Development Of Colorectal Cancer Research Articles

Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.

Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis. Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC. Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk. This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.

Targeting CREB-binding protein (CBP) abrogates colorectal cancer stemness through epigenetic regulation of C-MYC.

Colorectal cancer (CRC) is a common cancer worldwide with an increasing annual incidence. Cancer stem cells (CSCs) play important roles in the occurrence, development, recurrence, and metastasis of CRC. The molecular mechanism regulating the development of colorectal CSCs remains unclear. The discovery of human induced pluripotent stem cells (hiPSCs) through somatic cell reprogramming has revolutionized the fields of stem cell biology and translational medicine. In the present study, we converted hiPSCs into cancer stem-like cells by culture with conditioned medium (CM) from CRC cells. These transformed cells, termed hiPSC-CSCs, displayed cancer stem-like properties, including a spheroid morphology and the expression of both pluripotency and CSC markers. HiPSC-CSCs showed tumorigenic and metastatic abilities in mouse models. The epithelial-mesenchymal transition phenotype was observed in hiPSC-CSCs, which promoted their migration and angiogenesis. Interestingly, upregulation of C-MYC was observed during the differentiation of hiPSC-CSCs. Mechanistically, CREB binding protein (CBP) bound to the C-MYC promoter, while histone deacetylase 1 and 3 (HDAC1/3) dissociated from the promoter, ultimately leading to an increase in histone acetylation and C-MYC transcriptional activation during the differentiation of hiPSC-CSCs. Pharmacological treatment with a CBP inhibitor or abrogation of CBP expression with a CRISPR/Cas9-based strategy reduced the stemness of hiPSC-CSCs. This study demonstrates for the first time that colorectal CSCs can be generated from hiPSCs. The upregulation of C-MYC via histone acetylation plays a crucial role during the conversion process. Inhibition of CBP is a potential strategy for attenuating the stemness of colorectal CSCs.

Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts.

Colorectal cancer (CRC) is still a leading cause of cancer deaths worldwide. Thus, identifying the aberrant genes and proteins underlying disease pathogenesis is critical to improve early detection methods and develop novel therapeutic strategies. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a predominant form of genome instability. It is a driver of genetic heterogeneity found in ~85% of CRCs. Although CIN contributes to CRC pathogenesis, the molecular determinants underlying CIN remain poorly understood. Recently, EMI1, an F-box protein, was identified as a candidate CIN gene. In this study, we sought to determine the impact reduced EMI1 expression has on CIN and cellular transformation. Coupling siRNA-based silencing and CRISPR/Cas9 knockout clones with quantitative imaging microscopy we evaluated the impact reduced EMI1 expression has on CIN and cellular transformation in four colonic epithelial cell contexts. Quantitative imaging microscopy data revealed that reduced EMI1 expression induces increases in CIN phenotypes in both transient (siRNA) and constitutive (CRISPR/Cas9) cell models that are associated with increases in DNA damage and cellular transformation phenotypes in long-term studies. This study determined that reduced EMI1 expression induces CIN and promotes cellular transformation, which is consistent with a role in early CRC development.

MiR-4486 inhibits colorectal cancer proliferation via targeting MAP2K4 to inhibit the activation of the p38MAPK/JNK signaling

ObjectiveSince MAP2K4 was reportedly involved in colorectal cancer development and the p38MAPK/JNK signaling transcription, this study aimed to investigate the mechanism by which the microRNA (miR)-4486 acts on colorectal cell proliferation. MethodsRT-PCR was conducted to measure the expression levels of the MAP2K4 and miR-4486 in NCM460, SW1116, and HCT116 cells. TargetScanHuman site anticipated that MAP2K4 may be a target of miR-4486. The dual-luciferase reporter assay confirmed their relationship. After plasmids of miR-4486 mimic and si-MAP2K4 transfection, MAP2K4 was quantified again, The CCK-8 assay was carried out to assess cell proliferation, while Scratch and Transwell assays were used to evaluate cell migration and invasion. Finally, miR-4486 mimic and SB203580 were applied in HCT116 and SW1116 cells separately or in combination. CCK-8, Scratch and Transwell assay were performed again. In addition, the proteins including c-capase3, Bax, Bcl2, MAP2K4, and the p38MAPK/JNK signaling-related proteins expression levels were quantified by Western blot (WB). ResultsCompared with the NCM460 cells, the expression level of MAP2K4 was elevated, while the expression level of miR-4486 was reduced in SW1116 and HCT116 cells. The results showed that elevated levels of miR-4486 suppressed cell proliferation, migration, and invasion in colorectal cells by downregulating MAP2K4 expression. miR-4486 mimic showed similar effects to SB203580, which promoted colorectal cell apoptosis and inhibited the p38 MAPK/JNK signaling transcription. ConclusionmiR-4486 may target MAP2K4 to inhibit colorectal cell proliferation by inhibiting the activation of the p38/JNK signaling pathway.

Long non‑coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (Review).

Colorectal cancer (CRC) ranks as the 3rd most common cancer globally and is the 2nd leading cause of cancer-related death. Owing to the lack of specific early symptoms and the limitations of existing early diagnostic methods, most patients with CRC are diagnosed at advanced stages. To overcome these challenges, researchers have increasingly focused on molecular biomarkers, with particular interest in long non-coding RNAs (lncRNAs). These non-protein-coding RNAs, which exceed 200 nucleotides in length, play critical roles in the development and progression of CRC. The stability and detectability of lncRNAs in the circulatory system make them promising candidate biomarkers. The analysis of circulating lncRNAs in peripheral blood represents a potential option for minimally invasive diagnostic tests based on liquid biopsy samples. The present review aimed to evaluate the efficacy of lncRNAs with altered expression levels in peripheral blood as diagnostic markers for CRC. Additionally, the clinical significance of lncRNAs as prognostic markers for this disease were summarized.

Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM’s Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.

Phytochemicals and colorectal cancer: About polyphenols

Dietary consumption of polyphenols, found in fruits and vegetables, has been associated with a potentially protective role in colorectal cancer (CRC). To establish the state of knowledge regarding advances in polyphenols, CCR and action mechanisms a systematic review and an analysis of information available until 2021 were made. Results indicate that only some polyphenols have in vitro, preclinical and clinical studies. These studies showed that polyphenols will inhibit human CRC cell invasion, migration, metastasis formation, tumor growth. Action mechanisms involve signaling pathways that modulate genes, proteins, markers or cell death inductors, like the AMPK pathway, caspases, Bcl-2, p-Akt, and NF-kB, lysosomal and mitochondrial dysfunction, cellular cycle arrest, among the best known and implied in CRC. Overall, in vitro, preclinical and clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive or therapeutic impacts of dietary phytochemicals on CRC development deserve further research.

USP36 promotes colorectal cancer progression through inhibition of p53 signaling pathway via stabilizing RBM28.

Colorectal cancer (CRC) stands as the second most common cause of cancer-related mortality globally and p53, a widely recognized tumor suppressor, contributes to the development of CRC. Ubiquitin-specific protease 36 (USP36), belonging to the deubiquitinating enzyme family, is involved in tumor progression across multiple cancers. However, the underlying molecular mechanism in which USP36 regulates p53 signaling pathway in CRC is unclear. Here, our study revealed that USP36 was increased in CRC tissues and associated with unfavorable prognosis. Functionally, elevated USP36 could promote proliferation, migration, and invasion of CRC cells in vitro and in vivo. Mechanistically, USP36 could interact with and stabilize RBM28 via deubiquitination at K162 residue. Further, upregulated RBM28 could bind with p53 to suppress its transcriptional activity and therefore inactivate p53 signaling pathway. Collectively, our investigation identified the novel USP36/RBM28/p53 axis and its involvement in promoting cell proliferation and metastasis in CRC, which presents a promising therapeutic strategy for CRC treatment.

Inhibition of the NF-κB/HIF-1α signaling pathway in colorectal cancer by tyrosol: a gut microbiota-derived metabolite

BackgroundThe development and progression of colorectal cancer (CRC) are influenced by the gut environment, much of which is modulated by microbial-derived metabolites. Although some research has been conducted on the...

Functional links between the microbiome and the molecular pathways of colorectal carcinogenesis.

Colorectal cancer (CRC) is a common cancer, with a concerning rise in early-onset CRC cases, signalling a shift in disease epidemiology. Whilst our understanding of the molecular underpinnings of CRC has expanded, the complexities underlying its initiation remain elusive, with emerging evidence implicating the microbiome in CRC pathogenesis. This review synthesizes current knowledge on the intricate interplay between the microbiome, tumour microenvironment (TME), and molecular pathways driving CRC carcinogenesis. Recent studies have reported how the microbiome may modulate the TME and tumour immune responses, consequently influencing cancer progression, and whilst specific bacteria have been linked with CRC, the underlying mechanisms remains poorly understood. By elucidating the functional links between microbial landscapes and carcinogenesis pathways, this review offers insights into how bacteria orchestrate diverse pathways of CRC development, shedding light on potential therapeutic targets and personalized intervention strategies.

Gut commensal Alistipes as a potential pathogenic factor in colorectal cancer

Although previous research has shown that inflammation is associated with development of colorectal cancer (CRC), questions remain about whether inflammatory factor-secreting bacteria play a crucial role in CRC development. The potential role of gut microbiota in secreting inflammatory factors involved in the carcinogenesis of CRC among Chinese patients was explored in this study. 16S rRNA sequencing was utilized to evaluate the distinct microbial characteristics between patients with CRC and colorectal adenoma. The serum levels of TNF-α, IL-6 and IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA), while the expression of LRG1 and TGF-β1 in tissues was evaluated by immunohistochemistry. The correlation between gut microbiota and inflammatory factor signaling was analyzed. Compared with the adenoma group, CRC patients exhibit distinct pathologies. Moreover, elevated levels of CEA, erythrocytes and haemoglobin in the blood of CRC patients were found. In addition, CRC patients have significantly higher levels of TNF-α, IL-6, IL-10, LRG1 and TGF-β1. Spearman correlation analysis revealed that LRG1 was positively related to IL-6 and TNF-α, respectively. The correlation analysis results of TGF-β1 were consistent with the above. The abundance of Blautia and Streptococcus was lower in CRC patients, while the relative abundance of Alistipes, Peptostreptococcus and Porphyromonas was significantly elevated. Moreover, positive correlations between Alistipes and inflammatory factor signaling were also found. Our results suggest that gut commensal Alistipes is a key bacterium with pro-inflammatory properties in the CRC carcinogenesis. TNF-α and IL-6 associated with Alistipes might activate LRG1/TGF-β1 signaling which contributed to the carcinogenesis of CRC.

Effect of smoking on the risk of gastrointestinal cancer after cholecystectomy: A national population-based cohort study.

The role of smoking in the incidence of colorectal cancer (CRC) or gastric cancer (GC) in populations undergoing cholecystectomy has not been investigated. To evaluate the effect of smoking on CRC or GC development in cholecystectomy patients. A total of 174874 patients who underwent cholecystectomy between January 1, 2010 and December 31, 2017 were identified using the Korean National Health Insurance Service claims database. These patients were matched 1:1 with members of a healthy population according to age and sex. CRC or GC risk after cholecystectomy and the association between smoking and CRC or GC risk in cholecystectomy patients were evaluated using adjusted hazard ratios (HRs) and 95%CIs. The risks of CRC (adjusted HR: 1.15; 95%CI: 1.06-1.25; P = 0.0013) and GC (adjusted HR: 1.11; 95%CI: 1.01-1.22; P = 0.0027) were significantly higher in cholecystectomy patients. In the population who underwent cholecystectomy, both CRC and GC risk were higher in those who had smoked compared to those who had never smoked. For both cancers, the risk tended to increase in the order of non-smokers, ex-smokers, and current smokers. In addition, a positive correlation was observed between the amount of smoking and the risks of both CRC and GC. Careful follow-up and screening should be performed, focusing on the increased risk of gastrointestinal cancer in the cholecystectomy group, particularly considering the individual smoking habits.

Glioblastoma Arising in Lynch-like Syndrome after Repeated Development of Colorectal Cancers: A Case Report.

We herein report a patient with Lynch-like syndrome in whom a brain tumor (glioblastoma) developed after repeated resection of colorectal cancer. The patient had a significant family history of cancer. Immunohistochemical expression of mismatch repair proteins was decreased in both brain and colon tumors, but no pathogenic variant of the related genes was detected. Although brain tumors occasionally develop in Lynch syndrome, they have not been reported in cases of Lynch-like syndrome. This first report of Lynch-like syndrome with the development of glioblastoma suggests the need for further investigation on the surveillance of brain tumors in patients with this syndrome.

Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer.

Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients.

Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer.

This study investigates the dual role of ALKBH5, an eraser enzyme, in colorectal cancer (CRC), focusing on how N6-methyladenosine (m6A) mutations influence CRC development and progression. We reviewed various studies that highlighted the role of ALKBH5 in colorectal cancer (CRC). This includes the impact of ALKBH5 on tumor cell behavior including immune system interactions, invasion, and proliferation in CRC. We also looked into how ALKBH5 acts as a tumor suppressor under different conditions analyzed clinical data to assess the impact of ALKBH5 expression on outcomes in colorectal cancer patients. In CRC, ALKBH5 plays a dual role. In certain situations, it inhibits the progression of the tumor, but in other circumstances, it promotes tumor growth and immunosuppression. The interaction with RABA5 plays a role in the development of CRC. Having elevated levels of ALKBH5 has been associated with unfavorable patient outcomes, such as reduced survival rates and more advanced cancer stages. Various factors, including tumor differentiation, TNM stages, and carcinoembryonic antigen (CEA) levels, be linked to ALKBH5 expression. ALKBH5 plays a complicated and situation-specific role in colorectal cancer (CRC). Targeting ALKBH5 could result in novel therapy options that balance its tumor-promoting and tumor-fighting properties in CRC. Further research into m6A alterations and ALKBH5 could enhance CRC treatment approaches and patient outcomes.

Reactivation of SOX17 Program as Immune-Evasion Mechanism in Early Colorectal Cancer Development.

Reactivation of SOX17 Program as Immune-Evasion Mechanism in Early Colorectal Cancer Development.

STAT3 and the STAT3‑regulated inhibitor of apoptosis protein survivin as potential therapeutic targets in colorectal cancer (Review).

Colorectal cancer (CRC) is one of the leading types of cancer worldwide. CRC development has been associated with the constitutive activation of signal transducer and activator of transcription 3 (STAT3). STAT3 is a master regulator of inflammation during cancer-associated colitis, and becomes upregulated in CRC. In CRC, STAT3 is activated by IL-6, among other pro-inflammatory cytokines, inducing the expression of target genes that stimulate proliferation, angiogenesis and the inhibition of apoptosis. One of the main STAT3-regulated inhibitors of apoptosis is survivin, which is a bifunctional protein that regulates apoptosis and participates in cell mitosis. Survivin expression is normally limited to foetal tissue; however, survivin is also upregulated in tumours. In silico and experimental analyses have shown that the STAT3 interactome is relevant during CRC progression, and the constitutive STAT3-survivin axis participates in development of the tumour microenvironment and response to therapy. The presence of a STAT3-survivin axis has been documented in CRC cohorts, and the expression of these molecules is associated with poor prognosis and a higher mortality rate in patients with CRC. Thus, STAT3, survivin, and the upstream activators IL-6 and IL-6 receptor, are considered therapeutic targets for CRC. Efforts to develop drugs targeting the STAT3-survivin axis include the evaluation of phytochemical compounds, small molecules and monoclonal antibodies. In the present review, the expression, function and participation of the STAT3-survivin axis in the progression of CRC were investigated. In addition, an update on the pre-clinical and clinical trials evaluating potential treatments targeting the STAT3-survivin axis is presented.

An Update on Blastocystis: Possible Mechanisms of Blastocystis-Mediated Colorectal Cancer.

Blastocystis is an anaerobic parasite that colonizes the intestinal tract of humans and animals. When it was first discovered, Blastocystis was considered to be a normal flora with beneficial effects on human health, such as maintaining gut hemostasis and improving intestinal barrier integrity. Later, with increasing research on Blastocystis, reports showed that Blastocystis sp. is associated with gastrointestinal disorders, colorectal cancer (CRC), and neurological disorders. The association between Blastocystis sp. and CRC has been confirmed in several countries. Blastocystis sp. can mediate CRC via similar mechanisms to CRC-associated bacteria, including infection-mediated inflammation, increased oxidative stress, induced gut dysbiosis, and damage to intestinal integrity, leading to a leaky gut. IL-8 is the main inflammatory cytokine released from epithelial cells and can promote CRC development. The causal association of Blastocystis sp. with other diseases needs further investigation. In this review, we have provided an update on Blastocystis sp. and summarized the debate about the beneficial and harmful effects of this parasite. We have also highlighted the possible mechanisms of Blastocystis-mediated CRC.

Bioengineered Anthocyanin-Enriched Tomatoes: A Novel Approach to Colorectal Cancer Prevention.

Colorectal cancer (CRC) remains a significant global health challenge, with barriers to effective prevention and treatment including tumor recurrence, chemoresistance, and limited overall survival rates. Anthocyanins, known for their strong anti-cancer properties, have shown promise in preventing and suppressing various cancers, including CRC. However, natural sources of anthocyanins often fail to provide sufficient quantities needed for therapeutic effects. Bioengineered crops, particularly anthocyanin-enriched tomatoes, offer a viable solution to enhance anthocyanin content. Given its large-scale production and consumption, tomatoes present an ideal target for bioengineering efforts aimed at increasing dietary anthocyanin intake. This review provides an overview of anthocyanins and their health benefits, elucidating the mechanisms by which anthocyanins modulate the transcription factors involved in CRC development. It also examines case studies demonstrating the successful bioengineering of tomatoes to boost anthocyanin levels. Furthermore, the review discusses the effects of anthocyanin extracts from bioengineered tomatoes on CRC prevention, highlighting their role in altering metabolic pathways and reducing tumor-related inflammation. Finally, this review addresses the challenges associated with bioengineering tomatoes and proposes future research directions to optimize anthocyanin enrichment in tomatoes.

Abstract C110: The role of the S100 family signaling pathway proteins in Hispanic colorectal cancer disparities

Abstract Colorectal cancer (CRC) is a global health concern, ranking as the second deadliest and third most diagnosed cancer. In the United States alone, it is estimated that there will be 152,810 new cases of CRC in 2024. CRC has an overall survival rate of 90% when detected in its early stages (Stage I/II). However, due to low screening rates, only 39% of CRC patients in the U.S. are diagnosed during the early stage, particularly among the minority groups like Hispanics. This disparity can be attributed to various factors, including limited access to health care facilities and socio-economic barriers. Among Hispanics, CRC diagnosis and screening rate are lower, resulting in a higher incidence of late-stage (Stage III/IV) diagnosis compared to Non-Hispanic Whites (NHW). Only 33% of Hispanics receive timely diagnosis, and merely 49% undergo recommended screening protocols, in comparison to a diagnosis rate of 35% and screening rate of 58% in NHW. Addressing this health disparity emphasizes the urgent need for targeted interventions to improve early screening and diagnosis within the Hispanic population. We hypothesize that genetic factors across different ethnicities/races may influence gene expression patterns during various stages, thereby contributing to CRC tumorigenesis and progression. To enhance the chances of identifying markers for early detection and diagnosis among Hispanics, we aim to identify new ethnicity-specific transcriptomic profiles. RNA sequencing of Hispanic CRC, NHW CRC and their respective normal tissues adjacent to the tumor (NAT), revealed unique sets of differentially expressed genes (DEGs) with a log2 foldchange of ≥ 2.0 and ≤ -2.0 and p-adjusted value ≤ 0.05 in Hispanic (1831) and NHW (1225) CRC populations compared to their respective NATs. Further analysis identified DEGs specific to early (1012) and late (765) stages of CRC within the Hispanic population, as compared to the respective stages in the NHW. Ingenuity Pathway Analysis (IPA) was used to uncover significant DEGs associated with the S100 family signaling pathway in Hispanic CRC samples. Previous studies have indicated the involvement of the S100 family proteins and their signaling pathways in CRC development, progression, metastasis, and drug resistance through interactions with WNT/β-catenin, RAGE, MAPK and NF-κβ signaling pathways. Our investigation of DEGs within the S100 signaling pathway and their interaction with downstream effectors suggests differential expression of genes crucial in cellular processes, including matrix metallopeptidases (MMP), mitogen-activated protein kinases (MAP2K) and Wingless-related integration site (WNT) family proteins. Exploring these proteins and their downstream effectors in Hispanic CRC tissues and organoids would elucidate specific functional attributes influencing CRC progression. Understanding the interaction of proteins identified in this study may serve as potential ethnicity-specific biomarkers or targets for the development of novel therapeutic interventions for early-stage CRC diagnosis in Hispanics. Citation Format: Soumya Nair, Brian I Grajeda, Sourav Roy. The role of the S100 family signaling pathway proteins in Hispanic colorectal cancer disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C110.