Progression Of Gastrointestinal Cancers Research Articles

Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers.

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

Genetic susceptibility to Helicobacter pylori and the progression of gastrointestinal cancer

The Helicobacter pylori bacteria are spiral-shaped and grow in the stomach's mucus. During its life cycle, H. pylori produces an enzyme called urease that converts urea into ammonia. This enzyme allows the organism to survive a severe, acidic environment by converting urea into ammonia. Molecular genetic studies have identified polymorphisms functional as biomarkers of hereditary predisposition to stomach cancer. Several genes involved in inflammation have been linked to stomach cancer development. Recently, these genes' potential pathogenic and carcinogenic effects have been investigated (APC, CDH1, IL-1, BAX, NOS2, KRAS and MSH2). All these genes' processes have been researched to understand better their potential as biomarkers of gastric carcinogenesis. An in-depth analysis will be required to determine the genetic characteristics of stomach cancer related to H. pylori. It is imperative to research a variety of ethnicities to further use this influence as a critical and fundamental risk factor for stomach illness.

M6A methylation modification and immune cell infiltration: implications for targeting the catalytic subunit m6A-METTL complex in gastrointestinal cancer immunotherapy.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world's most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

Microbial gene expression analysis of healthy and cancerous esophagus uncovers bacterial biomarkers of clinical outcomes

Local microbiome shifts are implicated in the development and progression of gastrointestinal cancers, and in particular, esophageal carcinoma (ESCA), which is among the most aggressive malignancies. Short-read RNA sequencing (RNAseq) is currently the leading technology to study gene expression changes in cancer. However, using RNAseq to study microbial gene expression is challenging. Here, we establish a new tool to efficiently detect viral and bacterial expression in human tissues through RNAseq. This approach employs a neural network to predict reads of likely microbial origin, which are targeted for assembly into longer contigs, improving identification of microbial species and genes. This approach is applied to perform a systematic comparison of bacterial expression in ESCA and healthy esophagi. We uncover bacterial genera that are over or underabundant in ESCA vs healthy esophagi both before and after correction for possible covariates, including patient metadata. However, we find that bacterial taxonomies are not significantly associated with clinical outcomes. Strikingly, in contrast, dozens of microbial proteins were significantly associated with poor patient outcomes and in particular, proteins that perform mitochondrial functions and iron-sulfur coordination. We further demonstrate associations between these microbial proteins and dysregulated host pathways in ESCA patients. Overall, these results suggest possible influences of bacteria on the development of ESCA and uncover new prognostic biomarkers based on microbial genes. In addition, this study provides a framework for the analysis of other human malignancies whose development may be driven by pathogens.

Natriuretic Peptides in Gastrointestinal Cancer: Biomarkers and Potential Therapeutic Targets.

Gastrointestinal (GI) cancers are an important health problem globally. Natriuretic peptides are hormones that have a crucial role in human physiology. There are a variety of treatments for GI cancer, but conventional therapies have side effects and low efficacy. Studies have demonstrated that natriuretic peptides are therapeutic in different cancer types. Natriuretic peptides are best known for their involvement in regulating blood pressure and blood volume. The anti-tumor effect exerted by natriuretic peptides is via their inhibitory effects on DNA synthesis and by their effects on apoptosis. The anti-proliferative role of natriuretic peptides has been shown in human breast cancer, prostate, colon, pancreatic, lung, ovarian, and other tumors. The roles of natriuretic peptides in these cancers are diverse and not well understood. Therefore, we have reviewed the recent literature on natriuretic peptides in GI cancers as a common malignancy in adults to assess the pathways that NPs are involved in the progression of GI cancers and its effect on the prevention or treatment of GI cancers.

The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review.

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N6-methyladenosine (m6A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m6A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m6A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m6A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m6A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets.

MiR-3133 inhibits gastrointestinal cancer progression through activation of Hippo and p53 signalling pathways via multi-targets.

Malignant cell growth and chemoresistance, the main obstacles in treating gastrointestinal cancer (GIC), rely on the Hippo and p53 signalling pathways. However, the upstream regulatory mechanisms of these pathways remain complex and poorly understood. Immunohistochemistry (IHC), western blot and RT-qPCR were used to analyse the expression of RNF146, miR-3133 and key components of Hippo and p53 pathway. CCK-8, colony formation, drug sensitivity assays and murine xenograft models were used to investigate the effect of RNF146 and miR-3133 in GIC. Further exploration of the upstream regulatory mechanism was performed using bioinformatics analysis, dual-luciferase reporter gene, immunoprecipitation assays and bisulfite sequencing PCR (BSP). Clinical samples, in vitro and in vivo experiments demonstrated that RNF146 exerts oncogenic effects in GIC by regulating the Hippo pathway. Bioinformatics analysis identified a novel miRNA, miR-3133, as an upstream regulatory factor of RNF146. fluorescence in situ hybridization and RT-qPCR assays revealed that miR-3133 was less expressed in gastrointestinal tumour tissues and was associated with adverse pathological features. Functional assays and animal models showed that miR-3133 promoted the proliferation and chemotherapy sensitivity of GIC cells. miR-3133 affected YAP1 protein expression by targeting RNF146, AGK and CUL4A, thus activating the Hippo pathway. miR-3133 inhibited p53 protein degradation and extended p53's half-life by targeting USP15, SPIN1. BSP experiments confirmed that miR-3133 promoter methylation is an important reason for its low expression. miR-3133 inhibits GIC progression by activating the Hippo and p53 signalling pathways via multi-targets, including RNF146, thereby providing prognostic factors and valuable potential therapeutic targets for GIC.

MK2 drives progression of pancreas and colon cancers by suppressing CD8+ T cell cytotoxic function and is a potential immunotherapy target.

Immune cell composition is a critical and dynamic component of the tumor microenvironment, which has an impact on immunosuppression and progression of cancer. T cells, especially CD8+ T cells, are one of the major immune cell types responsible for tumor cell killing employing receptor-ligand mediated apoptosis and/or releasing lytic granules among others. Accumulating evidence highlighted that adoptive transfer of activated and/or modified immune cells can enhance anti-tumorigenic immune responses and serve as promising therapy approach for patients with cancers. The mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a serine/threonine protein kinase, which controls production and secretion of numerous pro-inflammatory cytokines and chemokines involved in tumorigenesis. However, limited efforts have been made to learn how MK2 may affects CD8+ T cell action and function in the tumor microenvironment especially in gastrointestinal cancers. To explore the therapeutic potential of MK2 in the immune response mediated by CD8+ T cells, RAG1 knockout mice with PK5L1940 and BRAF cells-derived allograft tumors were treated with WT or MK2 knockout CD8+ T cells. The phenotype of CD8+ T cells with MK2 depletion were evaluated in vitro. Immunofluorescence staining, real-time PCR and multiplex analysis were utilized to estimate the expression of apoptotic and lytic factors. Here, we show that CD8+ T cells with MK2 depletion prevent gastrointestinal cancer growth, which is accompanied by enhanced expression and secretion of factors related to apoptosis. Moreover, using in vitro and in vivo approaches, we found that depletion of MK2 lead to hyperactivation of CD8+ T cells and enhanced anti-tumor immunity. Overall, we documented that MK2 drives the progression of gastrointestinal cancers and prevents immune response generated by CD8+ T cells suggesting potential implications of MK2 in the immunotherapy of gastrointestinal cancers.

New insights on the interplays between m6A modifications and microRNA or lncRNA in gastrointestinal cancers.

N6-Methyladenosine (m6A) methylation is one of the most extremely examined RNA modifications. M6A modification evidently impacts cancer development by effecting RNA metabolism. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in multiple essential biological processes by regulating gene expression at the transcriptional and post-transcriptional levels. Accumulated evidences indicated that m6A is involved in regulating the cleavage, stability, structure, transcription, and transport of lncRNAs or miRNAs. Additionally, ncRNAs also play significant roles in modulating m6A levels of malignant cells by participating in the regulation of m6A methyltransferases, the m6A demethylases and the m6A binding proteins. In this review, we systematically summarize the new insight on the interactions between m6A and lncRNAs or miRNAs, as well as their impacts on gastrointestinal cancer progression. Although there are still extensive studies on genome-wide screening of crucial lncRNAs or miRNAs involved in regulating m6A levels of mRNAs and disclosing differences on mechanisms of regulating m6A modification of lncRNAs, miRNAs or mRNAs in cancer cells, we believe that targeting m6A-related lncRNAs and miRNAs may provide novel options for gastrointestinal cancer treatments.

Exploring the Correlation Between GPR176, a Potential Target Gene of Gastric Cancer, and Immune Cell Infiltration.

GPR176, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how GPR176 affects tumor immunity and patient prognosis in gastric cancer (GC). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of GPR176 in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between GPR176 and clinical traits. Additionally, the potential correlation between GPR176, immune checkpoint genes, and immune cell infiltration levels was investigated. As per the research findings, GC tissues had higher levels of GPR176 than normal tissues. Additionally, individuals with high expression of GPR176 had a worse 10-year overall survival (OS), in contrast with those having a low expression of GPR176 (p < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of GPR176 demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of GPR176, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of GPR176 expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment. By examining GPR176 from various biological perspectives, it was determined that GPR176 can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that GPR176 is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.

Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective.

Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.

Role of exosomal ncRNAs released by M2 macrophages in tumor progression of gastrointestinal cancers.

Macrophages (MΦs) type 2 (M2) play crucial roles in the pathogenesis of gastrointestinal cancers (GIC) by enhancing tumor progression, invasion, and metastasis. Polarized M2 has been linked to the increase of GIC tumorigenesis anddrug resistance. Several studies reported that M2-derived exosomal non-coding RNAs (Exos-ncRNAs) play pivotal roles in the modulation of the GIC tumor microenvironment (TME) and mostly promote drug resistance and immunosuppression. The impact of M2-Exos-ncRNAs is attributed to altered signaling pathways, enhancement of immunoregulatory mechanisms, and post-transcriptional modulation. Recent studies described novel targets in M2-TAMs-derived Exos-ncRNAs and potential promising clinical outcomes such as inhibiting tumorformation, invasion, and metastasis. Highlighting current knowledge of M2-Exos-ncRNAs involved in GIC pathogenesis and immunomodulation would thus be a significant contribution to improving clinical outcomes. In this review, we summarize recent updates on the role of M2-TAMs-Exos-ncRNAs in GIC pathogenesis, immunosuppression, and drug resistance. A deep understanding of M2-TAMs-derived Exos-ncRNAs could help to identify potential biomarkers and therapeutic targets.

Exosomal LncRNAs in Gastrointestinal Cancer: Biological Functions and Emerging Clinical Applications.

Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated.

Nanotechnology and machine learning enable circulating tumor cells as a reliable biomarker for radiotherapy responses of gastrointestinal cancer patients

A highly sensitive, circulating tumor cell (CTC)-based liquid biopsy was used to monitor gastrointestinal cancer patients during treatment to determine if CTC abundance was predictive of disease recurrence. The approach used a combination of biomimetic cell rolling on recombinant E-selectin and dendrimer-mediated multivalent immunocapture at the nanoscale to purify CTCs from peripheral blood mononuclear cells. Due to the exceptionally high numbers of CTCs captured, a machine learning algorithm approach was developed to efficiently and reliably quantify abundance of immunocytochemically-labeled cells. A convolutional neural network and logistic regression model achieved 82.9% true-positive identification of CTCs with a false positive rate below 0.1% on a validation set. The approach was then used to quantify CTC abundance in peripheral blood samples from 27 subjects before, during, and following treatments. Samples drawn from the patients either prior to receiving radiotherapy or early in chemotherapy had a median 50 CTC ml−1 whole blood (range 0.6–541.6). We found that the CTC counts drawn 3 months post treatment were predictive of disease progression (p = .045). This approach to quantifying CTC abundance may be a clinically impactful in the timely determination of gastrointestinal cancer progression or response to treatment.

Exosomes as drug delivery system in gastrointestinal cancer.

Gastrointestinal cancer is one of the most common malignancies with relatively high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived from most cells and widely distributed in body fluids. They are natural endogenous nanocarriers with low immunogenicity, high biocompatibility, and natural targeting, and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins, lipids, and other bioactive components, which can play a role in information transmission and regulation of cellular physiological and pathological processes during the progression of gastrointestinal cancer. In this paper, the role of exosomes in gastrointestinal cancers is briefly reviewed, with emphasis on the application of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the challenges faced by exosome-based drug delivery systems are discussed.

The evaluation of HERV-K np9, rec, gag expression in isolated human peripheral blood mononuclear cell (PBMC) of gastric and colon cancer

Background: In the current age of diagnostic approaches in cancer, countless efforts have been allocated to identify novel and efficient biomarkers to detect cancer in its early stages. We focused on evaluating the correlation between the progression of gastrointestinal cancer, a leading cause of cancer death worldwide, and human endogenous retrovirus (HERV).Materials and Methods: In this study, we conducted a study on the peripheral blood mononuclear cells (PBMC) gathered from gastric and colon cancer patients. We focused on HERV-K rec, np9, gag expression analysis by quantitative real-time PCR, after extraction of RNA and synthesizing cDNA.Results: Unlike np9 whose expression increased significantly in the colon and gastric cancers, the mRNA level of the rec gene declined in both cancers. Moreover, our data illustrated that the over-expression of the gag gene was only observed in colon cancerous cells rather than gastric malignancy.Conclusions: Overall, given the correlation between the expression level of HERV-associated genes and gastrointestinal cancer, our study suggests that these genes could be considered beneficial markers for cancer diagnosis. However, researchers should conduct studies in future articles on whether these genes can be employed as biomarkers in gastrointestinal cancer.

In vitro and Pharmacoinformatics-based phytochemical screening for anticancer impacts of pistachio hull essential oil on AGS, PLC/PRF/5, and CACO2 cell lines.

The essential oil of pistacia vera (cv. Ohadi) hull (PHEO) was checked using gas chromatography mass spectrometry (GC/MS) analysis. It was studied the genes of the wnt pathway with a certain concentration of PHEO on Human gastric cancer (AGS), human hepatocellular carcinoma (PLC/PRF/5), and human colon cancer (CACO2) cell lines. After evaluating the survival rate of cancer cells by MTT test and determining IC50, pistachio hull essential oil (PHEO) was used for 24-hours to treat the cells. After RNA extraction, the expression of wnt pathway genes was evaluated by Real-Time PCR. Considering the crucial role of β-catenin accumulation and its effect on the progression of gastrointestinal cancers, Western blot analysis was also used to determine the effect of PHEO in protein expression of β-catenin inhibition. Also, an in silico analysis was carried out to investigate the effect of PHEO extracted compounds on protein expression of β-catenin and FZD7 inhibition. According to the results, wnt pathway genes were changed in samples treated using PHEO. The results showed the up-regulation of GSK-3β and down-regulation of Wnt-1, LEF-1, TCF1, and CTNNB1 genes compared to the control. We showed inhibition of β-catenin protein in cancer cell lines. Four compounds of PHEO were suggested to have an inhibition effect on β-catenin and FZD7. These compounds can be useful in the treatment of gastrointestinal cancers. Altogether, the inhibitory role of β-catenin protein can be very effective and can be considered one of the therapeutic goals in the treatment of gastrointestinal cancers.

Pleiotropic effects of DCLK1 in cancer and cancer stem cells.

Doublecortin-like kinase 1 (DCLK1), a protein molecule, has been identified as a tumor stem cell marker in the cancer cells of gastrointestinal, pancreas, and human colon. DCLK1 expression in cancers, such as breast carcinoma, lung carcinoma, hepatic cell carcinoma, tuft cells, and human cholangiocarcinoma, has shown a way to target the DCLK1 gene and downregulate its expression. Several studies have discussed the inhibition of tumor cell proliferation along with neoplastic cell arrest when the DCLK1 gene, which is expressed in both cancer and normal cells, was targeted successfully. In addition, previous studies have shown that DCLK1 plays a vital role in various cancer metastases. The correlation of DCLK1 with numerous stem cell receptors, signaling pathways, and genes suggests its direct or an indirect role in promoting tumorigenesis. Moreover, the impact of DCLK1 was found to be related to the functioning of an oncogene. The downregulation of DCLK1 expression by using targeted strategies, such as embracing the use of siRNA, miRNA, CRISPR/Cas9 technology, nanomolecules, specific monoclonal antibodies, and silencing the pathways regulated by DCLK1, has shown promising results in both in vitro and in vivo studies on gastrointestinal (GI) cancers. In this review, we will discuss about the present understanding of DCLK1 and its role in the progression of GI cancer and metastasis.

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities.

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.

Molecular Regulatory Roles of Long Non-coding RNA HOTTIP: An Overview in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and are highly characterised by poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as potential novel molecular targets for combating cancer, as they are highly associated with carcinogenesis and have a great impact on cancer progression. Amongst lncRNAs, HOTTIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impact cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity, and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. Overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.