Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms

Unveiling Prognosis Cancer-Associated Thromboembolism Biomarkers and Their Related Polymorphisms: Exploring Their Involvement With Immune Circulating Cells and Therapeutic Reversibility

This study aims to assess biomarkers and their related polymorphisms in the context of cancer-associated thromboembolism, with a particular focus on their interaction with the immune system. The roles of immune checkpoints, inflammatory and angiogenesis factors, as well as circulating immune cells will be elucidated. Additionally, our investigation extends to the exploration of long non-coding RNAs (LncRNAs) and genes associated with the coagulation vascular system. Initially, these aspects will be evaluated in the context of colorectal cancer, with the intention to expand our research to other solid tumors.

The identification of these biomarkers and genetic factors holds the potential to revolutionize therapeutic approaches for patients with cancer-associated thromboembolism, shedding light on their chemotherapy resistance. The effectiveness of combining immunotherapy with targeted inhibitors like Palbociclib and anticoagulants such as Rivaroxaban, among other potential interventions, will be assessed.

This study aims to make significant contributions to the understanding of these critical aspects, ultimately leading to the development of more effective treatment strategies for cancer patients.

Cancer, especially solid tumors, remains a significant global health challenge despite ongoing advancements in risk factor identification and targeted therapies. Among the various complexities of cancer treatment, the relationship between cancer and thromboembolism, characterized by arterial and venous thrombosis, has attracted attention due to its significant impact on patient outcomes.

Cancer cells activate the coagulation system, leading to prothrombotic disorders in the vascular wall and promoting tumor progression. Patients with cancer, particularly those undergoing systemic chemotherapy, face an increased risk of thromboembolism due to abnormal blood clotting mechanisms.

Recent research has emphasized the importance of identifying novel biomarkers for risk assessment, prognosis determination, and treatment selection in cancer. Among these biomarkers, long non-coding RNAs (LncRNAs) and those of the vascular coagulation system have emerged as pivotal players in cancer development and progression. However, their role as prognostic and predictive biomarkers for cancer risk and treatment response remains relatively unexplored.

Understanding the complex interplay between cancer, immune responses, and thromboembolism is crucial. Immunological subsets, including central immune effector T cells (CD8+, CD25+), NK cells, and macrophages, have been linked to cancer prognosis. Furthermore, therapies that modulate the immune system, such as immunotherapy and cell-based therapies, hold promise for improving cancer treatment outcomes.

Most notably, these therapies exhibit immunomodulatory effects, triggering immunogenic cell death and preventing immunosuppression. However, their efficacy may be compromised in cases of cancer associated with clotting abnormalities within the circulatory system. Progenitor cells, including stem cells and endothelial progenitor cells (EPCs), are emerging as potential players in cancer therapy, offering new avenues for research.

Among the innovative approaches is the assessment of circulating immune and endothelial progenitor cells (termed "CIEs"), which may play significant roles in the mechanisms underlying cancer-associated thromboembolism. Understanding the relationship between these cells, inflammatory and angiogenic factors, immune checkpoint, and cancer progression could pave the way for improved cancer risk assessment and treatment strategies.

This study seeks to contribute to our understanding of the intricate connections between LncRNA, coagulation-related biomarkers, thromboembolism, immune responses, and cancer, using solid tumors as a representative example. By shedding light on these complex interactions, this study aims to identify potential biomarkers that can guide risk assessment and treatment decisions, ultimately improving the management of cancer patients.

Inclusion Criteria:

• Individuals of white ethnicity.
• Age between > 18
• Both males and females.
• Diagnosis of selected cancer type (e.g., colorectal cancer).
• Cancer stage 0/I/II without metastasis or lymph node dissemination at the time of enrollment.
• No previous cancer therapy (radiotherapy, chemotherapy, or immunotherapy) received before study enrollment.
• Unrelated patients.

Exclusion Criteria:

• Cancer stage III/IV.
• History of hematological cancer types or previous cancers, recurrent or relapse.
• Diagnosis of inflammatory bowel diseases.
• Pre-existing cardiovascular diseases or coronary artery diseases.
• Confirmed treated or untreated autoimmune diseases.
• Metabolic disorders, diabetes, or hypertension.
• Neurological diseases.
• Evidence of cardiac, renal, bone, or cerebral damage.
• Presence of more than one type of malignancies.
• Active infections or myositis.
• Familial polyposis.
• Alcohol or smoking habits.
• Colon-affecting food allergies.
• Body mass index (BMI) >30.
• Significant weight loss within the last 2 years.
• History of abdominal surgeries.
• Pregnancy.
• Related patients.