Significant association of MCP1 rs1024611 and CCR2 rs1799864 polymorphisms with colorectal cancer and liver metastases susceptibility and aggressiveness: A case-control study.

BACKGROUND: The MCP-1/CCR2 axis is one of the major chemokine signaling pathways that play a crucial role in the tumor microenvironment and has been involved in triggering various tumor progression mechanisms, such as increasing the immunosuppressive cells recruitment and promoting tumor cell proliferation and invasiveness. AIM: The current study investigated the association of MCP1 (rs1024611) and CCR2 (rs1799864) genes variants with the risk as well as prognosis of colorectal cancer (CRC) and colorectal liver metastases (CRLM). SUBJECTS AND METHODS: A retrospective cohort study involved 408 patients (284 CRC and 124 CRLM), and 284 healthy control was conducted. Genotyping of selected polymorphisms was performed by PCR-RFLP assays and confirmed by microchip and capillary electrophoresis. RESULTS: The results highlighted a positive association between MCP1 rs1024611 (non-AA) and CCR2 rs1799864 (GA) genotypes with increased CRC and CRLM risk. Correlation between SNPs and clinicopathological characteristics revealed a positive association between MCP1 rs1024611 and CCR2 rs1799864 (dominant model) and CRC poor prognosis features. Kaplan-Meier survival analysis revealed a significant association between MCP1 rs1024611 non-AA carriers and decreased survival rate. Neoadjuvant treatment showed an improvement in CRC and CRLM survival rates among carriers of MCP1 and CCR2 wild-type genotype. FOLFIRI chemotherapy exhibits reduced survival rates for patients who carried mutated genotypes of MCP1 and CCR2 polymorphisms. CONCLUSION: Considering our results, we suggest That both MCP1 and CCR2 polymorphisms may constitute independent factors for CRC and CRLM occurrence and can be helpful targets for an efficient therapeutic approach.

Obesity and cancer: focus on leptin.

Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In addition, obesity has been associated with a poor prognosis, an increased risk of metastasis and mortality, and resistance to anti-cancer therapies. The pathophysiological mechanisms underlying the obesity-cancer connection have not yet been fully elucidated. However, this connection could result, at least in part, from the action of adipokines, whose levels are increased in obesity. Among these adipokines, evidence suggests leptin's critical role in linking obesity to cancer. In this review, we first summarize the current state of the literature regarding the implication of leptin in tumorigenic processes. Next, we focus on the effects of leptin on the anti-tumor immune response. Then, we discuss the influence of leptin on the efficiency of antineoplastic treatments and the development of tumor resistance. Finally, we highlight the use of leptin as a potential target for the prevention and treatment of cancer.

Leptin Promotes Prostate Cancer Proliferation and Migration by Stimulating STAT3 Pathway.

To better understand the link between obesity and prostate cancer (PC) aggressiveness, we investigate the role of leptin, an obesity associated adipokine, and its receptor (Ob-R) in PC cells migration. The migration assay (Wound-healing) was used to study the leptin impact on DU-145 and PC3 cells lines. STAT3 activation was performed by Western Blot. E-cadherin expression was studied using fluorescence microscopy and Ob-R expression in PC and benign prostatic Hyperplasia (BPH) biopsies was assessed by RT-PCR. In this study we demonstrate that high dose of leptin promotes PC cells migration and EMT transition via the stimulation of STAT3 pathway. In addition, we report that although Ob-R mRNA is expressed by ADK and BPH resections biopsies, significant higher levels were observed for ADK patients. Finally, we found a positive association between Ob-R mRNA expression and worse PC prognosis. A better understanding of the molecular processes of leptin signaling is crucial for identifying appropriate approaches for treatment of obesity-related PC patients.