (95% CI, 0.19–0.38) respectively. Subgroup analyses indicated that the survival rate varied according to year of study, in which those conducted in recent decades showed relatively better survival. The 5-year survival was higher in middle-income SSA countries (0.31; 95%CI: 0.17–0.49) than low-income countries (0.20; 95%CI: 0.11–0.35), however, the difference was not statistically significant. In conclusion, survival from colorectal cancer is low in sub-Saharan Africa compared to other regions. Thus, intervention strategies to improve screening, early diagnosis and treatment of colorectal cancer should be developed and implemented to improve survival in the region.     

Tumor-associated autoantibodies as diagnostic and prognostic biomarkers

In the process of tumorigenesis, normal cells are remodeled to cancer cells and protein expression patterns are changed to those of tumor cells. A newly formed tumor microenvironment elicits the immune system and, as a result, a humoral immune response takes place. Although the tumor antigens are undetectable in sera at the early stage of tumorigenesis, the nature of an antibody amplification response to antigens makes tumor-associated autoantibodies as promising early biomarkers in cancer diagnosis. Moreover, the recent development of proteomic techniques that make neo-epitopes of tumor-associated autoantigens discovered concomitantly has opened a new area of ‘immuno-proteomics’, which presents tumor-associated autoantibody signatures and confers information to redefine the process of tumorigenesis. In this article, the strategies recently used to identify and validate serum autoantibodies are outlined and tumor-associated antigens suggested until now as diagnostic/prognostic biomarkers in various tumor types are reviewed. Also, the meaning of autoantibody signatures and their clinical utility in personalized medicine are discussed. [BMB Reports 2012; 45(12): 677-685]     

Long non-coding RNA-422 acts as a tumor suppressor in colorectal cancer

Colorectal cancer (CRC) is one of the most frequent cancer in numerous of countries worldwidely. The initiation and progression of CRC is an extremely complex process, and have been suggested a correlation with Long non-coding RNAs (lncRNAs). Our results showed that lncRNA-422(ENST00000415820) significantly downregulated in the tissues and serum of CRC patients, and is closely associated with the poor prognosis. Then gain or loss of lncRNA-422 models in SW480 and SW620cells were established. The results showed that lncRNA-422 overexpression inhibited cell proliferation, migration, and invasion. Knockdown of lncRNA-422 promoted tumorigensis. Western blot and qRT-PCR were performed to examine the activity of the PI3K/AKT/mTOR pathway in CRC cells after alternation of lncRNA-422. Results showed that lncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR pathway in CRC.     

Piceatannol promotes apoptosis via up-regulation of microRNA-129 expression in colorectal cancer cell lines

Piceatannol, a naturally occurring analog of resveratrol, has been confirmed as an antitumor agent by inhibiting proliferation, migration, and metastasis in diverse cancer. However, the effect and mechanisms of piceatannol on colorectal cancer (CRC) have not been well understood. This study aimed to test whether piceatannol could inhibit growth of CRC cells and reveal its underlying molecular mechanism.     

Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer

Purpose: Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity is associated with increased susceptibility to infections. In patients with colorectal cancer (CRC), postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1) the relation between the MBL pathway and postoperative infectious complications and survival of patients resected for CRC, and (2) the role of MBL in acute phase response compared to C-reactive protein (CRP). Methods: Preoperative MBL concentration, MBL-associated serine protease (MBL/MASP) activity and CRP were determined in serum from 611 patients and 150 healthy controls. The patients were observed for 8 years. Postoperative infections, recurrence and survival were recorded. Results: The MBL pathway components were increased in the patients compared with the healthy controls (p<0.0001). Low MBL levels were predictive of pneumonia (p=0.01), and pneumonia (n=87) was associated with poor survival (p=0.003; HR=1.5; 95% CI, 1.1 to 1.9). MBL and MBL/MASP activity showed no correlation with CRP (Spearmans =0.02; 95% CI, –0.06 to 0.10). Conclusion: Low preoperative MBL levels are predictive of pneumonia, which is associated with poorer survival. MBL concentration and MBL/MASP activity was not predictive of other postoperative infections or long-term prognosis, and showed no correlation with CRP.     

miR-33a-5p in small extracellular vesicles as non-invasive biomarker for oxaliplatin sensitivity in human colorectal cancer cells

microRNAs (miRNAs) contained in small extracellular vesicles (sEVs) are candidates for non-invasive biomarkers. Oxaliplatin (L-OHP) has been approved for advanced colorectal cancer (CRC) chemotherapy. However, the response to L-OHP differs among CRC patients. In addition, CRC cells often acquire the resistance to L-OHP. This study aimed at the prediction of L-OHP sensitivity by measuring extracellular miRNAs levels. Firstly, we compared intracellular miRNAs expressions in L-OHP-sensitive CRC cells (SW620 and HCT116 cells) with those in acquired and intrinsic L-OHP-resistant cells. In microarray and real-time RT-PCR analyses, the intracellular miR-33a-5p, miR-210–3p, and miR-224–5p expressions were lower in acquired and intrinsic L-OHP-resistant CRC cells than sensitive cells. Furthermore, in SW620 cells, L-OHP sensitivity was decreased by miR-33a-5p inhibitor. On the other hand, miR-210–3p or miR-224–5p inhibitor did not affect L-OHP sensitivity in SW620 cells. Secondly, the amount of miR-33a-5p, miR-210–3p, and miR-224–5p in sEVs was compared. The amount of miR-33a-5p and miR-210–3p in sEVs secreted from acquired and intrinsic L-OHP-resistant cells tended to be small. miR-224–5p was not detected in sEVs secreted from three types of CRC cells examined. To the best of our knowledge, this is the first study demonstrating that miR-33a-5p and/or miR-210–3p in sEVs would be candidates for biomarkers of L-OHP sensitivity. In particular, miR-33a-5p is a promising candidate because it would be directly involved in L-OHP sensitivity.     

Glycans as cancer biomarkers

Background

Non-invasive biomarkers, such as those from serum, are ideal for disease prognosis, staging and monitoring. In the past decade, our understanding of the importance of glycosylation changes with disease has evolved.

Scope of review

We describe potential biomarkers derived from serum glycoproteins for liver, pancreatic, prostate, ovarian, breast, lung and stomach cancers. Methods for glycan analysis have progressed and newly developed high-throughput platform technologies have enabled the analysis of large cohorts of samples in an efficient manner. We also describe this evolution and trends to follow in the future.

Major conclusions

Many convincing examples of aberrant glycans associated with cancer have come about from glycosylation analyses. Most studies have been carried out to identify changes in serum glycan profiles or through the isolation and identification of glycoproteins that contain these irregular glycan structures. In a majority of cancers the fucosylation and sialylation expression are found to be significantly modified. Therefore, these aberrations in glycan structures can be utilized as targets to improve existing cancer biomarkers.

General significance

The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. Furthermore, the high-throughput and reproducible nature of the chromatography platform have highlighted extensive applications in biomarker discovery and allowed integration of glycomics with other -omics fields, such as proteomics and genomics, making systems glycobiology a reality. This article is part of a Special Issue entitled Glycoproteomics.     

Novel cinnamaldehyde-based aspirin derivatives for the treatment of colorectal cancer

Colorectal cancer (CRC) is a leading cause of mortality worldwide. Current treatments of CRC involve anti-cancer agents with relatively good efficacy but unselectively target both cancer and non-cancer cells. Thus, there is a need to discover and develop novel CRC therapeutics that have potent anti-cancer effects, but show reduced off-target cell effects. Here, a novel series of cinnamaldehyde-based aspirin derivatives were designed and synthesized. Biological evaluation indicated that the most active compound 1f exhibited more than 10-fold increase in the anti-proliferation efficacy in HCT-8 cells compared to the parent compounds. Its effects were similarly reproduced in another CRC cell line, DLD-1, but with 7- to 11-fold less inhibitory activity in non-tumorigenic colon cells. Flow cytometry analysis showed that 1f induced cell cycle arrest and apoptosis, which was further validated with immunoblot analysis of the relative protein levels of cleaved caspase 3 and PARP as well as the ROS production in CRC cells. More so, 1f significantly inhibited the growth of implanted CRC in vivo in mouse xenograft model. Taken together, our results show that cinnamaldehyde-based aspirin derivatives such as 1f show promise as novel anti-CRC agent for further pharmaceutical development.     

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review

BackgroundBreast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis.MethodRelevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and (“HER2” or “Luminal A” or “Luminal B” or “TNBC”) and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses.ResultA total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient.ConclusionThe MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.