Circulating Biomarkers of Colorectal Cancer (CRC)—Their Utility in Diagnosis and Prognosis

Mokgautsi

et al. 2021

Cells

Tumor recurrence from cancer stem cells (CSCs) and metastasis often occur post-treatment in colorectal cancer (CRC), leading to chemoresistance and resistance to targeted therapy. MYC is a transcription factor in the nuclei that modulates cell growth and development, and regulates immune response in an antitumor direction by mediating programmed death ligand 1 (PD-L1) and promoting CRC tumor recurrence after adjuvant chemotherapy. However, the molecular mechanism through which c-MYC maintains stemness and confers treatment resistance still remains elusive in CRC. In addition, recent reports demonstrated that CRC solid colon tumors expresses C-X-C motif chemokine ligand 8 (CXCL8). Expression of CXCL8 in CRC was reported to activate the expression of PD-L1 immune checkpoint through c-MYC, this ultimately induces chemoresistance in CRC. Accumulating studies have also demonstrated increased expression of CXCL8, matrix metalloproteinase 7 (MMP7), tissue inhibitor of metalloproteinase 1 (TIMP1), and epithelial-to-mesenchymal transition (EMT) components, in CRC tumors suggesting their potential collaboration to promote EMT and CSCs. TIMP1 is MMP-independent and regulates cell development and apoptosis in various cancer cell types, including CRC. Recent studies showed that TIMP1 cleaves CXCL8 on its chemoattractant, thereby influencing its mechanistic response to therapy. This therefore suggests crosstalk among the c-MYC/CXCL8/TIMP1 oncogenic signatures. In this study, we explored computer simulations through bioinformatics to identify and validate that the MYC/CXCL8/TIMP1 oncogenic signatures are overexpressed in CRC, Moreover, our docking results exhibited putative binding affinities of the above-mentioned oncogenes, with our novel small molecule, RV59, Finally, we demonstrated the anticancer activities of RV59 against NCI human CRC cancer cell lines both as single-dose and dose-dependent treatments, and also demonstrated the MYC/CXCL8/TIMP1 signaling pathway as a potential RV59 drug target.

Section: Introductionmentioning

confidence: 99%

Comprehensive Omics Analysis of a Novel Small-Molecule Inhibitor of Chemoresistant Oncogenic Signatures in Colorectal Cancer Cell with Antitumor Effects

Mokgautsi

et al. 2021

Cells

“…Several potential mechanisms have been hypothesized to explain the associations between elevated CRP levels and poor prognosis of CRC. First, elevated CRP levels may reflect aggressive phenotypes of CRC, such as large tumor size, advanced tumor stage, and the presence of distant and lymph node metastases, which are associated with poor prognosis 22 . Second, although CRP per se is unlikely to directly promote cancer development, the serum concentration of CRP represents the magnitude and nature of inflammation in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Preoperative C‐reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer

Journal of Surgical Oncology

Cai

Zhao

et al. 2022

Background: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. Methods: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the timedependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. Results: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). Conclusion:Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.colorectal cancer, C-reactive protein to prealbumin ratio, disease-free survival, inflammatory index, overall survival | INTRODUCTIONGlobally, colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer death. 1 There have been great improvements in our understanding of its etiology, risk factor, molecular biology, and clinical aspects over the past decades, but it still accounts for nearly 10% of the global cancer burden, with over 1.9 million new diagnoses and 0.9 million deaths in 2020. 2 Radical surgery is the preferred treatment for patients with resectable CRC, but for patients who undergo radical resection, the prognosis is still poor, with 60% of patients surviving for 5 years. 3 Tumor progression, including recurrence and distant metastasis, remains a major concern for patients after surgery.

“…Recent works showed that serum CSF-1 has great value in the diagnosis and progression of colorectal cancer (CRC), making it an independent prognostic factor for the survival of patients with CRC 72 . As mentioned before, increased CSF-1R, CSF-1 and IL-34 expression in primary CRC was associated with a mesenchymal-like subtype and tumor invasion as well as distant metastasis 24 , 72 . Recently, immunotherapy has gradually become the focus of cancer treatment.…”

Section: Expression and Significance Of Csf-1 And Csf-1r In Gastrointestinal Malignant Tumorsmentioning

confidence: 99%

“…2 ). A study investigated the effect of CSF/CSF-R on the progression of colon cancer and pancreatic cancer in a mouse model and the results showed that in the absence of CSF-R, macrophage-related tumor cytotoxicity was amplified, indicating that CSF/CSF-R is an important clinical application target for controlling tumor microenvironment and gastrointestinal tumor progression 72 , 78 .…”

Section: Expression and Significance Of Csf-1 And Csf-1r In Gastrointestinal Malignant Tumorsmentioning

confidence: 99%

Colony Stimulating Factor-1 and its Receptor in Gastrointestinal Malignant Tumors

Tang

2021

J. Cancer

Gastrointestinal malignant tumor is the fourth most common cancer in the world and the second cause of cancer death. Due to the susceptibility to lymphatic metastasis and liver metastasis, the prognosis of advanced tumor patients is still poor till now. With the development of tumor molecular biology, the tumor microenvironment and the cytokines, which are closely related to the proliferation, infiltration and metastasis, have become a research hotspot in life sciences. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, and its receptor CSF-1R are reported to play important roles in regulating tumor-associated macrophages in tumor microenvironment and participating in the occurrence and development in diversities of cancers. Targeted inhibition of the CSF-1/CSF-1R signal axis has broad application prospects in cancer immunotherapy. Here, we reviewed the biological characters of CSF-1/CSF-1R and their relationship with gastrointestinal malignancies.