MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer

Nishiuchi, Aya; Hisamori, Shigeo; Sakaguchi, Morihiko; Fukuyama, Keita; Hoshino, Nobuaki; Itatani, Yoshiro; Honma, Shusaku; Maekawa, Hirofumi; Nishigori, Tatsuto; Tsunoda, Shigeru; Obama, Kazutaka; Miyoshi, Hiroyuki; Shimono, Yohei; Taketo, Makoto Mark; Sakai, Yoshiharu

doi:10.3390/cancers11121891

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…This may be why the incidence reported in early-stage CRC is so low and difficult to assess. Regardless, our findings are in line with those of other publications [ 50 , 68 , 84 ]. As mentioned, the prognostic value of CDX2 is most often described in poorly differentiated tumors, but it is not so clear for well-differentiated or stage II and III tumors [ 68 , 85 , 86 ].…”

Section: Discussionsupporting

confidence: 94%

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

Azcue

Setas

Encı́o

et al. 2021

Cancers

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Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early-stage colon cancer (CC). The purpose of this study was to assess PD-L1, GLUT-1, e-cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk-panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD-L1, GLUT-1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low-risk patients, medium-risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high-risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early-stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.

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Section: Discussionsupporting

confidence: 94%

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

Azcue

Setas

Encı́o

et al. 2021

Cancers

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“…It was reported that CDX2 loss does not confer a worse prognosis when considering MMR-deficient cases [ 46 ], although it predicted poor clinical outcome in stage II CRC cases with MSS phenotype [ 45 ]. According to previous studies that included stage II and stage III CRC cases [ 18 , 24 , 41 , 42 , 47 ], but contrarily to others [ 16 , 45 , 48 , 49 ], we did not find prognostic nor predictive value for CDX2 expression in stage II CRC. Yet, this could be, at least in part, due to the size of our series with consequent low number of tumors with loss of CDX2 expression, low number of recurrence events as well as low number of patients treated with chemotherapy.…”

Section: Discussioncontrasting

confidence: 77%

Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

et al. 2021

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Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

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“…No studies showing differential expression of miR-9-5p between peritumoral and tumoral tissues are reported. However, miR-9-5p has been indicated a prognostic biomarker in CRC [31,32].…”

Section: Discussionmentioning

confidence: 99%

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Milanesi

Dobre

Bucuroiu

et al. 2020

Journal of Immunology Research

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microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.

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MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer

Cited by 10 publications

References 41 publications

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

A Novel Prognostic Biomarker Panel for Early-Stage Colon Carcinoma

Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

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