Colorectal Mucinous Adenocarcinoma Research Articles

Syndrome de Stevens-Johnson induit par la capécitabine : à propos d’un cas avec revue de littérature

IntroductionCapecitabine is an oral fluoropyrimidine carbamate, analog of 5-fluorouracil. It is widely used for many malignant tumors. Hand-foot syndrome is the most common dermatological toxicity associated with capecitabine and Stevens-Johnson syndrome is the rarest manifestation. We report a case of Stevens-Johnson syndrome induced by capicitabine. Case presentationA 49-year-old patient, hospitalized in oncology for the management of a mucinous colorectal adenocarcinoma with peritoneal metastases. He was treated with capecitabine 3500mg per day. The patient presented diffuse pigmented lesions and an erosive scrotal lesion with dysphagia to solids and liquids, vomiting and non-bloody diarrhea, which occurred 5 days after the onset of the treatment. The clinical examination found an altered patient. The skin examination found a pigmented desquamative plaque on the face, diffuse atypical target lesions, a pigmented plaque on the palms of both hands, a scrotal erosion and cheilitis. The histology confirmed the diagnosis Stevens-Johnson syndrome. The pharmacovigilance declaration concluded that Stevens-Johnson syndrome was secondary to capecitabine according to chronological and bibliographic data. The patient died of respiratory distress. ConclusionStevens-Johnson syndrome is a rare and serious complication that can occur, rarely, in patients treated with capecitabine. Our case is the 5th case of capecitabine-induced SJS that has been reported in the literature since 2008.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts

AimsTo clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.MethodsImmunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18...

Mucinous Differentiation in Colorectal Cancer: A 10-Year Experience Audit at King Faisal Specialist Hospital and Research Centre, Jeddah.

Given that colorectal canceris one of the leading causes of mortality, mucinous adenocarcinoma is one of the subtypes and is characterized by the presence of mucin-producing tumor cells with mucin components and is more challenging to manage. In Saudi Arabia, it represents approximately 10-15% of all colorectal carcinoma.The main etiological cause of mucinous adenocarcinoma is yet not well understood. The main goal of our study is to discuss the histopathology and the molecular background of mucinous colorectal adenocarcinoma and also to provide an update on its prognosis and therapeutics from recent published literature. It is a retrospective cohort study that wasconducted at King Faisal Specialist Hospital, Jeddah, Saudi Arabia. The study included 68 adult patients diagnosed with mucinous colon cancer, who did surgical resection alone or with or without adjuvant chemotherapy following from January 2011 to December 2020. The mucinous subtypes are found more commonly in the proximal colon. In our study, 26 patients (38.2% of the cases) were right-sided and 35 patients (51.5%) were from the left side, but these included the rectum as well and this reflects the higher incidence of diagnosis of rectal cancer in the region. Most tumors were classified as Grade II in 56 patients (82.4%), consistent with the intermediate differentiation status often associated with the mucinous subtypes. The most common symptom at presentation was abdominal pain in 38 patients(55.9%) followed by per rectal bleeding and abdominal mass. The management in our study was in line with the standard established practice and surgical resection as expected was the primary potentially curative approach. Notably of patients presenting with locally advanced rectal cancer, six patients underwent concomitant chemoradiotherapy followed by surgery and four patients had upfront surgery. The duration of the median follow-up was 32 months. At the time of analysis, 30 patients (44.1%) were alive and remained on regular follow-up, 17 patients (25%) had succumbed to the disease, and 21 patients (30.9%) were lost to follow-up. The median overall survival was not reached, and notably, 49 patients (71.6%)remained alive at the four-year mark. Whilst our study contributes to the current understanding of mucinous adenocarcinomas of the colon, further research in molecular profiling and genomic testing and larger clinical trials with tailored treatments is necessary to refine treatment strategies and improve outcomes.

Pulmonary Recurrence of Colorectal Mucinous Adenocarcinoma and Sarcoidosis on 18 F-FDG PET/CT.

A 67-year-old woman, previously diagnosed with pulmonary sarcoidosis and sigmoid colon mucinous adenocarcinoma with pulmonary metastasis, showed an enlarged pulmonary nodule in routine follow-up. Because of the absence of treatment for either condition over the past 3 years, the nodule raised concerns of cancer recurrence or sarcoidosis progression. Its distinctive 18 F-FDG PET/CT appearance, compared with other pulmonary lesions, suggested a mucinous histology. The diagnosis was confirmed by pathological examination. This emphasizes the importance of knowledge of the 18 F-FDG PET/CT phenotype of neoplastic histological variants to address challenging diagnostic scenarios.

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer

Background and objectivesColorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature.MethodsCRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature.ResultsFrom the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients.ConclusionMAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.

Colorectal mucinous adenocarcinoma (MAC)is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC).This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs)between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

Clinicopathological characteristics and outcomes of colorectal mucinous adenocarcinoma: a retrospective analysis from China.

Mucinous adenocarcinoma (MAC) is a unique subtype of colorectal cancer and its prognostic value remains controversial. This study aimed to compare the clinicopathological characteristics and prognostic differences between patients with MAC and non-mucinous adenocarcinoma (NMAC). 674 patients with NMAC, 110 patients with adenocarcinoma with mucinous component (ACWM) and 77 patients with MAC between 2016-2019 were enrolled in the study. Univariate and multivariate Cox regression were performed to analyze the factors associated with prognosis. Predictive nomograms of overall survival (OS) and cancer-specific survival (CSS) for patients with colorectal adenocarcinoma were constructed. Confounding factors were eliminated by propensity score matching (PSM). Compared with patients with NMAC, patients with MAC were more likely to have a tumor located at the proximal colon, present with a larger tumor diameter, more advanced T stage, higher frequency of metastasis, deficiency of mismatch repair, and elevated preoperative carcinoembryonic antigen. Patients with MAC were related to worse OS (HR=2.53, 95%CI 1.73-3.68, p<0.01) and CSS (HR=3.09, 95%CI 2.10-4.57, p<0.01), which persisted after PSM. Subgroup analysis demonstrated that patients with left-sided or stage III/IV MAC exhibited a comparatively worse OS and CSS than those with NMAC. Furthermore, in patients with stage II with a high-risk factor and stage III MAC, adjuvant chemotherapy was associated with an improved OS, CSS, and RFS. Compared with the NMAC phenotype, the MAC phenotype was an independent risk factor for poor prognosis in colorectal adenocarcinoma with worse OS and CSS, particularly patients with left-sided colorectal cancer and stage III/IV. However, patients with MAC can still benefit from adjuvant chemotherapy.

Genomic comparison of urothelial mucinous adenocarcinoma and colorectal mucinous adenocarcinoma biomarkers and therapeutic implications.

650 Background: Urothelial mucinous adenocarcinoma (UC-MUC-AC), arising from the urothelium, is a rare condition (&lt;2%), typically presenting at an advanced stage with an unfavorable prognosis. The lack of a standard treatment protocol adds complexity, requiring the extension of treatments from UC or organ-specific MUC-AC such as colorectal. Notably, UC-AC bears a histopathological resemblance to intestinal tumors, constituting the predominant subtype. Alternatively, treatment decisions based on gene expression similarities in lieu of histological similarities are an evolving concept in rare cancers. This is an unexplored area in UC-MUC-AC treatment, prompting our hypothesis that an all-encompassing genomic profile could reveal analogous biomarkers shared with CRC-MUC-AC. Methods: Three techniques: DNA sequencing, RNA sequencing (WTS), and immunohistochemistry (IHC) sequencing (protein) with varying measures for gene expression were analyzed at Caris Life Sciences in Phoenix, AZ. Histopathology was used to categorize five cancer site groups: (1) UC arising in the bladder, ureter, urethra, or renal pelvis with any transitional cell carcinoma (TCC)-non-MUC-nonAC [N156 samples], (2) UC nonTCC-nonMUC-AC [N83], (3) UC-MUC-AC [N16], (4) CRC-MUC-AC [N3100] and (5) CRC nonMUC-AC [N38205]. Our primary aim was to determine which group was closest to Group 3, our control. Our secondary aim was to determine if Group 2 was genetically closer to Group 1 or 5. Only genes with positive expression were included in the cluster analysis. ANOVA analysis was conducted to further explore the relationships between the groups. A log transformation was performed to achieve normality. To further investigate pairwise comparisons, a post hoc Dunnett test was employed. Results: In our first analysis, Group 3 UC-MUC-AC gene expression ratio was predominately associated with UC Groups 1 &amp; 2 (24 of 33), and farther to CRC Groups 4 &amp; 5 (9/33) (all p-values &gt;0.05). In the second analysis, the ANOVA overall model comparing gene expression between the histological groups 1, 2 &amp; 5 was statistically significant (p=0.0018). The Dunnett test revealed a farther difference between Group 2, UC nonTCC-nonMUC adenocarcinoma, and 5, CRC non-MUC-AC (p-value =0.001), but closest between Group 2 and 1, UC-TCC-nonMUC-nonAC (p =0.100). Conclusions: Our findings indicate that next-generation sequencing technology has the potential to aid in treatment decisions based on the site of origin, such as UC-AC, rather than relying on traditional histopathological descriptive approaches for extrapolating evidence from treatment protocols used for other cancer origins like CRC. Future research on artificial intelligence could aid physicians with more informed treatment decisions by providing additional insight into how closely tumors match cancer types' genomic and transcriptomic signatures.

Mucinous Colorectal Adenocarcinoma on a 21-Year-Old Female. Case Report and Literature Review

Colon and rectal cancer is now the third most diagnosed in the West. About 40% of cases are diagnosed after age 75, and the incidence increases with age. Mucinous colorectal adenocarcinoma is a subtype of colon cancer. The effect of diet on the development of colon and rectal cancers is unclear. The clinical picture divides the colon into 2: Right-sided colon (cecum, ascending colon, hepatic flexure) versus the left-sided colon (splenic flexure, descending colon, sigmoid, rectosigmoid) and rectum. Arbitrarily, two-thirds of the transverse colon is on the right side. Patients are usually asymptomatic for the most part, when symptoms exist, they present as transrectal bleeding, changes in intestinal habits, anemia, or abdominal pain. In younger patients, additional factors are used to identify those at higher risk for colorectal cancer. (e.g., having a family history of colorectal cancer, changes in bowel habits, unexplained weight loss, and blood mixed with the stool instead of blood on the surface of the stool).

Location Has Prognostic Impact on the Outcome of Colorectal Mucinous Adenocarcinomas.

Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of tumors defined by extracellular mucin comprising more than 50% of the tumor. These tumors are on a continuum of mucin-producing malignancies with signet ring cell adenocarcinomas (SRCCs), which instead produce intracellular mucin. Mucin-containing cancers occur primarily in the stomach and colon, where for SRCCs, outcomes are relatively worse in the proximal stomach and the rectum. It is not known if MAs have similar outcomes. In this study, we use the Surveillance, Epidemiology, and End Results (SEER) database to examine the effects of tumor localization, age, sex, and stage on colorectal and gastric cancer outcomes for MAs. For right colon cancers, MAs are more common, particularly in females, and have slightly better or equivalent outcomes across all stages and ages compared to conventional adenocarcinomas, but outcomes are progressively worse compared to conventional adenocarcinomas for left colon and rectal cancers. Unlike SRCCs, MAs have similar outcomes to conventional adenocarcinomas in all stomach locations. Overall, these results suggest that MAs have an intrinsically different tumor biology in the left colon and rectum that promotes pathogenesis. Decoding this phenomenon could lead to more effectively tailored patient treatment regimens.

Survival Benefit of Primary Tumor Resection Combined With Chemotherapy in Patients With Unresectable Colorectal Mucinous Adenocarcinoma With Liver Metastasis.

To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.

S2298 An Unusual Presentation of the Brain Metastasis From Mucinous Colorectal Adenocarcinoma With KRAS Mutation Presenting as Seizures

S2298 An Unusual Presentation of the Brain Metastasis From Mucinous Colorectal Adenocarcinoma With KRAS Mutation Presenting as Seizures

Pictilisib-Induced Resistance Is Mediated through FOXO1-Dependent Activation of Receptor Tyrosine Kinases in Mucinous Colorectal Adenocarcinoma Cells.

The phosphatidylinositol (PI3K)/AKT/mTOR axis represents an important therapeutic target to treat human cancers. A well-described downstream target of the PI3K pathway is the forkhead box O (FOXO) transcription factor family. FOXOs have been implicated in many cellular responses, including drug-induced resistance in cancer cells. However, FOXO-dependent acute phase resistance mediated by pictilisib, a potent small molecule PI3K inhibitor (PI3Ki), has not been studied. Here, we report that pictilisib-induced adaptive resistance is regulated by the FOXO-dependent rebound activity of receptor tyrosine kinases (RTKs) in mucinous colorectal adenocarcinoma (MCA) cells. The resistance mediated by PI3K inhibition involves the nuclear localization of FOXO and the altered expression of RTKs, including ErbB2, ErbB3, EphA7, EphA10, IR, and IGF-R1 in MCA cells. Further, in the presence of FOXO siRNA, the pictilisib-induced feedback activation of RTK regulators (pERK and pAKT) was altered in MCA cells. Interestingly, the combinational treatment of pictilisib (Pi3Ki) and FOXO1i (AS1842856) synergistically reduced MCA cell viability and increased apoptosis. These results demonstrate that pictilisib used as a single agent induces acute resistance, partly through FOXO1 inhibition. Therefore, overcoming PI3Ki single-agent adaptive resistance by rational design of FOXO1 and PI3K inhibitor combinations could significantly enhance the therapeutic efficacy of PI3K-targeting drugs in MCA cells.

Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma.

Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC. Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry. We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated. We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.

FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma

Mucinous colorectal adenocarcinoma (MC) is less likely to respond to chemotherapy and is associated with poorer prognosis compared with non-MC (NMC). Fibroblast activation protein (FAP) was found and validated to be upregulated in MC patients and was negatively correlated with prognosis and therapeutic outcomes in colorectal cancer (CRC) patients who were treated with adjuvant chemotherapy. Overexpression of FAP promoted CRC cell growth, invasion and metastasis, and enhanced chemoresistance. Myosin phosphatase Rho-interacting protein (MPRIP) was identified as a direct interacting protein of FAP. FAP may influence the efficiency of chemotherapy and prognosis by promoting the crucial functions of CRC and inducing tumor-associated macrophages (TAMs) recruitment and M2 polarization through regulating theRas Homolog Family Member/Hippo/Yes-associated protein (Rho/Hippo/YAP) signaling pathway. Knockdown of FAP could reverse tumorigenicity and chemoresistance in CRC cells. Thus, FAP may serve as a marker for prognosis and therapeutic outcome, as well as a potential therapeutic target to overcome chemoresistance in MC patients.

Prognostic significance of mucinous histology in left‑sided metastatic colorectal cancers with wild‑type RAS and evaluation of backbone chemotherapy regimens.

Mucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.

Molecular characterization of colorectal mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, identified by multiomic data analysis.

Adenocarcinoma not otherwise specified (AC) and mucinous adenocarcinoma (MC) have different biological behaviors and clinical features. We utilized our previous proteomic data and public transcriptome, single-cell transcriptome, and spatial transcriptome databases to profile the molecular atlas of the tumor microenvironments of MC, AC, and normal colon tissues. By exploring the general and specific molecular features of AC and MC, we found that AC was immune-active but exposed to a hypoxic microenvironment. MC cells could protect against DNA damage, and the microenvironment was unfavorable to leukocyte transendothelial migration. We identified several potential molecular and cellular targets of AC and MC for future research. We also highlighted that the major difference between AC and MC was not the variety of cell types and functions but possibly cell interactions. Stromal and epithelial cell interactions play important roles in both MC and AC, but different regulatory pathways were involved.

Abstract 1750: Removal of mucin glycans by Bifidobacterium bifidum enhances chemotherapy-mediated cell death in mucinous adenocarcinomas

Abstract Background: Mucinous colorectal adenocarcinoma, a subtype of colorectal cancer, is characterized by mucin production and increased resistance to several chemotherapeutic interventions; resulting in a poorer prognosis compared to non-mucus secreting cancers. Advances in treatment are stymied by the limited number of efficacious chemotherapeutic agents. The most common drug used to treat colorectal cancer is 5-Fluorouracil (5-FU), but less than 10% of mucinous tumors respond to this drug. The production of mucus has been theorized to limit the uptake of chemotherapeutic agents via charge repulsion and size exclusion, thereby promoting chemo-resistance and driving poor outcomes. Hypothesis: We predict that mucin-degrading microbes secrete glycosyl hydrolase enzymes which cleave mucin glycans and promote the uptake of chemotherapeutic agents and enhance cell death. Methods &amp; Results: We queried the human gut microbiota and identified multiple diverse microbes which encode enzymes to degrade mucin glycans. Among the mucin-degrading bacteria, we found that Bifidobacterium bifidum harbored one of the most extensive repertoires of mucin-degrading enzymes. B. bifidum was grown in a chemically defined medium with or without porcine intestinal mucus and the secreted products were then added to mucus-producing adenocarcinoma cell lines: HT29-MTX and T84 cells. Supernatant from cultures with mucus removed sialic acid residues and enhanced 5-FU uptake after 48 hrs in both cell lines. Supernatant without mucus also promoted 5-FU mediated cell death; although to a lesser degree than supernatant from cultures incubated with mucus. Gene expression analysis and immunostaining revealed decreased MUC13 gene expression and protein in B. bifidum metabolite treated cell lines compared to media controls. In contrast, we found that secreted products from B. dentium, which is unable to degrade mucus, had no effect on 5-FU induced cell death. Conclusions: Our data suggests that B. bifidum elicits chemo-sensitivity via the production of mucin-degrading enzymes, which cleave negatively charged sialic acid, increasing the activity of 5-FU in these cancers as well as by lowering the expression of adherent mucins. This work points to a novel role of mucin-degrading microbes to promote 5-FU penetration of mucinous colorectal adenocarcinoma. This strategy has the potential to provide unique treatment strategies for patients with mucinous colorectal cancer. Citation Format: Leah K. Stripe, Amy C. Engevik, Mindy A. Engevik. Removal of mucin glycans by Bifidobacterium bifidum enhances chemotherapy-mediated cell death in mucinous adenocarcinomas [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 1750.

Immunophenotypic profiles and prognosis for colorectal mucinous adenocarcinomas are dependent on anatomic location.

The prognostic value of mucinous adenocarcinomas (MCAs, exhibiting >50% extracellular mucin) of the colorectum, in relation to their anatomic location is not well studied. We compared MCAs (n= 175) with non-MCAs (NMCAs, n= 1015) and the cancer-specific survival rates were evaluated, based on their anatomic site, by univariate Kaplan-Meier and multivariate Cox methods. Subsets of these tumors were immunostained for MUC1, MUC2, Bcl-2, and p53. MCAs were more commonly found in the right colon, were of high-grade, and were more prevalent in younger patients (<40 years). They exhibited strong expression of MUC2 and Bcl-2 and showed less p53 nuclear staining. In contrast, most NMCAs were low-grade with high expression of MUC1. MCAs of the rectum were associated with poorer outcomes relative to NMCAs (HR 1.85, CI 95% 1.15-2.97), even though the distributions of advanced-stage tumors were similar. Late-stage disease and age were poor independent prognostic indicators of cancer-specific deaths across all tumor locations. In summary, rectal MCAs have a poor prognosis.

A prognostic nomogram for predicting overall survival in colorectal mucinous adenocarcinoma patients based on the SEER database.

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.