HER2 positivity as a biomarker for poor prognosis and unresponsiveness to anti-EGFR therapy in colorectal cancer

AbstractTumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368–411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin β1 and Talin-1, which facilitated to integrin β1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.

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Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival

Vaccines ◽

10.3390/vaccines9040334 ◽

2021 ◽

Vol 9 (4) ◽

pp. 334

Author(s):

Salman M. Toor ◽

Varun Sasidharan Nair ◽

Reem Saleh ◽

Rowaida Z. Taha ◽

Khaled Murshed ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

T Cell Activation ◽

Cd4 T Cells ◽

Poor Prognosis ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Disease Specific Survival ◽

Unique Gene ◽

Disease Specific

Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.

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High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases

Cancer Biology & Therapy ◽

10.1080/15384047.2020.1803008 ◽

2020 ◽

Vol 21 (9) ◽

pp. 826-831

Author(s):

Reetta Peltonen ◽

Kaisa Ahopelto ◽

Jaana Hagström ◽

Camilla Böckelman ◽

Caj Haglund ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Poor Prognosis

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Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer: The question is still open

Cancer ◽

10.1002/cncr.29598 ◽

2015 ◽

Vol 121 (21) ◽

pp. 3922-3923 ◽

Cited By ~ 2

Author(s):

Soodabeh ShahidSales ◽

Majid Ghayour Mobarhan ◽

Faezeh Ghasemi ◽

Sharareh Gholamin ◽

Amir Avan

Keyword(s):

Colorectal Cancer ◽

Chloride Channel ◽

Poor Prognosis ◽

Low Expression

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Differential expression of DUSP2 in left- and right-sided colon cancer is associated with poor prognosis in colorectal cancer

Oncology Letters ◽

10.3892/ol.2018.7881 ◽

2018 ◽

Author(s):

Wenjie Dong ◽

Na Li ◽

Xiufeng Pei ◽

Xinai Wu

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Differential Expression ◽

Poor Prognosis ◽

Left And Right

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Overexpression of neurone glial-related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer

Cancer Science ◽

10.1111/j.1349-7006.2011.02021.x ◽

2011 ◽

Vol 102 (10) ◽

pp. 1855-1861 ◽

Cited By ~ 7

Author(s):

Jason Y. Chan ◽

Chee W. Ong ◽

Manuel Salto-Tellez

Keyword(s):

Colorectal Cancer ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Poor Prognosis ◽

Cell Adhesion Molecule ◽

Advanced Colorectal Cancer ◽

Independent Predictor ◽

Related Cell

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Human Cytomegalovirus Induced Immune Regulation Is Correlated With Poor Prognosis in Colorectal Cancer Patients

10.21203/rs.3.rs-860887/v1 ◽

2021 ◽

Author(s):

Yangyang Fang ◽

Qiongdan Wang ◽

Kaizhao Huang ◽

Mengyue Zhang ◽

Shunjie Pei ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Function ◽

Human Cytomegalovirus ◽

Poor Prognosis ◽

Hcmv Infection ◽

Information Matrix ◽

Clinical Information ◽

Gene Expression Omnibus ◽

Survival Outcomes ◽

Survival Prognosis

Abstract Available evidence suggests that human cytomegalovirus (HCMV) infection may be implicated in the progression of colorectal cancer (CRC). However, the correlation between HCMV infection and survival outcomes in CRC patients is unclear. Here, we constructed a flow algorithm to identify HCMV sequences based on the RNA-seq data of CRC patients derived from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients' clinical information matrix was used to calculate Euclidean distance to filter out suitable patients not infected with HCMV, combining with the patient's survival outcome to reveal how HCMV infection is involved in CRC progression.HCMV infection is widespread in CRC patients., The prevalence of HCMV infection is ranging from 10% to 36% in 4 independent CRC datasets with infection being concentrated in carcinoma tissue rather than in normal tissue. In addition, HCMV positive patients had a poor survival prognosis, with three of the HCMV genes associated with poor patient survival outcomes, UL82, UL42 and UL117. Most importantly, we suppose that the regulation of immune function by HCMV may be the key to the poor prognosis of CRC patients. We found that HCMV infection was associated with poor prognosis in CRC patients and identified three prognosis associated HCMV genes. The regulation of immune function caused by HCMV infection was the key factor while HCMV positive CRC patients mostly presented a state of immunosuppression. This may provide new ideas for personalized treatment of CRC patients, especially in immunotherapy.

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