Risk factors of missed early gastric cancer in endoscopic resected population: a retrospective, case-control study.

BACKGROUND: Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. METHODS: This retrospective, case-control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. RESULTS: A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95% CI 0.27-0.74, P = 0.002) and invasion depth of submucosa (OR 0.26, 95% CI 0.10-0.69, P = 0.007) were negatively associated with MEGC. Use of sedation (OR 0.32, 95% CI 0.20-0.52, P < 0.001) and longer observation time (OR 0.60, 95% CI 0.37-0.96, P = 0.034) exhibited protective effect on MEGC. CONCLUSIONS: Smaller and more superficial EGC lesions are more susceptible to misdiagnosis. The use of sedation and prolonged observation time during EGD could help reduce the occurrence of MEGC.

Comparison of clinical and pathological features between early-stage gastric-type and intestinal-type differentiated adenocarcinoma: a retrospective study.

BACKGROUND: The clinicopathological features and endoscopic characteristics under magnifying endoscopy with narrow band imaging (ME-NBI) between early-stage gastric-type differentiated adenocarcinoma (GDA) and intestinal-type differentiated adenocarcinoma (IDA) remain controversial. METHODS: Early gastric adenocarcinomas that underwent endoscopic submucosal dissection (ESD) in Nanjing Drum Tower Hospital between August 2017 and August 2021 were included in the present study. GDA cases and IDA cases were selected based on morphology and immunohistochemistry staining of CD10, MUC2, MUC5AC, and MUC6. Clinicopathological data and endoscopic findings in ME-NBI were compared between GDAs and IDAs. RESULTS: The mucin phenotypes of 657 gastric cancers were gastric (n = 307), intestinal (n = 109), mixed (n = 181) and unclassified (n = 60). No significant difference was observed in terms of gender, age, tumor size, gross type, tumor location, background mucosa, lymphatic invasion, and vascular invasion between patients with GDA and IDA. GDA cases were associated with deeper invasion than IDA cases (p = 0.007). In ME-NBI, GDAs were more likely to exhibit an intralobular loop patten, whereas IDAs were more likely to exhibit a fine network pattern. In addition, the proportion of none-curative resection in GDAs was significantly higher than that in IDAs (p = 0.007). CONCLUSION: The mucin phenotype of differentiated early gastric adenocarcinoma has clinical significance. GDA was associated with less endoscopically resectability than IDA.

Risk factors of perforation in gastric stromal tumors during endoscopic resection: a retrospective case-control study.

BACKGROUND AND AIMS: Perforation is a common complication during endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) associated with secondary infections, sepsis, hospitalization time and cost. However, the risk factors of perforation remain controversial. This study aimed to investigate the risk factors for perforation during ER of gGISTs. METHODS: This retrospective case-control study included consecutive patients with gGISTs who underwent ER between June 2009 and November 2021 at the Nanjing Drum Tower Hospital. Univariate and multivariate analyses were performed to investigate the risk factors for perforation. Sensitivity analyses with propensity scoring (PS) were performed to evaluate the stability of the independent effects. RESULTS: In total, 422 patients with gGISTs were included. The following factors were associated with perforation during ER: in the non-intraluminal growth patterns (all confounders adjusted odds ratio [aOR]: 5.39, 95% CI 2.99-9.72, P < 0.001), in the gastric fundus (aOR 2.25, 95% CI 1.40-3.60, P = 0.007), sized ≥ 2 cm (aOR 1.70, 95% CI 1.04-2.77, P = 0.035), in the lesser curvature (aOR 0.12, 95% CI 0.05-0.27, P < 0.001), and in the gastric cardia (aOR 0.13, 95% CI 0.04-0.50, P = 0.003). The PS analysis confirmed the stable independent effects of these identified risk factors. CONCLUSIONS: ERs of gGISTs in non-intraluminal growth patterns, in the gastric fundus, and with larger tumor size were independent risk factors for perforation. While tumors in the lesser curvature or gastric cardia were independent protective factor for perforation.

A deep learning-based model improves diagnosis of early gastric cancer under narrow band imaging endoscopy.

BACKGROUND: Diagnosis of early gastric cancer (EGC) under narrow band imaging endoscopy (NBI) is dependent on expertise and skills. We aimed to elucidate whether artificial intelligence (AI) could diagnose EGC under NBI and evaluate the diagnostic assistance of the AI system. METHODS: In this retrospective diagnostic study, 21,785 NBI images and 20 videos from five centers were divided into a training dataset (13,151 images, 810 patients), an internal validation dataset (7057 images, 283 patients), four external validation datasets (1577 images, 147 patients), and a video validation dataset (20 videos, 20 patients). All the images were labeled manually and used to train an AI system using You look only once v3 (YOLOv3). Next, the diagnostic performance of the AI system and endoscopists were compared and the diagnostic assistance of the AI system was assessed. The accuracy, sensitivity, specificity, and AUC were primary outcomes. RESULTS: The AI system diagnosed EGCs on validation datasets with AUCs of 0.888-0.951 and diagnosed all the EGCs (100.0%) in video dataset. The AI system achieved better diagnostic performance (accuracy, 93.2%, 95% CI, 90.0-94.9%) than senior (85.9%, 95% CI, 84.2-87.4%) and junior (79.5%, 95% CI, 77.8-81.0%) endoscopists. The AI system significantly enhanced the performance of endoscopists in senior (89.4%, 95% CI, 87.9-90.7%) and junior (84.9%, 95% CI, 83.4-86.3%) endoscopists. CONCLUSION: The NBI AI system outperformed the endoscopists and exerted potential assistant impact in EGC identification. Prospective validations are needed to evaluate the clinical reinforce of the system in real clinical practice.

Contributions of HOTAIR polymorphisms to the susceptibility of cancer.

OBJECTIVE: Hox transcript antisense intergenic RNA (HOTAIR), a lncRNA, functions as a critical regulator in cancer development. A plenty of case-control studies were conducted to assess the actual relationship of HOTAIR gene generic variants on cancer susceptibility, yet conflicting conclusions remain. Herein, we carried out this up-to-date meta-analysis to get a better understanding of such relationship by incorporating all eligible case-control studies. MATERIALS AND METHODS: Six widely investigated polymorphisms were included in this meta-analysis: rs920778, rs4759314, rs7958904, rs874945, rs1899663, and rs12826786. We retrieved relevant studies from databases PubMed, EMBASE, Medline, CNKI and Wanfang update to June 2020. We applied odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the relationship strengths. RESULTS: Our findings indicate that rs920778, rs4759314, rs874945, rs12826786 polymorphism significantly increased with susceptibility to overall cancer. However, rs7958904, rs1899663 under any five genetic models could not impact susceptibility to overall cancer. Furthermore, altered cancer risk was detected when the data were stratified by cancer type, ethnicity, the source of controls, and HWE in all the SNPs. CONCLUSIONS: These findings of the meta-analysis suggest that HOTAIR polymorphisms may predispose to cancer susceptibility.

Outcome of a novel modified endoscopic papillectomy for duodenal major papilla adenoma.

BACKGROUND AND AIMS: In recent years, with the development of endoscopic techniques, endoscopic resection is widely used for duodenal papillary adenomas, but conventional endoscopic resection has a high rate of incomplete resection and recurrence. On this basis, we have employed a novel modified endoscopic papillectomy (ESP). In this study, we evaluated the feasibility and advantages of this ESP for the treatment of duodenal major papilla adenoma. METHODS: A total of 56 patients with duodenal major papilla adenoma confirmed by endoscopic ultrasonography, intraluminal ultrasound and gastroscopic biopsy from October 2007 to June 2017 were collected in the Department of Gastroenterology, Nanjing Drum Tower Hospital. The diameter of the adenoma ranged from 1.41 to 2.02 cm. 16 cases were given the conventional method and 40 cases underwent the modified ESP procedure in which a small incision was made by cutting current when anchoring the snare tip on the distal side of the adenoma. RESULTS: En bloc resection rate was significantly higher in the modified group (100%, 40/40) than that in the conventional group (81.3%, 13/16; P = 0.02). However, no significance was seen between the modified group and the conventional group in complete resection rate (92.5%, 37/40 vs 93.8%, 15/16; P = 1.00). There was no significant difference in the number and difficulty of postoperative pancreatic and biliary stents placement between the two groups (P = 0.20). Total bleeding occurrence was much lower in the modified group (37.5%, 15/40 vs 87.5%, 14/16; P = 0.001), and no significant differences were found in other short-term complications and the 3, 6, 12 and 24 months recurrences rate between the conventional and modified ESP groups. CONCLUSIONS: The modified ESP improves the treatment outcome of duodenal major papilla adenoma with higher en bloc resection rate and lowering bleeding rate.

Classification of the cystic duct patterns and endoscopic transpapillary cannulation of the gallbladder to prevent post-ERCP cholecystitis.

BACKGROUND: Endoscopic transpapillary cannulation of the gallbladder is useful but challenging. This study aimed to investigate cystic duct anatomy patterns, which may guide cystic duct cannulation. METHODS: A total of 226 patients who underwent endoscopic transpapillary cannulation of the gallbladder were analyzed retrospectively. RESULTS: According to the cystic duct take-off, 226 cystic duct patterns were divided into 3 patterns: Type I (193, 85.4%), located on the right and angled up; Type II (7, 3.1%), located on the right and angled down; and Type III (26, 11.5%), located on the left and angled up. Type I was further divided into three subtypes: Line type, S type (S1, not surrounding the common bile duct; S2, surrounding the common bile duct), and α type (α1, forward α; α2, reverse α). Types I and III cystic ducts were easier to be cannulated with a higher success rate (85.1 and 86.4%, respectively) compared with Type II cystic duct (75%) despite no statistically significant difference. The reasons for the failure of gallbladder cannulation included invisible cyst duct take-off, severe cyst duct stenosis, impacted stones in cyst duct or neck of the gallbladder, sharply angled cyst duct, and markedly dilated cyst duct with the tortuous valves of Heister. CONCLUSION: Classification of cystic duct patterns was helpful in guiding endoscopic transpapillary gallbladder cannulation.

Risk factors for post-ERCP cholecystitis: a single-center retrospective study.

BACKGROUND: The risk factors for post-ERCP cholecystitis (PEC) have not been characterized. Hence, this study aimed to identify the potential risk factors for PEC. METHODS: The medical records of 4238 patients undergoing the first ERCP in a single center from January 2012 to December 2016 were analyzed in this study. A multivariate analysis was used to identify the risk factors. RESULTS: This study included 2672 patients who met the enrollment criteria. Of these, 36 patients (incidence rate of 1.35%) developed PEC within 2 weeks of the procedure. Univariate and multivariate analyses identified the following factors associated with PEC: history of acute pancreatitis [odds ratio (OR) = 2.60; 95% confidence interval (CI): 1.29-5.23], history of chronic cholecystitis (OR = 8.47; 95% CI: 2.54-28.24), gallbladder opacification (OR = 2.79; 95% CI: 1.37-5.70), biliary duct metallic stent placement (OR = 3.66; 95% CI: 1.78-7.54), and high leukocyte count before ERCP (OR = 1.10; 95% CI: 1.04-1.17). The prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.80-0.91). A prognostic nomogram was developed using the aforementioned variables to estimate the probability of PEC. CONCLUSIONS: The risk factors, including the history of acute pancreatitis, history of chronic cholecystitis, gallbladder opacification, biliary duct metallic stent placement, and high leucocyte counts before ERCP, increased the occurrence of PEC and were positive predictors for PEC. The constructed nomogram was used to estimate the risk of PEC, guiding the implementation of prophylactic measures to prevent PEC in clinical practice.

Caspase inhibitor zVAD-fmk protects against acute pancreatitis-associated lung injury via inhibiting inflammation and apoptosis.

BACKGROUND/OBJECTIVES: Pulmonary apoptosis is an important pathogenic mechanism of acute lung injury induced by many factors. This study aims to investigate whether the caspase inhibitor zVAD-fmk has a protective effect against lung injury in the severe acute pancreatitis model (SAP) in rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into Sham, SAP, and SAP + zVAD-fmk groups. The SAP model was established by injection of 5% sodium taurocholate into the pancreatic duct. Animals were sacrificed at 3 h, 6 h, 12 h, and 24 h after operation and then HE staining analysis was performed to assess the lung injury. ELISA was used to detect the activity of myeloperoxidase (MPO) and the concentrations of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß). Western blotting was used to detect the expression of cleaved caspase-3 in the lung tissues. RESULTS: Rats in SAP group showed obvious lung injury through pathologic examination. Pretreatment with zVAD-fmk significantly inhibited a post-SAP increase in the activation of MPO, TNF-α, IL-1ß, and caspase-3, and decreased lung injury induced by SAP as determined by the pathologic score. CONCLUSION: Our results suggest that apoptosis plays an important role in acute pancreatitis-associated lung injury (APALI), and inhibition of caspase activity may represent a new therapeutic approach for the treatment of APALI.

Downregulation of FOXP3 inhibits invasion and immune escape in cholangiocarcinoma.

FOXP3 is known as a master control of regulatory T cells with recently studies indicating its expression in several tumor cells. In order to study the precise role of FOXP3 in cholangiocarcinoma, FOXP3 was knocked down in cholangiocarcinoma cell lines. Down regulation of FOXP3 inhibits tumor cell invasion by reducing the quantity of MMP-9 and MMP-2. With FOXP3 knocking down, IL-10 and TGF-ß1 secreted by cancer cells diminishes and the cell survival of T cells is significant up-regulation. These results suggest that FOXP3 plays an important role in tumor malignant phenotype, especially the invasion and immune escape.

Gemcitabine sensitizes pancreatic cancer cells to the CTLs antitumor response induced by BCG-stimulated dendritic cells via a Fas-dependent pathway.

BACKGROUND/OBJECTIVES: There are increasing evidences suggesting that chemotherapeutic agents can enhance the cytotoxic T lymphocytes (CTLs) antitumor effect, but the precise mechanism is not fully explained. This study aims to investigate whether gemcitabine (GEM) can sensitize pancreatic cancer cells to the CTLs antitumor response, and explore the potential mechanism. METHODS: Cell counting kit-8 assays (CCK-8) were performed to determine the tumor cell proliferation. Flow cytometric analysis was conducted to analyze maturation of DCs and the expression of Fas. An Annexin V FITC Apoptosis Detection Kit was performed to detect tumor cell apoptosis. CytoTox 96 Nonradioactive Cytotoxicity assays were used to determine T cell-mediated tumor cell lysis. RESULTS: First, it was demonstrated that Bacillus Calmette Guérin (BCG) could be used to induce effective CTLs antitumor response. Then, GEM inhibited the growth of SW1990 cells, induced apoptosis and upregulated the Fas expression even at a low concentration. When antagonistic anti-Fas mAb ZB4 was preincubated with GEM-treated SW1990 cells, the lysis induced by CTLs was reduced. Moreover, agonistic anti-Fas mAb CH11 induced more apoptosis of GEM-treated SW1990 cells. CONCLUSION: Our results show that GEM sensitizes pancreatic cancer cells to the CTLs antitumor response, and the sensitization is associated with upregulation of Fas on pancreatic cancer cells.

Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1.

BACKGROUND: Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. METHODS: CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. RESULTS: Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. CONCLUSIONS: Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA.

Comparison of Modified Cap-Assisted Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection in Treating Intraluminal Gastric Gastrointestinal Stromal Tumor (≤20 mm).

INTRODUCTION: A modified cap-assisted endoscopic mucosal resection (mEMR-C), introduced in this study, was a novel variation of the standard EMR. We aimed to compare the outcomes of mEMR-C and endoscopic submucosal dissection (ESD) for the treatment of small (≤20 mm) intraluminal gastric gastrointestinal stromal tumors (gGISTs). METHODS: This retrospective study included 43 patients who underwent mEMR-C and 156 patients who received ESD at Nanjing Drum Tower Hospital. Baseline characteristics, adverse events, and clinical outcomes were compared between the 2 groups. Univariate and multivariable analyses were conducted to adjust for confounders. After propensity score matching using sex, year, location, and tumor size, outcomes were compared with 41 patients in each group. RESULTS: A total of 199 patients underwent endoscopic resection and the en bloc resection rate was 100%. The complete resection rate was comparable in both groups ( P = 1.000). Approximately 9.5% of all patients had a positive margin. There was no significant difference in positive margin for patients undergoing mEMR-C or ESD (9.3% vs 9.6%, P = 1.000). No difference in adverse events in both groups ( P = 0.724). The mEMR-C was associated with shorter operation time and lower cost than the ESD. Recurrence was reported in 2 patients at 1 and 5 years after ESD during a median follow-up of 62 months. No metastasis and disease-related death were identified in both groups. Propensity score matching analysis revealed similar results. DISCUSSION: The mEMR-C was found to be the preferable technique for small (≤20 mm) intraluminal gGISTs with shorter operation time and lower cost as compared with ESD.

Erratum: Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.

[This corrects the article on p. 546 in vol. 9, PMID: 30949409.].

Loss of LncRNA DUXAP8 synergistically enhanced sorafenib induced ferroptosis in hepatocellular carcinoma via SLC7A11 de-palmitoylation.

BACKGROUND: Ferroptosis is an important iron-dependent form of cell death in hepatocellular carcinoma (HCC). Sorafenib, a potent ferroptosis inducer, is used to treat advanced HCC but its efficacy is limited by the development of drug resistance. METHODS: The effects of DUXAP8 expression on HCC progression were evaluated by TCGA database, Kaplan-Meier analysis, and in situ hybridization analysis. Sorafenib resistant HCC cell lines were modeled in vitro to study the regulation of DUXAP8 on ferroptosis in HCC induced by sorafenib. We used RNA pull-down, immunofluorescence assays, acyl-biotinyl exchange assay and mass spectrometry analysis to assess the molecular mechanism of ferroptosis regulation by DUXAP8. Syngeneic subcutaneous and orthotopic CDX models were used to assess whether DUXAP8 inhibition improves HCC in vivo. RESULTS: LncRNA DUXAP8, which is highly expressed in liver cancer and associated with poor prognosis, contributes to sorafenib resistance through suppression of ferroptosis. In vitro tests revealed that DUXAP8 reduced the sensitivity of HCC to sorafenib-induced ferroptosis by acting on SLC7A11, a subunit of the amino acid antiporter system xc-. DUXAP8 facilitates SLC7A11 palmitoylation and impedes its lysosomal degradation, thereby enhancing SLC7A11 action and suppressing ferroptosis. RNA pull-down and immunofluorescence assays confirmed that DUXAP8 decreased membrane translocation and promoted sorting of de-palmitoylated SLC7A11 to lysosomes by binding of DUXAP8 to SLC7A11. In addition, mass spectrometric analysis found that the Cys414 residue of SLC7A11 might be the predominant mutant site responsible for molecular masking of SLC7A11 lysosomal sorting. Further, the antitumor effect of DUXAP8 knockdown was verified in orthotopic and subcutaneous CDX models. CONCLUSIONS: Our findings suggest that a novel translational strategy combining sorafenib with DUXAP8 silencing to overcome drug resistance may improve treatment efficacy in patients with advanced HCC.

Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of post-ERCP pancreatitis (PEP) is still controversial. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of NSAIDs for PEP prophylaxis. DESIGN: We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies published updated to June 2012. SETTING: Meta-analysis. PATIENTS: Patients undergoing ERCP. INTERVENTIONS: NSAIDs use for the prevention of PEP. MAIN OUTCOME MEASUREMENTS: Overall incidence of PEP, incidence of moderate to severe PEP, and adverse events. RESULTS: Ten RCTs involving 2269 patients were included. Meta-analysis showed that NSAID use decreased the overall incidence of PEP (risk ratio [RR], 0.57; 95% CI, 0.38-0.86; P = .007). The absolute risk reduction was 5.9%. The number needed to treat was 17. Heterogeneity among the studies was substantial. However, after removing the main source of heterogeneity, the prophylactic efficacy was similar (RR, 0.53; 95% CI, 0.41-0.68; P < .001). NSAID use also decreased the incidence of moderate to severe PEP (RR 0.46; 95% CI, 0.28-0.75; P = .002). The absolute risk reduction was 3.0%. The number needed to treat was 34. No differences of the adverse events attributable to NSAIDs were observed. LIMITATIONS: Inclusion of low-quality studies, different type and route of administration of the NSAIDs, study heterogeneity, inconsistent use of pancreatic stenting. CONCLUSIONS: Prophylactic use of NSAIDs reduces the incidence and severity of PEP.

Establishment and Characterization of a New Human Intrahepatic Cholangiocarcinoma Cell Line LIV27.

Cholangiocarcinoma (CCA) is a highly lethal cancer arising from the biliary tract epithelium. The cancer biology of this neoplasm is not well understood. To date, only a few CCA cell lines have been reported, which were mostly developed from Asian patients. In this study, we report and characterize a new intrahepatic CCA cell line, LIV27, derived from a surgically resected tumor in a 67-year-old Caucasian woman with primary sclerosing cholangitis (PSC). LIV27 cells grow well in collagen-coated flasks or plates with a doubling time of 57.8 h at passage 14. LIV27 cells have high tumorigenicity in nude mice and stain positive for CK7 and CK19, markers that differentiate CCA from hepatocellular carcinoma. Karyotype analysis showed that LIV27 is aneuploid. We established a single-locus short tandem repeat profile for the LIV27 cell line. This newly established cell line will be a useful model for studying the molecular pathogenesis of, and developing novel therapies for, cholangiocarcinoma.

Circulating microRNAs: potential biomarkers for cancer.

Cancer is the leading cause of death in the world. Development of minimally invasive biomarkers for early detection of cancer is urgently needed to reduce high morbidity and mortality associated with malignancy. MicroRNAs (miRNAs) are small regulatory RNAs that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. Recently, miRNAs were found to be dysregulated in a variety of diseases including cancer. Emerging evidence suggests that miRNAs are involved in tumor initiation and progression. Together, the different expression profiles of miRNAs in cancer, and the stability of circulating miRNAs, make them new potentially clinical biomarkers for cancer diagnosis, classification, therapeutic decisions, and prognosis.