Types Of Gastrointestinal Cancers Research Articles

Benefit of early-phase targeted, basket, and immune-based trials for patients with chemorefractory gastrointestinal (GI) cancers.

e15700 Background: Historically, phase I trials were designed to establish phase II tolerable doses of new drugs. Efficacy concerns were secondary. In the modern era of targeted and immune-based therapies, investigator and patient expectations of efficacy in such trials have increased. Patients (pts) who have exhausted standard treatment options often seek participation in phase I drug development or phase II basket studies, with hope for therapeutic benefit. We assessed the benefit to pts with chemorefractory GI cancers from investigational early drug development trials at our institution. Methods: We reviewed the referral records of our Early Drug Development and Immunotherapy Services to identify pts referred from our GI Oncology Service in 2018. As pts are typically not referred unless with performance status 0-1, and normal liver, renal, and marrow function, those requesting early phase studies but not meeting these criteria were excluded from this analysis. End points were enrollment on a trial, 3 and 6-month PFS, and tumor shrinkage. Results: Of 245 GI Oncology pts referred in 2018, 26 (11%) were accrued to a trial: 14 to immune-based (1 withdrew before treatment) and 12 to targeted (3 to phase II basket): median age 53 (range 23-76); 15 female. GI cancer types included: colon (7), pancreas (7), cholangiocarcinoma (4), rectal (3), and appendiceal, peritoneal mesothelioma, small bowel, unknown primary, and gastric (1). Most common reasons for non-accrual were lack of available treatment spots and failure to meet eligibility criteria for specific trials. Of 22 pts with adequate follow up at time of analysis, none achieved 6-month PFS; one (5%) met 3-month PFS with tumor growth below RECIST criteria at 3 months and came off study for progression at 4 months. No pts achieved any degree of tumor shrinkage while receiving trial drugs. Conclusions: Phase I and phase II basket options for chemorefractory GI cancers were limited relative to demand. Benefit from investigational treatment in this patient population was limited; expectations may be overstated. Further research is underway to evaluate pts’ expectations for therapeutic benefit from early phase targeted and immune-based trials.

Comparision Of BRAF V600E, COX–2 and p53 As Biomarkers For The Early Detection Of Colorectal Cancer

Colorectal cancer (CRC) is one of the most common types of gastrointestinal cancer. Almost two million new cases of CRC are diagnosed every year, making CRC the third most common cancer and the fourth most common cancer-associated cause of mortality in the world. The onset and development of CRC is induced by a combination of genetic and environmental factors including social, cultural and lifestyle factors. Age is considered as main risk factor for the colorectal cancer, there is remarkable increase past the fifth decade of life. Because of its high incidence and mortality rate worldwide, colorectal cancer (CRC) has become a global public health problem. Patients with CRC are typically asymptomatic and therefore it is difficult to diagnose disease until advanced stages, where the disease becomes incurable. Early diagnosis and therapy is able to decrease the risk of CRC in this asymptomatic population; however, early diagnosis of CRC remains a challenge in clinical practice. This review article was a comparative study and aims to explore the ability of the selected markers for early diagnosis of colorectal cancers for long term survival. Hence, identification of novel non-invasive diagnostic methods for early tumor detection in CRC is required. Screening of average-risk individuals can reduce CRC mortality by detecting cancer at an early curable stage. There is need for the implementation of new speci?c and more sensitive biomarkers in upcoming future which will improve diagnostic strategies and allowing clinicians to detect CRC cases in the earliest stages of the disease, to improve the prognosis of thousands of patients.

Physical Activity and Gastrointestinal Cancer Risk: A Review

Abstract Introduction: Western lifestyle characterized by increased consumption of red meat, fat, processed food, smoking, alcohol drinking, lower consumption of vegetables and physical inactivity has been associated with a higher gastrointestinal cancer risk. Digestive system cancers are diagnosed at late stages when they show poor response to treatment and are associated with a high mortality rate. Colorectal, gastric, esophageal and pancreatic cancers are among the most common cancers worldwide. Studies show that more than 50% of gastrointestinal cancers develop as a result of inappropriate lifestyle. An inverse association between physical activity and many chronic diseases has been proved so far. However, the association between physical activity and some gastrointestinal cancers is still controversial. This study was aimed to determine the association between physical activity and gastrointestinal cancers risk. Methods: We conducted a comprehensive search of English and Persian databases from February 2007 till December 2017, for studies investigating the association of physical activity and risk of gastrointestinal cancers. Finally, after reading full text of articles, 123 studies were included. Results: Physical activity can be helpful in reducing the risk of gastrointestinal cancer, especially colon and pancreatic cancers. The risk reduction is not similar for different types of gastrointestinal cancers and also among males and females. Conclusion: Different types of physical activity are associated with a lower risk of gastrointestinal cancer. However, it is unknown which type and intensity of physical activity are associated with a protective effect against gastro-intestinal cancer.

Trends in Mortality Rates for Gastrointestinal Cancers in Fars Province, Iran (2005-2015).

In Iran, cancers are the third leading cause of death, and gastrointestinal cancers are the primary cause of mortality among all the cancers. This study aimed to determine the trend of crude and age-standardized mortality rates (ASMR) for different types of gastrointestinal cancers over an 11-year period in Fars province (Iran). In this study, all the mortality data for gastrointestinal cancers were derived from the Electronic Death Registration System (EDRS) between 2005 and 2015. Subsequently, we calculated the crude and age-standardized mortality rates (ASMR) and their trends for different types of gastrointestinal cancers based on age groups and gender over the study period. A total of 6547 deaths from gastrointestinal cancers were identified, with an average age of 66.0 ± 16.4years. The crude and age-standardized mortality rates for gastrointestinal cancers were respectively 10.9 and 15.0 per 100,000 population in 2005 which significantly increased to 17.4 and 19.4 per 100,000 population in 2015 (P < 0.001). The ASMR for colon, pancreatic, and oral cancers showed an increasing trend; for small intestine cancers, a decreasing trend; and for esophageal, gastric, rectal, and hepatobiliary cancers displayed an almost constant trend. Our study shows a higher ASMR and an increasing trend of gastrointestinal cancers in Fars province. Prevention and early diagnosis programs with screening techniques should be implemented to control the mortality rate of gastrointestinal cancers in the future.

Anti-colorectal cancer effects of anti-p21Ras scFv delivered by the recombinant adenovirus KGHV500 and cytokine-induced killer cells

BackgroundColorectal cancer (CRC) is the most common type of gastrointestinal cancer. CRC gene therapy mediated by adenovirus holds great promise for the treatment of malignancies. However, intravenous delivery of adenovirus exhibits limited anti-tumor activity in vivo when used alone.MethodsIn this study, the antitumor activity of the recombinant adenovirus KGHV500 was assessed with the MTT, TUNEL, Matrigel invasion and cell migration assays. To enhance the intravenous delivery of KGHV500 in vivo, cytokine-induced killer (CIK) cells were used as a second vector to carry KGHV500. We explored whether CIK cells could carry the recombinant adenovirus KGHV500 containing the anti-p21Ras single chain fragment variable antibody (scFv) gene into tumors and enhance antitumor potency.ResultsOur results showed that KGHV500 exhibited significant antitumor activity in vitro. In the nude mouse SW480 tumor xenograft model, the combination of CIK cells with KGHV500 could induce higher antitumor activity against colorectal cancer in vivo than that induced by either CIK or KGHV500 alone. After seven days of treatment, adenovirus and scFv were detected in tumor tissue but were not detected in normal tissues by immunohistochemistry. Therefore, KGHV500 replicates in tumors and successfully expresses anti-p21Ras scFv in a colorectal cancer xenograft model.ConclusionsOur study provides a novel strategy for the treatment of colorectal cancer by combining CIK cells with the recombinant adenovirus KGHV500 which carried anti-p21 Ras scFv.

The Effect of Flubendazole on Adhesion and Migration in SW480 and SW620 Colon Cancer Cells.

Colon cancer is the most common type of gastrointestinal cancer. Despite advances during the last two decades, the efficacy of colorectal cancer treatment is still insufficient and new anticancer agents are necessary. In our study, colon cancer cells derived from a primary tumor (SW480) and lymph node metastasis (SW620) from the same patient were used and compared. The effect of flubendazole (FLU) on cell adhesion and migration was monitored using the x-CELLigence Real-Time Cell Analysis system. Expressions of molecules involved in adhesion and migration were analyzed using RT-PCR and western blot. Furthermore, RNA silencing of nuclear factor-κB in SW620 cells was used to determine the involvement of the NF-κB p65 regulation pathway in FLU action. FLU significantly suppressed the adhesion of SW480 cells and reduced the expression of adhesion markers (ICAM-1, αE-catenin; β-catenin; integrin α5 and β1). Moreover, a significant anti-migratory potential of FLU was manifested in the SW620 cells. In addition, FLU suppressed the phosphorylation of NF-κB p65 and potentiated the suppression of several metastatic markers (ICAM-1, EpCAM, integrin α5, β1, α-tubulin) caused by NF-κB p65 silencing. FLU has a significant anti-migratory effect in intestinal cancer cell SW480 and its lymph node metastatic cells SW620. FLU decreases the expression of some proteins involved in metastatic processes and inhibits activation of NF-κB p65.

High expression of class III β-tubulin in upper gastrointestinal cancer types.

Class III β-tubulin (TUBB3) is a component of microtubules of neuronal cells that is upregulated in various cancer entities. To better understand the role of TUBB3 in upper gastrointestinal tract cancer types, the present study assessed TUBB3 expression in tissue microarrays including 189 gastric and 428 esophageal cancer. TUBB3 expression was detected in 62.4% of gastric cancer, 73.8% of esophageal adenocarcinoma and 88.7% of esophageal squamous cell cancer, while control samples of normal esophageal and gastric epithelium were TUBB3-negative. TUBB3 positivity was not associated with the International Union Against Cancer classification, World Health Organization grading, lymph node involvement or distant metastasis in any entity. Of note, TUBB3 expression was associated with tumor localization and prognosis in gastric cancer, with the tumor stage in esophageal adenocarcinoma, and with the resection margin in esophageal squamous cell cancer. In conclusion, the substantial rate of positivity for TUBB3 already in early stages of gastric cancer in combination with the lack of a further increase in frequency with tumor stage, may suggest, that TUBB3 upregulation is rather relevant for cancer development than for cancer progression. TUBB3 might be a suitable prognostic biomarker in gastric cancer types.

Current and future therapies for targeting HER2 mutations in gastrointestinal cancer

ABSTRACTIntroduction: Gastrointestinal (GI) cancers altogether represent the most common cancer type. HER2 is found to be present in nearly all histologic types of GI cancers in variable degrees of expression. Over the last decade, substantial advances have been made in targeting HER2-positive cancers.Areas covered: The present review summarizes the current progress and future directions for HER2 targeted therapies in GI cancers, including esophagogastric, pancreaticobiliary, and colon cancers. To date trastuzumab is the only anti-HER2 therapy approved for metastatic esophagogastric adenocarcinoma. Efforts are ongoing to expand the therapeutic role of HER2 to other GI cancers and overcome mechanisms of drug resistance. Novel agents and combinations are being tested in most HER2 positive GI cancers including early stage disease. These are of recent interest in colorectal cancer with studies indicating that HER2 overexpression might increase resistance to anti-EGFR therapy and may be potentially targeted.Expert commentary: With the current ability to sequence tumors and detect genetic alterations, emphasis should be put on genomically-selected pan-tumor targeted therapies. HER2 is a perfect example of a promising drug target in GI cancers.

The Use of Circulating Tumor DNA for Prognosis of Gastrointestinal Cancers.

Gastrointestinal cancers, including oesophageal, gastric and colorectal cancers (CRC) have high rates of disease recurrence despite curative resection. There are a number of recent studies that have investigated the use of circulating tumor DNA (ctDNA) for prognostic value in these cancers. We reviewed studies that had been published prior to March 2018 that assessed the prognostic values of ctDNA in patients with oesophageal and gastric cancers, gastrointestinal stromal tumors (GIST) and CRC. We identified 63 eligible clinical studies that focussed on recurrence and survival. Studies assessed investigated various ctDNA biomarkers in patients with different stages of cancer undergoing surgical resection, chemotherapy and no treatment. For oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, methylation of certain genes such as APC and DAPK have been highlighted as promising biomarkers for prognostication, but these studies are limited and more comprehensive research is needed. Studies focusing on gastric cancer patients showed that methylation of ctDNA in SOX17 and APC were independently associated with poor survival. Two studies demonstrated an association between ctDNA and recurrence and survival in GIST patients, but more studies are needed for this type of gastrointestinal cancer. A large proportion of the literature was on CRC which identified both somatic mutations and DNA methylation biomarkers to determine prognosis. ctDNA biomarkers that identified somatic mutations were more effective if they were personalized based on mutations found in the primary tumor tissue, but ctDNA methylation studies identified various biomarkers that predicted increased risk of recurrence, poor disease free survival and overall survival. While the use of non-invasive ctDNA biomarkers for prognosis is promising, larger studies are needed to validate the clinical utility for optimizing treatment and surveillance strategies to reduce mortality from gastrointestinal cancers.

Maintenance use of non-steroidal anti-inflammatory drugs and risk of gastrointestinal cancer in a nationwide population-based cohort study in Sweden

ObjectivesAspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are potential candidates for chemoprevention of gastrointestinal cancer. We aimed to assess the association between contemporary NSAID use (≥180 days) and gastrointestinal cancer.DesignNationwide...

Demographic characteristics and the first program of colorectal cancer (CRC) screening in north of Iran (2016).

Colorectal cancer (CRC) is one of the most common types of gastrointestinal cancers. This study aimed to determine the demographic characteristics and their relationships with the results of the first screening program for CRC in people over 50 years old in northern Iran. This cross-sectional study was conducted in 2016 on 924 eligible people over 50 years old. Initial screening was done by IFOBT and then colonoscopy was performed if the results were positive. The demographic characteristics of individuals including age, sex, place of residence, marital status, body mass index (BMI) and education level were investigated with the results of the colonoscopy and the test results. The mean age of participants was 59.38 years, and the participation of women (57.0%) and rural residents (54.2%) were higher in the screening program. According to the demographic variables, age was considered as a strong independent predictor variable, so that the prevalence of positive test results was more than 2 times higher in subjects older than 70 compared with subjects aged ≤60 (OR =2.05; 95% CI, 1.18-3.55, P=0.010). Also, the chance of positive test result in the age group ≤55 years old was 23%, with an increase of 64% in the age group above 75 years (P<0.001). Among the positive test subjects, 118 cases underwent colonoscopy. The prevalence of IFOBT positivity was increased with age. Therefore, given the aging population of the country, it is recommended to emphasize on the screening of older people in the general population.

Identification of potential oncogenic LncRNA RP11-474D1.3 in colorectal cancer.

e15611Background: Colorectal cancer (CRC) is the most common type of gastrointestinal cancer and is the third leading cause of cancer patient’s death worldwide. Long noncoding RNAs (lncRNAs) are a ...

Clinical implementation of a comprehensive targeted amplicon sequencing system for the patients with gastrointestinal cancer as a real world evidence in Japan.

329 Background: Clinical implementation of genome sequencing is recently prevailing in the treatment for cancer. We have launched an in-house clinical sequencing system to perform exhaustive targeted exome sequencing for patients with all types of cancer, as an outpatient service. We have analyzed the clinical utility of this system for patients with gastrointestinal cancer to elucidate real world evidence. Methods: Genomic DNA was extracted from tumor tissues and peripheral blood sera of 86 patients with different types of gastrointestinal cancer, from April 2016 to April 2017. The top five types of primary cancer were colorectal (34%), pancreas (28%), stomach (13%), biliary tract (12%), and esophagus (8%). We performed a targeted amplicon exome sequencing for 160 cancer-related genes. The sequencing data was analyzed using an original bioinformatics pipeline within three days, and we identified cancer-specific somatic gene alterations such as SNV (Single Nucleotide Variation), Ins (Insertion)/Del (Deletion), and CNV (Copy Number Variation). The primary endpoints were the detection rates of potential actionable and druggable genes. The secondary endpoints were the detection rates of incidental germline variants and the period from initial visit to elucidation of the results to the patients. Results: Actionable and druggable gene alterations were detected in 97% (83/86) and 65% (56/86) of the subjects, respectively. Actionable gene alterations were frequently detected in TP53 (64/86), KRAS (38/86), APC (25/86), ARID1A (11/86), and FBXW7 (10/86). Druggable gene alterations were detected in ARID1A (11/86), and FBXW7 (10/86), BRAF (7/86), BRCA1/2 (6/86), and EGFR (4/86). Incidental germline variants were detected only in 6% (5/86) of all the patients. The median period of examination was 30 days (10-78 days). Seven out of the 86 patients (8%) were treated with therapeutic agents, based on the results of our clinical sequencing. Conclusions: Our clinical sequencing system provided a large number of cancer patients with clinically valuable genomic information available in selecting anticancer drugs within about a month.

SP1 reduces autophagic flux through activating p62 in gastric cancer cells.

Gastric cancer is the most common type of gastrointestinal cancer, causing mortality worldwide. However, the underlying molecular mechanism in gastric cancer progression remains unclear. The autophagic flux was determined in gastric cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using western blotting, reverse transcription‑polymerase chain reaction and immunofluorescence staining. Luciferase and ChIP assays were performed to detect the potential underlying mechanism of SP1 in gastric cancer cells. Lastly, immunohistochemistry was also performed on SP1 and p62 expression levels in human gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced the expression levels of p62 by directly binding to the promoter of p62. Analysis of gastric cancer specimen staining established that p62 expression levels were increased in SP1‑positve gastric tissues. The present study provided evidence for a novel mechanism regulating autophagy in gastric cancer cells.

Prognostic role of HSPs in human gastrointestinal cancer: a systematic review and meta-analysis.

BackgroundHeat shock proteins (HSPs) have been reported to be overexpressed in a wide range of human tumors. It has been shown that HSPs act as an oncogenic regulator and are involved in tumorigenesis. The clinical and prognostic significance of HSPs in gastrointestinal cancers (GICs) remains controversial. The aim of this study was to conduct a meta-analysis to assess the prognostic value of HSPs in GICs.Materials and methodsA literature search was performed in PubMed, Cochrane Library, Web of Science, and Embase databases. Data on the relationship between expression of HSPs and survival outcomes were extracted. Pooled hazard ratios (HRs) with 95% CI were calculated.ResultsThe expression of HSPs was not associated with the overall survival (OS) of GIC patients; however, it was significantly associated with worse OS for gastric cancer (GC) and colorectal cancer (CRC) patients.ConclusionCurrent evidence suggests that a high level of HSPs may not be a potential marker to predict the survival rate for every type of GICs. However, the expression of HSPs may predict a poor prognosis for GC and CRC patients.

Investigation of fusion gene expression in HCT116 cells.

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma.

A long non-coding RNA expression signature to predict survival of patients with colon adenocarcinoma.

Colon cancer is the most common type of gastrointestinal cancer and is still the leading cause of cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been proved to be superior biomarkers in cancer diagnosis and prognosis than miRNAs and protein-coding genes. In the current study, our objective was to detect novel lncRNA biomarkers by analyzing lncRNA expression profiles and clinical data in a large cohort of patients with colon patients from The Cancer Genome Atlas (TCGA). By using Cox regression analysis, we identified two lncRNAs (SNHG6 and CTD-2354A18.1) which could be independent prognostic factors for predicting clinical outcome in colon adenocarcinoma. Then a linear combination of these two lncRNA biomarkers (SNHG6 and CTD-2354A18.1), termed two-lncRNA signature, was developed in the training set as a predictor for OS in patients with colon adenocarcinoma, and validated in the testing set and the entire patient set. This two-lncRNA signature demonstrated significant prognostic performance in both the testing set and the entire patient set which classified the patients into two groups with significantly different OS. The multivariate and stratified analysis suggested that the prognostic value of the two-lncRNA signature was independent of other traditional clinical variables. Functional analysis suggested that these two lncRNA biomarkers might be mainly involved in transcription/translation-related or DNA repair-related biological processes. In summary, our results warrant further studies on these lncRNAs that will improve our understanding of the mechanisms associated with pathogenesis and progression of colon adenocarcinoma.

Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours.

Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies. Targeted agents have provided clinical benefit in many GI cancer types. Particularly, some GI tumours are considered chemoresistant and targeted therapies have offered a new therapeutic base for their management. Hence, somatostatin receptor-directed strategies, sorafenib, and imatinib have revolutioned the management of neuroendocrine tumours (NET), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumours (GIST), respectively, and are now used as first-line treatment in many patients affected by these tumours. However, these agents face problems of resistances and identification of predictive biomarkers from imaging and/or biology. We propose a comprehensive two-part review providing a panoramic approach of the successes and failures of targeted agents in GI cancers to unravel the pharmacologic opportunities and future directions for these agents in GI oncology. In this second part, we will focus on NET, HCC, and GIST, whose treatment relies primarily on targeted therapies.

Molecular subtypes in cancers of the gastrointestinal tract.

Malignancies of the gastrointestinal tract are among the most common human cancers. The distinct tissues of origin give rise to a diverse set of diseases, such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each associating with specific clinical features. Genomic and transcriptomic analyses have further defined the heterogeneity that occurs within these cancers by identifying so-called molecular subtypes. These subtypes are characterized by specific genetic aberrations and expression signatures that suggest important biological differences. Although at first sight this subdivision of organ-specific cancers might increase the complexity of classification, closer analysis suggests that the subtypes detected in the various malignancies are recurring. For example, nearly all gastrointestinal cancers appear to present with subtypes that are either characterized by a mesenchymal gene expression signatures, extensive immune infiltration or metabolic dysregulation. Additionally, in each of the gastrointestinal malignancies, a 'canonical' subtype is recognized that retains characteristic features of the epithelial tissue of origin. These common themes can enhance our collective understanding of these malignancies, and could perhaps be therapeutically exploited. In this Review, the identification of subtypes in the various gastrointestinal cancer types are discussed along with how they could be incorporated into clinical practice.

The expression of histone deacetylase HDAC1 correlates with the progression and prognosis of gastrointestinal malignancy.

Gastrointestinal malignancy is a severe public health threat worldwide, and survival for most types of gastrointestinal cancer is very poor. Therefore, finding better cancer biomarkers to diagnose gastrointestinal malignancy and predict patient survival is essential. HDAC1 has been reported to be closely associated with several types of cancer, but the precise role of HDAC1 in gastrointestinal cancer is not clear. Recently, quite a few studies have investigated the correlation between HDAC1 expression and clinical features or prognosis in multiple types of gastrointestinal malignancies, but the results were inconsistent. In this study, we systematically reviewed the association between HDAC1 and gastrointestinal malignancy using meta-analysis methods, and 28 eligible studies were analyzed. We found that the expression level of HDAC1 in gastrointestinal malignancies, especially in colorectal cancer (OR = 10.84, 95% CI = 5.33–22.07, P< 0.00001), was higher than that in noncancerous tissue, and HDAC1 expression was closely associated with some clinical features of gastrointestinal cancer patients, such as tumor stage (OR = 1.62, 95% CI = 1.28–2.05, P < 0.0001) and tumor grade (OR = 1.75, 95% CI = 1.03–2.95, P = 0.04). In addition, we also found that patients with low HDAC1 expression showed better overall survival than those with high HDAC1 expression in gastrointestinal malignancy, especially in gastric cancer (HR = 1.88, 95% CI = 1.14–3.12, P = 0.01). Our results strongly suggest that HDAC1 may serve as a good diagnostic and prognostic marker for gastrointestinal malignancy.