Early T Stage Is Associated With Poor Prognosis in Patients With Metastatic Liver Colorectal Cancer

Recurrence is the main reason of treatment failure of redical resected colorectal cancer (CRC). Although some factors including staging and differentiation have been proven to useful for recurrence evaluation, prognosis of certain patients does not conform to this evaluation approach. Circulating tumor cells (CTC) have been found to have prognostic value in CRC, and previous studies on CTC have primarily focused on their numbers. CTC are functionally heterogeneous cell populations, and different CTC subgroups may have different functions and clinical values. In our previous study, we discovered that elevated expression of the transient receptor potential channel TRPC5 was associated with a significantly poor prognosis in CRC. In this study, we collected peripheral blood from CTC-positive CRC patients, identified the TRPC5 protein expression on CTC (CTC-TRPC5), and analyzed the relationship between CTC-TRPC5 expression levels and the prognosis. The results showed that CTC-TRPC5 level is significantly related to the T stage and differentiation of tumors. High level of CTC-TRPC5 is more common in a high T stage as well as poorly differentiated tumors and is significantly associated with shorter disease free survival (DFS). The median DFS of CRC patients with high and low CTC-TRPC5 level was 17.1 and 22.0 months, respectively (p < 0.05). This study revealed a clinically significant CTC subgroup of CRC, providing a new indicator for clinical evaluation of CRC prognosis.

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High Expression of LTBP2 Contributes to Poor Prognosis in Patients with Colorectal Cancer

SSRN Electronic Journal ◽

10.2139/ssrn.3244026 ◽

2018 ◽

Author(s):

Ying Huang ◽

Guihua Wang ◽

Chunmei Zhao ◽

Rong Geng ◽

Shu Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

High Expression

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MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly

Cell Death and Differentiation ◽

10.1038/s41418-021-00813-z ◽

2021 ◽

Author(s):

Yan Zhong ◽

Ting Long ◽

Chuan-Sha Gu ◽

Jing-Yi Tang ◽

Ling-Fang Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Focal Adhesion ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Integrin Β1 ◽

Independent Manner ◽

Interacting Protein ◽

Tumour Metastasis ◽

Elevated Expression ◽

Dependent Polarization

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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Complications Following Irinotecan-Loaded Microsphere Chemoembolization of Colorectal Metastatic Liver Lesions Associated with Hepatic-Artery Branch Temporary Stasis

Current Oncology ◽

10.3390/curroncol28030211 ◽

2021 ◽

Vol 28 (3) ◽

pp. 2296-2307

Author(s):

Marcin Szemitko ◽

Elzbieta Golubinska-Szemitko ◽

Jerzy Sienko ◽

Aleksander Falkowski

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Liver Metastases ◽

Hepatic Artery ◽

Liver Lesions ◽

Apparent Lack ◽

Neoplastic Lesion ◽

Hepatic Artery Branch ◽

Artery Branch ◽

Metastatic Liver

Chemoembolization with irinotecan-loaded microspheres has proven effective in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC). Most researchers recommend slowly administering the embolizate at the level of the lobar arteries, without obtaining visible stasis. However, there are reports of a relationship between postoperative embolizate retention in metastatic lesions and the response to treatment. To retain residual embolizate throughout the entire neoplastic lesion requires a temporary flow stop (stasis) within all supply vessels, which may cause temporary stasis in subsegmental or even segmental vessels. Objective: To assess the risk of complications and post-embolization syndrome severity following chemoembolization of CRC metastatic liver lesions with microspheres loaded with Irinotecan, with regard to hepatic-artery branch level of temporary stasis. Patients and methods: The study included 52 patients (29 female, 23 male) with liver metastases from CRC, who underwent 202 chemoembolization treatments (mean: 3.88 per patient) with microspheres loaded with 100 mg irinotecan. Postembolization syndrome (PES) severity and complication occurrence were assessed with regard to the hepatic-artery branch level of temporary stasis. Adverse events were assessed according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. Results: Median survival from the start of chemoembolization was 13 months. From 202 chemoembolization sessions, 15 (7.4%) significant complications were found. The study found a significant relationship between the branch level of temporary stasis and the presence of complications (p < 0.001), with the highest number of complications observed with temporary stasis in segmental vessels. PES was diagnosed after 103 (51%) chemoembolization treatments. A significant association was found between PES severity and the branch level of temporary stasis (p < 0.001). Conclusions: The branch level of temporary stasis affected the severity of post-embolization syndrome. A significant association was found between the branch level of temporary stasis obtained in chemoembolization procedures and the presence of complications. The apparent lack of change in numbers of complications when stasis was applied at tumor supply vessels or subsegmental arteries may indicate the safe use of temporary stasis in some cases where colorectal cancer metastases are treated. Further research is needed to determine the most effective chemoembolization technique.

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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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