MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Peng, Lisha; Chang, Jiang; Li, Xilin; Lu, Shiying; Ren, Hong-Lin; Zhou, Xiaoqin; Liu, Zengshan; Hu, Pan

doi:10.3390/cimb43030108

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…29 While it remains unclear whether MC1R overexpression is mechanistically important in melanoma, impaired MC1R function is linked to heightened skin cancer susceptibility and its variants have been explored as prognostic markers in metastatic melanoma and colorectal cancer. 30,31 Our study underscores the potential of MC1R as a prognostic marker for death among patients with resected primary melanoma, a finding of particular relevance in the contemporary era with the wide adoption of adjuvant therapies. Markers of poor prognosis might enable us to preferentially treat those at higher risk of death.…”

Section: Mc1r Expression and Clinicopathologic Featuresmentioning

confidence: 66%

Melanocortin 1 receptor (MC1R) expression as a marker of progression in melanoma

Su,

Djureinovic,

Schoenfeld

et al. 2023

Preprint

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Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in melanoma patients, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking. Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression. We show a stepwise elevation of MC1R expression in different stages of melanoma progression (nevi, primary, metastasis). Higher MC1R expression was seen in deeper (>1 mm) primary lesions, ulcerated lesions, and mucosal melanomas compared to cutaneous melanomas and was associated with shorter survival in primary and metastatic tumors. On multi-variable analysis, Breslow thickness, ulceration, male sex, and chronic sun exposure were independent predictors of worse overall survival in the primary melanoma cohort. In the metastatic melanoma cohort, MC1R expression and mucosal melanomas were independent predictors of inferior overall survival. Our data suggest that MC1R might be a valuable drug target in aggressive melanoma. Additional studies are warranted to determine its functional significance in melanoma progression and its utility as a predictive biomarker in patients receiving MC1R-directed therapies.

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Section: Mc1r Expression and Clinicopathologic Featuresmentioning

confidence: 66%

Melanocortin 1 receptor (MC1R) expression as a marker of progression in melanoma

Su,

Djureinovic,

Schoenfeld

et al. 2023

Preprint

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“…Recent studies have shown that MC1R is involved in the initiation and progression of colorectal cancer [ 43 ]. Our results show that MC1R was highly expressed in 2D colon cancer cell lines and organoids, and the trend was more obvious in organoids.…”

Section: Resultsmentioning

confidence: 99%

A Self-Assembling Peptide as a Model for Detection of Colorectal Cancer

Wan

Luo

et al. 2022

Gels

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Patient-derived organoid (PDO) models have been widely used in precision medicine. The inability to standardize organoid creation in pre-clinical models has become apparent. The common mouse-derived extracellular matrix can no longer meet the requirements for the establishment of PDO models. Therefore, in order to develop effective methods for 3D cultures of organoids, we designed a self-assembling peptide, namely DRF3, which can be self-assembled into ordered fibrous scaffold structures. Here, we used the co-assembly of self-assembling peptide (SAP) and collagen type I, fibronectin, and laminin (SAP-Matrix) to co-simulate the extracellular matrix, which significantly reduced the culture time of PDO, improved the culture efficiency, and increased the self-assembly ability of cells. Compared with the results from the 2D cell line, the PDO showed a more significant expression of cancer-related genes. During organoid self-assembly, the expression of cancer-related genes is increased. These findings provide a theoretical basis for the establishment of precision molecular modeling platforms in the future.

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“…MC1R promotes UV-induced DNA damage repair ( 45 ), and its frequent mutations are associated with an increased risk of CRC ( 46 ). In contrast, CCL24 is highly expressed in patients with CRC, is associated with a better prognosis ( 47 ), and specifically induces M1 macrophage chemotaxis ( 48 ). LGALS2 is an oxidative stress-responsive gene that inhibits colon tumor growth ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma

Liang

Sun

et al. 2022

Front. Immunol.

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IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy.

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MC1R Is a Prognostic Marker and Its Expression Is Correlated with MSI in Colorectal Cancer

Cited by 7 publications

References 49 publications

Melanocortin 1 receptor (MC1R) expression as a marker of progression in melanoma

Melanocortin 1 receptor (MC1R) expression as a marker of progression in melanoma

A Self-Assembling Peptide as a Model for Detection of Colorectal Cancer

Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma

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