Gut microbiota in patients after surgical treatment for colorectal cancer

Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.     

结直肠癌无创筛查技术研究进展

结直肠癌和高危腺瘤的早期诊断及治疗,能够大大降低其死亡率。因而,在临床普及结直肠癌筛查有助于遏制该疾病的危害。目前,结肠镜检查是结直肠癌诊断的金标准,但该方法需要肠道准备,且具有侵入性,易造成肠道穿孔等缺点,导致患者依从性差,不利于其作为大规模筛查技术推广实施。近年来非侵入性的结直肠癌诊断方法发展迅速,这类方法主要通过检测粪便或血液样本中与结直肠癌发生相关的生物标志物,为结直肠癌的无创筛查提供了可能。但由于粪便、血液样本的成分复杂,对其中生物标志物的检测技术仍然在不断研究和完善中。本文分别从基于粪便样本和血液样本的检测技术两方面入手,探讨了近年来结直肠癌无创筛查技术的研究进展。     

肠道菌群及其代谢产物与结肠腺瘤性息肉相关性的研究进展

结肠癌（colorectal cancer,CRC）是常见的消化道恶性肿瘤,其发病率和病死率都极高。从结肠息肉发展到结肠癌一般需要10～15年,且大多遵循息肉‒腺瘤‒癌症的发展过程,结肠腺瘤性息肉（colorectal adenomatous polyps,CAP）被认为是结肠癌的癌前病变。有研究显示肠道菌群的改变与肠道腺瘤性息肉样变及癌症的发生发展有密切的相关性。根据肠道菌群在不同病理状态下的富集程度,可以进一步分析其与结肠病变之间的关系。本文就肠道菌群的构成,CAP患者粪便和腺瘤组织中肠道菌群富集的改变,以及肠道菌群代谢产物对CAP患者的影响等内容进行综述,为结肠腺瘤性息肉的早期诊断和治疗提供依据。     

Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no?=?35), adenomas (no?=?51), and neoplasm free controls (no?=?101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p?<?0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p?<?0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

     

Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma

Colorectal cancer(CRC)and hepatocellular carcinoma(HCC)are the second and third most common causes of death by cancer,respectively.The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol,smoking,diet,obesity and diabetes.Patho-logical changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC.However,the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and envi-ronmental factors.in this review,we examine the chan-ges that occur in the composition of the gut microbiota across the stages of the HCC and CRC.Based on the idea that the gut microblota are an additional"lifeline"and contribute to the tumor microenvironment,we can observe from previously published literature how the microbiota can cause a shift in the balance from normal→ inflammation → diminished inflammation from early to later disease stages.This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment.The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.     

Serum-based protein biomarkers for detection of lung cancer

Lung cancer is one of the most common cancers in terms of both incidence and mortality.The major reasons for the increasing number of deaths from lung cancer are late detection and lack of effective therapies. To improve our understanding of lung cancer biology, there is urgent need for blood-based, non-invasive molecular tests to assist in its detection in a cost-effective manner at an early stage when curative interventions are still possible. Recent advances in proteomic technology have provided extensive, high throughput analytical tools for identification, characterization and functional studies of proteomes. Changes in protein expression patterns in response to stimuli can serve as indicators or biomarkers of biological and pathological processes as well as physiological and pharmacological responses to drug treatment, thus aiding in early diagnosis and prognosis of disease. However, only a few biomarkers have been approved by the FDA to date for screening and diagnostic purposes. This review provides a brief overview of currently available proteomic techniques, their applications and limitations and the current state of knowledge about important serum biomarkers in lung cancer and their potential value as prognostic and diagnostic tools.     

Plasma miR-601 and miR-760 Are Novel Biomarkers for the Early Detection of Colorectal Cancer

Background

Colorectal cancer (CRC) is a major cause of death worldwide. Sensitive, non-invasive diagnostic screen methods are urgently needed to improve its survival rates. Stable circulating microRNA offers unique opportunities for the early diagnosis of several diseases, including cancers. Our aim has been to find new plasma miRNAs that can be used as biomarkers for the detection of CRC.

Methodology/Principal Findings

According to the results of miRNA profiling performed on pooling plasma samples form 10 CRC patients or 10 healthy controls, a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188-3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa-let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large scale validation by qRT-PCR performed on another 191 independent individuals (90 CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels of plasma miR-601 and miR-760 were significantly decreased in colorectal neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC curve analysis showed that plasma miR-601 and miR-760 were of significant diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1% specificity in discriminating advanced adenomas from normal controls.

Conclusions/Significance

Plasma miR-601 and miR-760 can potentially serve as promising non-invasive biomarkers for the early detection of CRC.     

Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer

Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.     

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn''s disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1–V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.     

Blood-Based Protein Biomarker Panel for the Detection of Colorectal Cancer

Background

The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test.

Principal Findings

In two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2).

Conclusions

Due to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test.     

The role of exosomes in colorectal cancer disease progression and response to therapy

Colorectal cancer (CRC) is the second leading cause of cancer mortality in both men and women worldwide. Survival of patients is significantly associated with disease stage at diagnosis. Recent studies highlighted a role of exosomes in CRC development and progression, thus raising the interest on these nanosized vesicular structures as possible biomarkers. Exosomes contain a large variety of molecules, including proteins, lipids and nucleic acids, that are exchanged between cells either within tumor microenvironment or at distant sites from the primary tumor, where they prepare a suitable soil for tumor metastases. The present review summarizes the principal effects of exosomes on CRC development, progression, and provides an update of the most recent findings on the use of exosomal molecules as diagnostic, prognostic and predictive biomarkers in CRC.     

The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5-15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.     

Therapeutic potential of melatonin in colorectal cancer: Focus on lipid metabolism and gut microbiota

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. The occurrence and development of CRC are complicated processes. Obesity and dysbacteriosis have been increasingly regarded as the main risk factors for CRC. Understanding the etiology of CRC from multiple perspectives is conducive to screening for some potential drugs or new treatment strategies to limit the serious side effects of conventional treatment and prolong the survival of CRC patients. Melatonin, a natural indoleamine, is mainly produced by the pineal gland, but it is also abundant in other tissues, including the gastrointestinal tract, retina, testes, lymphocytes, and Harder's glands. Melatonin could participate in lipid metabolism by regulating adipogenesis and lipolysis. Additionally, many studies have focused on the potential beneficial effects of melatonin in CRC, such as promotion of apoptosis; inhibition of cell proliferation, migration, and invasion; antioxidant activity; and immune regulation. Meaningfully, gut microbiota is the main determinant of all aspects of health and disease (including obesity and tumorigenesis). The gut microbiota is of great significance for understanding the relationship between obesity and increased risk of CRC. Although the current understanding of how the melatonin-mediated gut microbiota coordinates a variety of physiological and pathological activities is fairly comprehensive, there are still many unknown topics to be explored in the face of a complex nutritional status and a changeable microbiota. This review summarizes the potential links among melatonin, lipid metabolism, gut microbiota, and CRC to promote the development of melatonin as a preventive and therapeutic agent for CRC.     

Noninvasive molecular biomarkers for the detection of colorectal cancer

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, noninvasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.     

lncRNA KIAA0125 functions as a tumor suppressor modulating growth and metastasis of colorectal cancer via Wnt/β‐catenin pathway

Colorectal cancer (CRC) is the third most common cancer in all races worldwide in recent years. The survival of the CRC patients is mostly affected by the stage of the disease at the time of diagnosis. Thus, the current challenge is to find sensitive and reliable biomarkers in early screening of CRC. Recently, emerging evidence has shown that long non‐coding RNAs (lncRNAs) may play crucial roles in tumorigenesis. In this study, we found that lncRNA KIAA0125 was downregulated in colorectal tissues and cells. The functional study demonstrated that overexpression of KIAA0125 suppressed cell proliferation, migration, and invasion whereas the reversal effects were seen in silencing experiment. Besides, KIAA0125 inhibited epithelial–mesenchymal transition through Wnt/β‐catenin signaling in CRC. Our findings suggested that KIAA0125 may act as an oncosupressor gene and could be considered as a potential diagnosis biomarker in CRC.     

脆弱拟杆菌在炎症性肠病、结直肠癌促进、调控及防治中的作用

近年来人们越来越重视肠道菌群在肠源性疾病的发生、发展及防治中所发挥的作用。脆弱拟杆菌(Bacteroides fragilis,BF)是定殖于人体肠道中的共生菌,对肠道健康有多种影响,是健康人群及腹泻、腹膜炎、腹内脓肿、败血症、炎症性肠病等临床病例最常见的肠道微生物。随着人们对脆弱拟杆菌的深入研究,发现脆弱拟杆菌与炎症性肠病(inflammatory bowel disease,IBD)、结直肠癌(colorectal cancer,CRC)有密切关系。通过对脆弱拟杆菌与IBD、CRC之间的关系进行综述,探究脆弱拟杆菌在IBD、CRC促进、调控及防治中的作用,为IBD、CRC的早期干预和治疗提供新思路,为开发基于脆弱拟杆菌的药物提供数据与思路。     

Proteomics for early detection of colorectal cancer: recent updates

Introduction: Colorectal cancer (CRC) is a common type of cancer with a relatively poor survival rate. The survival rate of patients could be improved if CRC is detected early. Biomarkers associated with early stages of tumor development might provide useful tools for the early diagnosis of colorectal cancer.

Areas covered: Online searches using PubMed and Google Scholar were performed using keywords and with a focus on recent proteomic studies. The aim of this review is to highlight the need for biomarkers to improve the detection rate of early CRC and provide an overview of proteomic technologies used for biomarker discovery and validation. This review will also discuss recent proteomic studies which focus on identifying biomarkers associated with the early stages of CRC development.

Expert commentary: A large number of CRC biomarkers are increasingly being identified by proteomics using diverse approaches. However, the clinical relevance and introduction of these markers into clinical practice cannot be determined without a robust validation process. The size of validation cohorts remains a major limitation in many biomarker studies.     

Exosomal surface protein markers in diagnosis of colorectal cancer

Colorectal cancer (CRC) is one of the most common primary malignancies. Early stages of the disease are asymptomatic in the majority of cases, leading to late detection and high mortality. Available noninvasive diagnostic techniques are limited in sensitivity and specificity, and designing new ones is still a pressing problem. Exosomes are membrane-derived microvesicles secreted into human biological fluids and provide a novel way to assess the course of an oncology disease. The review describes the repertoire of exosomal surface biomarkers found in the blood of CRC patients and the prospects of employing multiplexed tests for exosomal markers in early noninvasive diagnosis of cancer.     

The association of diet,gut microbiota and colorectal cancer: what we eat may imply what we get

Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies.Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increasedriskofdevelopingCRC.In conclusion, abalanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC.     

肠道菌群与microRNA的交互在促结直肠癌中的作用

结直肠癌是西方国家最常见的癌症之一,多数患者伴有肠道菌群的改变。有研究表明,肠道菌群通过microRNA调节宿主基因的表达,而宿主的microRNA同样调节菌群的生长和基因表达。因此,本文概述了肠道菌群与宿主microRNA相互作用的具体机制,以及这种交互作用在结直肠癌的发生、发展、治疗阶段的研究进展。为进一步深入研究肠道菌群与结直肠癌的关系提供理论基础。