Exploring the role of molecular biomarkers as a potential weapon against gastric cancer: a review of the literature

Gastric cancer(GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging Ⅱ-Ⅳ. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.

Cyanidin 3-glucoside modulated cell cycle progression in liver precancerous lesion,in vivo study

BACKGROUND Cyanidin-3-O-glucoside(cyan)exhibits antioxidant and anticancer properties.The cell cycle proteins and antimitotic drugs might be promising therapeutic targets in hepatocellular carcinoma.AIM To investigate the effect of cyan administration on cell cycle in hepatic precancerous lesion(PCL)induced by diethylnitrosamine/2-acetylaminofluorene(DEN/2-AAF)in Wistar rats.METHODS In vivo,DEN/2-AAF-induced hepatic PCL,rats were treated with three doses of cyan(10,15,and 20 mg/kg/d,for four consecutive days per week for 16 wk).Blood and liver tissue samples were collected for measurement of the followings;alpha fetoprotein(AFP)liver function and RNA panel differential expression was evaluated via real time polymerase chain reaction.Histopathological examination of liver sections stained with H&E and immunohistochemical study using glutathione S-transferase placental(GSTP)and proliferating cell nuclear antigen(PCNA)antibodies were assessed.RESULTS Cyan administration mitigated the effect of DEN/2-AFF induced PCL,decreased AFP levels,and improved liver function.Remarkably,treatment with cyan dose dependently decreased the long non-coding RNA MALAT1 and tubulin gamma 1 mRNA expressions and increased the levels of miR-125b,all of which are involved in cell cycle and mitotic spindle assembly.Of note,cyan decreased GSTP foci percent area and PCNA positively stained nuclei.CONCLUSION Our results indicated that cyan could be used as a potential therapeutic agent to inhibit liver carcinogenesis in rat model via modulation of cell cycle.

New stem cell autophagy surrogate diagnostic biomarkers in earlystage hepatocellular carcinoma in Egypt:A pilot study

BACKGROUND Stem cell autophagy disruption is responsible for the development of hepatocellular carcinoma(HCC).Many non-coding RNAs are linked to the activation and inhibition of certain genes.The SQSTM1 gene controls stem cell autophagy as shown in previous studies.The upregulation of SQSTM1 is associated with the inhibition of autophagy in cancerous stem cells in patients with HCC.AIM To determine whether serum microRNA,hsa-miR-519d,is linked to SQSTM1 gene and whether they could be used as diagnostic biomarkers for early-stage HCC.METHODS In silico analysis was performed to determine the most correlated genes of autophagy with microRNAs.SQSTM1 and hsa-miR-519d were validated through this pilot clinical study.This study included 50 Egyptian participants,who were classified into three subgroups:Group 1 included 34 patients with early-stage HCC,Group 2 included 11 patients with chronic liver disease,and Group 3(control)included 5 healthy subjects.All patients were subjected to full laboratory investigations,including viral markers and alpha-fetoprotein(AFP),abdominal ultrasound,and clinical assessment with the Child–Pugh score calculation.Besides,the patients with HCC underwent triphasic computed tomography with contrast to diagnose and determine the tumor site,size,and number.Quantitative real-time polymerase chain reaction was used to assess hsa-miR-519d-3p and SQSTM1 in the serum of all the study participants.RESULTS Hsa-miR-519d-3p was significantly upregulated in patients with HCC compared with those with chronic liver disease and healthy subjects with an area under the curve(AUC)of 0.939,with cutoff value 8.34,sensitivity of 91.2%,and specificity of 81.8%.SQSTM1 was upregulated with an AUC of 0.995,with cutoff value 7.89,sensitivity of 97.1%,and specificity of 100%.AFP significantly increased in patients with HCC with an AUC of 0.794,with cutoff value 7.30 ng/mL,sensitivity of 76.5%,and specificity of 72.7%.CONCLUSION This study is the first to show a direct relation between SQSTM1 and hsa-miR-519d-3p;they are both upregulated in HCC.Thus,they could be used as surrogate diagnostic markers for stem cell autophagy disturbance in early-stage HCC.

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

Integrated technologies in the post-genomic era for discovery of bladder cancer urinary markers

The incidence of bladder cancer(BC) continues to rise with high recurrence and mortality rate, especially in the past three decades. The development of accurate and successful BC treatment relies mainly on early diagnosis. BC is a heterogeneous disease reflected by the presence of many potential biomarkers associated with different disease phenotypes. Nowadays, cystoscopy and urinary cytology are considered the gold standard diagnostic tools for BC. There are many limitations to cystoscopy including being invasive, labor-intensive and carcinoma in situ of the bladder may easily be missed. Urinary cytology is still a noninvasive technique with high accuracy in high-grade BC with a median sensitivity of 35%. Furthermore, the need for a sensitive, specific, non invasive, easily accessible BC biomarker is a major clinical need. The field of urinary BC biomarkers discovery is still a rapidly evolving discipline in which more recent technologies are evaluated and often optimized if they are not clinically significant to the urologists. Most of the current strategies for BC urinary biomarker detection depend on integration of information gleaned from the fields of genomics, transcriptomics, proteomics, epigenetics, metabolomics and bionanotechnology. Effort is currently being made to identify the most potentially beneficial urinary biomarkers. The purpose of this review is to summarize and explore the efficacy of gathering the information revealed from the cooperation of different omic strategies that paves the way towards various urinary markers discovery for screening, diagnosis and prognosis of human BC.