CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup

Aasebø, Kristine; Dragomir, Anca; Sundström, Magnus; Mezheyeuski, Artur; Edqvist, Per‐Henrik; Eide, Geir Egil; Pontén, Fredrik; Pfeiffer, Per; Glimelius, Bengt; Sørbye, Halfdan

doi:10.3389/fonc.2020.00008

Cited by 43 publications

(40 citation statements)

References 34 publications

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“…CDX2 was identified as a negative biomarker in 14 cancer types ( Figure 3C). Loss of CDX2 has been reported in colorectal (CRC) tumors that are microsatellite unstable (Aasebø et al, 2020) or PD-L1 positive (Inaguma et al, 2017). These observations are in agreement with the negative association that we identified and suggest a potential role of CDX2 as a biomarker of ICB therapy.…”

Section: Intracellular Network As Biomarkers Of Immune Responsesupporting

confidence: 91%

Predictive systems biomarkers of response to immune checkpoint inhibitors

Lapuente-Santana

Hilbers

et al. 2021

Preprint

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Cancer cells can leverage several cell-intrinsic and -extrinsic mechanisms to escape immune system recognition. The inherent complexity of the tumor microenvironment, with its multicellular and dynamic nature, poses great challenges for the extraction of biomarkers of immune response and immunotherapy efficacy. Here, we use RNA-seq data combined with different sources of prior-knowledge to derive system-based signatures of the tumor microenvironment, quantifying immune-cell composition and intra- and inter-cellular communications. We applied multi-task learning to these signatures to predict different hallmarks of immune responses and derive cancer-type-specific models based on interpretable systems biomarkers. By applying our models to independent RNA-seq data from cancer patients treated with PD-1 inhibitors, we demonstrated that our method to Estimate Systems Immune Response (EaSIeR) accurately predicts therapeutic outcome. We anticipate that EaSIeR will be a valuable tool to provide a holistic description of immune responses in complex and dynamic systems such as tumors using available RNA-seq data.

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Section: Intracellular Network As Biomarkers Of Immune Responsesupporting

confidence: 91%

Predictive systems biomarkers of response to immune checkpoint inhibitors

Lapuente-Santana

Hilbers

et al. 2021

Preprint

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“…CDX2 is a transcription factor and a specific marker of differentiation of intestine, which could be used to identified tumors originating from intestine (36). Aasebo et al reported that CDX2 expression, which accounts for 53% of patients with BRAF mutation in their study, was associated with much better prognosis (34). Our study also demonstrated that loss of CDX2 expression indicated worse survival in patients with BRAF V600E mutation (p = 0.016).…”

Section: Discussionsupporting

confidence: 63%

“…Prognosis of patients with BRAF V600E mutation could be related to MMR/MSI status, or some genetic events occurring in pathogenesis of CRC (29,30,33). Recently, it was reported that CDX2 might play a significant role in prognosis of CRC (34,35). CDX2 is a transcription factor and a specific marker of differentiation of intestine, which could be used to identified tumors originating from intestine (36).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic Features and Prognosis of BRAF Mutated Colorectal Cancer Patients

Guan

Qiu

et al. 2020

Front. Oncol.

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Background:BRAFV600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC.Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC. Patients were classified according to BRAF status as BRAFV600E mutation and non-V600E mutations. Difference of characteristics and survival between the two groups was analyzed.Results: There was no significant difference in gender, family history, location of primary tumor, metastatic sites between patients with BRAF-V600E mutation and non-V600E mutations. Patients with V600E mutation were younger than those with non-V600E mutations (p = 0.002). Patients with BRAFV600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024). Lack of CDX2 expression was associated with worse prognosis (mOS: 9.4 m vs. not reached, respectively, p = 0.016). Status of V600E mutation did not affect the mPFS and ORR of first-line or second-line treatment.Conclusion:BRAFV600E mutation defines a distinct subgroup of CRC with worse prognosis. Lack of CDX2 expression is associated with poor OS. Status of V600E mutation did not affect the mPFS of first-line or second-line treatment.

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“…CDX2 loss was associated with BRAF mutation, and poor differentiation. 14 On the other hand, Baba et al analyzed 621 colorectal cancers, CDX2 loss was detected in 29% tumors and associated with female gender, but not with BRAF. 15 The weakness was that this case did not get genetically tested right away.…”

Section: Discussionmentioning

confidence: 99%

A Case Report: Cutaneous Metastasis of Advanced Rectal Cancer with BRAF Mutation

Zhou

Tang

Wang

et al. 2021

OTT

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Cutaneous metastasis of rectal cancer is rare and typically indicates widespread disease and poor prognosis. We report an exceedingly rare case of BRAF-mutated MSS rectal cancer with metastasis to the skin. A 53-year-old woman presented with stage IV unresectable adenocarcinoma of the rectum and received chemotherapy and molecularly targeted agents. Six months later she developed a focal skin nodule in the left groin. During treatment with four cycles of FOLFIRI plus bevacizumab, the skin nodules gradually increased in size, involving the skin of the left thigh. A portion of the rash was bleeding and painful. The biopsy specimen was consistent with a mucinous adenocarcinoma of rectal origin and expressed reduced CDX-2. Palliative treatment with FOLFIRI plus cetuximab and vemurafenib was initiated. The cutaneous nodules decreased in size but were not stable. The patient had severe electrolyte disturbances and depression and opted for palliative care.

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CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup

Cited by 43 publications

References 34 publications

Predictive systems biomarkers of response to immune checkpoint inhibitors

Predictive systems biomarkers of response to immune checkpoint inhibitors

Clinicopathologic Features and Prognosis of BRAF Mutated Colorectal Cancer Patients

A Case Report: Cutaneous Metastasis of Advanced Rectal Cancer with BRAF Mutation

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