Abstract Background: Thirty years ago, a S1P/ceramide “sphingosine rheostat” model was proposed based on ceramide’s pro-apoptotic vs. sphingosine-1 phosphate (S1P) pro-survival role, where in cancer, the rheostat tilts towards enhanced synthesis of S1P from ceramides, increasing the ratio. Human tumor data supporting the hypothesis, however, are very limited. Objective: To leverage quantitative multi-omics to explore the balance in the synthesis of lipids within the S1P/Ceramide metabolic pathway in a large set (n = 629) of human colorectal cancers (CRC).Design Quantitative LC-MS/MS analysis was performed on 525 primary and 104 metastatic CRC (mCRC). An integrative multi-omics analysis combining quantitative lipidomics with whole transcriptomics, quantitative RT-PCR of selected genes and clinical data was completed. Results: We demonstrated that mCRC versus primary specimens are relatively enriched in S1P and sphinganine-1-P (Sa1P), whereas the long chain ceramides (24:1) are relatively decreased. Gene-expression analysis of a large (n = 2200) CRC patient dataset and qRT-PCR of CRC revealed that S1P/Sa1P-synthesizing enzymes and their receptors are enriched in mCRC and are linked to poor prognosis. scRNA-seq analysis showed that their expression prevailed in myeloid cells. Finally, a three-gene S1P macrophage-associated signature correlated with stage and patient survival. Conclusion: Our findings define an imbalance in the synthesis of S1P/Ceramide linked to poor prognosis and cancer progression, and attributable to proinflammatory macrophages in the tumor microenvironment, validating the sphingosine rheostat hypothesis in mCRC. Citation Format: Michelle M. Maurin, Siddabasave Gowda B. Gowda, Divyavani Gowda, Heiman Wang, Michael Nebozhyn, Ramani Soundararajan, Mckayla Carr, Punith M Sundaraswamy, Ashley Alden, Carolina Martinez, Robert David Bennett, Allen Chudzinski, Andreas Karachristos, Timothy M. Nywening, Paul M. Cavallaro, Matthew Linley Anderson, Robert J. Coffey, Michael Schell, Jorge Marcet, Richard Jacobson, Andrey Loboda, Ganesh V. Halade, Mingli Yang, Lance Pflieger, Warren Jackson Pledger, Shu-Ping Hui, Timothy J. Yeatman. Multiomics integration unveils a shifted balance in the sphingosine-1 phosphate/ceramide rheostat fueled by macrophage immunosuppression in metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6126.

EGFR inhibitor (EGFRi) therapies have been FDA-approved for metastatic colorectal cancer (CRC). However, extended RAS/RAF testing required in the drug labels, identifies only non-responders, and only 50

Abstract Introduction: We recently reported (Soundararajan et. al., GUT, 2024) a strong pro-inflammatory lipid mediator bias in colorectal cancer (CRC), possibly related to the omega-6 rich fatty acid preponderance in western-style diets. The current project expands on those findings, linking omega-6 fatty acids to expression of inflammatory genes in human CRC and mouse models. Method: We performed an integrative, multi-omics, weighted gene co-expression network analysis (WGCNA) of 25 quantified arachidonic acid-derived lipid mediators with whole transcriptomes from 293 primary and 77 metastatic human CRCs, to identify a lipid-gene module significantly associated with metastasis. In mice fed omega-6:omega-3 (10:1 w/w) vs. control (1:1 w/w) diets, we analyzed syngeneic CRC subcutaneous tumors using whole transcriptome RNA-sequencing. THP1-derived gene expression signatures for M0, M1 and M2 macrophages were correlated with the lipid-gene module. Results: In the human tumors using an unsupervised analysis, we identified a pro-inflammatory lipid-gene module, linked to the clinical feature of metastasis (P< 1.1e-42), with prominence of “hallmark” genes linked to coagulation, complement, inflammation and EMT/tumor progression and associated with M1 macrophages. Analysis of murine tumors derived from animals fed a diet enriched with omega-6 fatty acids revealed a significant (p < 3.7329E-06), shared enrichment of 18 coagulation and EMT related genes --orthologous to those identified in the pro-inflammatory human lipid-gene module. Among the 18 genes, SerpinA1b, SerpinA1d, SerpinA3k, Ambp and Plg with anti-inflammatory and coagulation- inhibitory properties were downregulated in omega-6 fed mice. Moreover, we observed a dramatic decrease in Serpina1 protein expression in the hepatic sinusoids in omega-6 mice. Conclusion: A human tumor pro-inflammatory lipid-gene module was identified, and its gene expression was shared with tumors derived from mice fed with an omega-6-rich diet. Hallmark gene analysis found inflammation and deranged coagulation prominent. In omega-6 fed mice, decrease in Serpina1 protein expression in liver sinusoidal endothelial cells---the first target of metastasizing cells---suggests localized inflammation with enhanced coagulation. Collectively, these data suggest omega-6 enriched murine and human western diets may foster the development of an inflammatory, coagulopathic pre-metastatic liver niche, with M1 macrophages as the main contributors of CRC inflammation. Citation Format: Ramani Soundararajan, Lance Pflieger, Gunjan Upadhyay, Michelle M. Maurin, Mingli Yang, Michael Schell, McKayla Carr, Ahalya Sekhar, Rachel Kenis, Heiman Wang, Michael Nebozhyn, Andrey Loboda, Aejaz Nasir, W Jack Pledger, Ganesh V. Halade, Timothy J. Yeatman. Omega-6 lipid-gene module linked to colorectal cancer pre-metastatic niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6156.

Recently, we serendipitously identified a pair of distinct 10-gene signatures, one associated with epithelial cells (EPIS) and one the tumor microenvironment(TMES). When we classified 2373 colorectal cancer (CRC) tumors into the consensus molecular subtypes (CMS1-4), the EPIS signature score was predominantly related to the TME-poor CMS2/CMS3 classes and was highly predictive of EGFRi outcomes in two clinical trial datasets and a large, real-world clinico-genomics dataset. By contrast, the TMES signature score was strongly associated with the immune/stromal CMS1/CMS4 subtypes and was highly correlated with the gene expression signature scores portending EMT, SRC activation and MEK inhibitor resistance (MEKi-R). To understand the cellular features underpinning the TMES correlation, we further analyzed the cellular origins of 61 SRC signature genes and 13 MEKi-R signature genes, as well as 8 EMT genes using an independent public scRNASEQ dataset (n=62). All of the 13 MEKi-R genes and all of the 8 EMT genes, as well as most of the SRC activation genes, were predominantly expressed in various immune/stromal TME cells, supporting a key role of the TME gene expression. Remarkably, when the signature scores were analyzed in a dataset of ∼150 heterogenous CRC cell lines that do not have a TME, a similar strong correlation among the TMES, EMT, SRC activation and MEKi-R scores was also observed. These data suggest that the CRC epithelial cells may have adopted the TME gene expression features important in modulating the drug sensitivities. Spatial transcriptomics of 8 CRC samples confirmed that the EPIS genes were predominantly expressed in epithelial cells. By contrast, the signature genes of the TMES linked to EMT/SRC activation/MEKi-R were diffusely expressed across epithelial/invasive cancer mixed with the TME, indicating an interactive tumor-TME cellular feature. Our data suggest that the TME through its impact on epithelial cell gene expression may define drug sensitivities to targeted therapies. Mingli Yang, Michael V. Nebozhyn, Lance Pflieger, Ramani Soundararajan, Michelle Maurin, Heiman Wang, Andrey Loboda, W. Jack Pledger, Timothy J. Yeatman. Tumor cell expression of a distinct TME gene signature defines differential drug sensitivities to EGFR/MEK/SRC targeted agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5112.

Background Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4).Objective We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation.Design We performed liquid chromatography and tandem mass spectrometry (LC-MS/MS) untargeted analysis of 40 human CRC and normal paired samples and targeted, quantitative analysis of 81 human CRC and normal paired samples. We integrated analysis of lipidomics, quantitative reverse transcription-PCR, large scale gene expression, and spatial transcriptomics with public scRNASEQ data to characterize pattern, expression and cellular localisation of genes that produce and modify lipid mediators.Results Targeted, quantitative LC-MS/MS demonstrated a marked imbalance of pro-inflammatory mediators, with a dearth of resolving lipid mediators. In tumours, we observed prominent over-expression of arachidonic acid derivatives, the genes encoding their synthetic enzymes and receptors, but poor expression of genes producing pro-resolving synthetic enzymes and resultant lipoxins (LXA4, LXB4) and associated receptors. These results indicate that CRC is the product of defective lipid class switching likely related to inadequate or ineffective levels of PGE2/PGD2.Conclusion We show that the lipidomic profile of CRC tumours exhibits a distinct pro-inflammatory bias with a deficiency of endogenous resolving mediators secondary to defective lipid class switching. These observations pave the way for 'resolution medicine', a novel therapeutic approach for inducing or providing resolvins to mitigate the chronic inflammation driving cancer growth and progression.

Accumulating evidence has suggested that cancer progression and therapeutic response depend on both tumor epithelium (EPI) and tumor microenvironment (TME). However, the dependency of clinical outcomes on the tumor EPI vs. the TME has neither been clearly defined nor quantified. We classified 2373 colorectal cancer (CRC) tumors into the consensus molecular subtypes (CMS1-4) and generated the 10-gene TMES and the 10-gene EPIS signatures as the serendipitous derivatives of the most (positively vs. negatively) correlated genes of a highly-prognostic, 500-gene signature we previously identified. Distinct TME vs. EPI cellular features of the signature genes were identified by CIBERSORT deconvolution and validated by scRNASEQ in an independent public dataset. The TMES signature was strongly associated with the immune/stromal TME-rich CMS1/CMS4 subtypes that portended worse survival, whereas the EPIS signature was predominantly related to the TME-poor, epithelial CMS2/CMS3 classes that portended better survival. Multivariable Cox regression analysis against 29 TME-related signatures revealed that the TMES signature was the most strikingly impacted by the “Cancer-associated fibroblasts” signature (HR: 10.87 vs. 0.13, both P < 0.0001). Moreover, the TMES score was strongly correlated with EMT, SRC activation and MEK inhibitor resistance in 2373 CRC tumors (Spearman r = 0.727, 0.802, 0.824, respectively), which was validated in two independent CRC datasets (n = 626 and n = 566). By contrast, the EPIS score was the dominant force in associating with longer progression free survival in cetuximab-treated metastatic CRC patients derived from two independent clinical trials (Logrank trend P = 0.0005/n = 80; P = 0.0013/n = 44). This finding was further validated in a large real-world clinico-genomics dataset with EGFR inhibitor therapy, which demonstrated that higher EPIS scores were associated with increased overall survival (EGFRi, Logrank trend P < 0.0001/n = 2343) and time on treatment (cetuximab, P = 0.003/n = 953; panitumumab, P < 0.0001/n = 1307). Here we identified a pair of new, distinct 10-gene signatures (the EPIS vs. the TMES) capable of distinguishing the cellular contribution of the tumor EPI vs. the TME in determining CRC prognosis and therapeutic outcomes. With targeted approaches emerging to address both tumor epithelial cells and the TME, the EPIS vs. TMES signature scores may have a novel biomarker role to permit optimization of CRC therapy by identifying sensitive vs. resistant subpopulations.

203 Background: Cetuximab (CTX) and Panitumumab (PMB) therapies directed at EGFR have been restricted to left-sided CRC harboring wild-type KRAS ( KRASWT), limiting their utility. Approximately 50% of mCRC fail to respond to EGFRi, thus identification of predictive biomarkers is an unmet need. Here we evaluate a CTX sensitivity score (CTX-S) that we previously reported (Yang M. et al., 2019), in a large, real-world population of RAS/BRAF mutant vs wild-type and in right- vs left-sided tumors. Methods: CTX/PMB-treated CRC specimens (n=1124) with clinical outcomes, NextGen Sequencing of DNA (592-gene panel or whole exome sequencing) and RNA (whole transcriptome sequencing) were tested at Caris Life Sciences (Phoenix, AZ). 1097 specimens were MSS as determined by IHC of MMR proteins and/or NGS. Association of CTX-S with RAS/BRAF mutation and tumor sidedness was performed in MSS tumors. Tumors with likely pathogenic mutations in KRAS, NRAS or BRAF were considered as RASMUT /BRAFMUT, or RASWT /BRAFWT if no mutation was detected for each gene. Samples were stratified based on CTX-S quintiles. Survival on EGFRi was calculated from the initiation of EGFRi to last contact using Kaplan-Meir method. Results: Higher CTX-S quintiles were significantly associated with longer survival on EGFRi in RAS/BRAF wild-type as well as -mutant subpopulations. Similar results were seen in left- vs. right-sided tumors (Table). Higher CTX-S quintiles were associated with a survival benefit in all CMS classes but CMS2; however, the vast majority of CMS2 tumors (460/467) were among the top 3 CTX-S quintiles. As the median survival among the top 3 quintiles was ~2-fold higher than the bottom 2 quintiles, we used stratification by the 40th percentile for the genomic analysis. CTX-S >40th percentile was associated with an increased prevalence in APC (91 vs 47%) and TP53 (93 vs 76%) mutations and decreased prevalence in BRAF (6 vs 32%), SMAD4 (8 vs 19%), RNF43 (1 vs 12%) and ATM (2 vs 5%) mutations (all q<0.05). Conclusions: Our data suggest that CTX-S may predict longer survival on EGFRi, surprisingly independent of RAS/BRAF mutation status as well as tumor sidedness. Patients with high CTX-S had increased prevalence of CMS2 and harbored more APC and TP53 mutations. A strong EGFRi biomarker would likely expand the utility of EGFRi to right-sided tumors and possibly to RASMUT tumors. Further validation of these biomarkers in a prospective clinical trial is warranted and could change our current standard of care for CRC.[Table: see text]

Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after myocardial infarction (MI), in contrast to proinflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in patients with STEMI who undergo PCI. In this prospective observational clinical study, patients with STEMI (n = 10) and control subjects (n = 6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2-, and 24-h post-PCI. A total of 10 patients with STEMI received PCI with a mean age of 53.3 yr, 90% male. Linoleic acid and docosapentaenoic acid levels were higher in patients with STEMI. A subset of PIM levels [hydroxyeicosatetraenoic acids, prostaglandin (PG)E2] was elevated at the baseline, with a subsequent decrease in circulating levels at 2 h after PCI [thromboxanes, leukotriene B4 (LTB4), 20-hydroxy-LTB4]. A subset of SPM levels was elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of lipid mediators showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating patients with MI. NEW & NOTEWORTHY Polyunsaturated fatty acids-derived SPMs are decisive in myocardial infarction (MI) recovery, contrasting with proinflammatory lipid mediators (PIMs). A study on early lipid changes post-percutaneous coronary intervention (PCI) in patients with STEMI shows baseline elevation and post-PCI decrease in PIMs, whereas some SPM levels remain elevated. Findings highlight simultaneous inflammation and resolution in STEMI, emphasizing the need to enhance endogenous repair processes before PCI for better MI treatment.

Abstract Accumulating evidence has suggested that cancer progression and therapeutic response may depend on not only tumor cells but also their tumor microenvironment (TME). However, their contributory roles are complex and not well understood. Here we report an analysis of 2373 human colorectal cancer (CRC) tumors representing all stages, leading to identification of a 20-gene signature capable of quantifying the cellular contribution of the tumor vs. the TME in determining colorectal cancer prognosis and therapeutic outcome. We classified these tumors into the consensus molecular subtypes (CMS1-4) with distinct, variable TME cellular features defined by CIBERSORT deconvolution analysis of bulk gene expression data. Surprisingly, all the 10 positive signature genes (portending worse survival) were strongly correlated with the TME-rich CMS1 and CMS4 tumors. By contrast, all the 10 negative signature genes (portending better survival) were highly related to the TME-poor CMS2 and CMS3 tumors. A single cell expression analysis from an independent database further revealed that strikingly, all the 10 positive genes were principally expressed by the immune/stromal TME whereas all the 10 negative genes were predominantly expressed in epithelial tumor cells. These data suggest that the TME has an equally important role as do tumor cells in determining CRC prognosis and support targeting the TME to improve survival. Moreover, distinct gene expression from tumor cells versus the TME also showed a differential impact on therapeutic outcome. Retrospective analyses on two independent clinical trial datasets show that the 20-gene signature score significantly predicted progression free survival in metastatic CRC patients treated with cetuximab, an FDA-approved EGFR inhibitor therapy. These data suggest a potential for the 20-gene signature as a predictive biomarker to identify “sensitive” versus “resistant” subpopulations of CRC patients to improve outcome of EGFR-targeted therapy. Citation Format: Mingli Yang, Timothy J. Yeatman, Michael V. Nebozhyn, Michael J. Schell, Lance Pflieger, Andrey Loboda, Warren J. Pledger, Ramani Soundararajan, Michelle Maurin, Heiman Wang, Jetsen Rodriguez Silva, Ashley Alden. Gene expression signature quantifies the cellular contribution of the tumor vs. the microenvironment in determining colorectal cancer prognosis and therapeutic outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6430.

56 Background: Although, EGFRi including Cetuximab (CTX) and Panitumumab (PMB) is restricted to KRAS wild-type ( KRASWT) tumors, ~50% of patients still fail to respond to therapy. Using a transcriptional signature as a surrogate for cetuximab response, we previously reported that mutations in APC ( APCMUT) and TP53( TP53MUT) might predict cetuximab sensitivity, particularly in RASWT tumors (Yang M. et al., 2019). The current study aimed to use real world EGFRi treatment and survival data to independently validate these mutations as predictive, high-utility biomarkers of benefit to specific subpopulations of CRC. Methods: CTX/PMB-treated CRC specimens (n=1846) with clinical outcomes and NextGen Sequencing of DNA (592-gene panel or whole exome sequencing) were tested at Caris Life Sciences (Phoenix, AZ). All analyses were performed in MSS tumors, determined by immunohistochemistry of MMR proteins and/or NGS. Tumors with likely pathogenic mutations in KRAS, NRAS or BRAF were considered as RASMUT /BRAFMUT, or RASWT /BRAFWT if no mutation was detected for each gene. Survival on EGFRi was calculated from the initiation of EGFRi to last contact (E-OS) or last dose of EGFRi (E-TOT) using Kaplan-Meir method. Results: While concurrent TP53MUT/ APCMUT were associated with improved E-OS compared to TP53MUT alone (hazard ratio [HR]=0.565, p<0.00001), APCMUT tumors were associated with improved E-OS independent of TP53 mutation status. Compared to APCWT, APCMUT were associated with longer E-OS in RAS/BRAF mutant as well as wild-type subpopulations and in left- and right- sided tumors. Furthermore, APCMUT were associated with improved E-TOT in PMB treated tumors independent of RAS/BRAF mutation status and tumor sidedness (HR range:0.59-0.75, all p<0.05). Conclusions: Our data suggests that the simple application of a high-utility mutational biomarker ( APC), may increase the eligibility for successful EGFRi therapy in a substantial subpopulation of RAS/BRAF mt patients as well as right-sided CRC, potentially altering the standard of care. Further validation of this biomarker in a prospective clinical trial is warranted. [Table: see text]

Supplementary Figures 1-3 from Epithelial Progeny of Estrogen-Exposed Breast Progenitor Cells Display a Cancer-like Methylome

Two well-characterized EGFR inhibitor (EGFRi) therapies (cetuximab, panitumumab) have been FDA approved for metastatic colorectal cancer (CRC). Unfortunately, the extended RAS/RAF testing required in the drug labels, identifies only non-responders, and only ~50% of treated patients will respond to therapy. Thus, there is an unmet need to develop additional biomarkers to identify EGFRi sensitive patients. Using an innovative hybrid approach fusing gene expression and DNA sequencing, we recently reported that combined mutations in APC and TP53 were strongly correlated with a validated gene expression signature measuring cetuximab sensitivity in CRC human tumors (Yang et al. Cancer Epidemiol Biomarkers Prev. 2019), suggesting a potential positive biomarker role of APC + TP53 mutations. This finding prompted us to develop a DNA test designed to positively select EGFRi-responsive patients as augmentation to currently used negative predictors for CRC patients. By leveraging the TwinStrand Duplex Sequencing (DS) technology, we recently developed an ultrasensitive custom 6-gene panel (APC, TP53, KRAS, BRAF, NRAS, and HRAS) CLIA-certified assay for FFPE CRC tissues. The assay has been analytically validated using reference cell lines (n=10) which were individually sequenced to >3,000x Duplex depth. The 6-gene DS assay yielded exceptionally high assay performance: (1) accuracy (passed, r2 = 0.98 for Duplex VAF vs. target VAF for Positive Control mutations); (2) sensitivity (passed, all mutations >1/5,000 were detected in all Positive Control replicates; 1 mutation at 1/5,000 was detected in 2/3 replicates), (3) specificity (passed, 2 mutations detected in the Negative Control at 1 count in 1 replicate; VAF <1/10,000), and (4) precision (passed, <2-fold variation among Positive Control replicates for VAF >1/500). Importantly, the validation analysis on fresh frozen (FF):FFPE paired tissues from 21 CRC patients shows: (1) The 6-gene DS assay performed on FFPE samples faithfully reproduces assay results on FF samples; (2) The ultrasensitive DS assay can accurately detect additional “new” mutations at low allelic frequencies compared to a standard NGS method. TwinStrand DS identified 17 mutations not identified by standard NGS; 13 of these new mutations had < 10% VAF. Furthermore, preliminary Kaplan-Meier analysis of the third-line EGFRi data shows that while the statistical significance was not achieved due to the small simple size (n=28), patients harboring combined APC and TP53 mutations(AP) (vs non-AP patients) tended to have longer progression free survival (6.65 vs 3.95 months, P=0.064) and overall survival (17.80 vs 10.65 months, P=0.14). Additional data acquisition and analysis is ongoing. Thus, there is an opportunity to change clinical practice and standards of care to ultimately improve CRC outcomes if this new, robust, sensitive test is clinically-validated. Citation Format: Mingli Yang, Michael J. Schell, Lance Pflieger, Jesse Salk, Timothy J. Yeatman. Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to EGFR inhibitors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4343.

Supplementary Data from Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer

Supplementary Figures and Tables

Supplementary Figure 1 from Mapping Geographic Zones of Cancer Risk with Epigenetic Biomarkers in Normal Breast Tissue

Supplementary Figures 1-3, Tables 1-2 from Downregulation of Notch Pathway by a γ-Secretase Inhibitor Attenuates AKT/Mammalian Target of Rapamycin Signaling and Glucose Uptake in an ERBB2 Transgenic Breast Cancer Model

Supplementary Data from DNA Copy-Number Alterations Underlie Gene Expression Differences between Microsatellite Stable and Unstable Colorectal Cancers