Biomarkers of lymph node metastasis in colorectal cancer: update.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.

Pan-cancer analysis of 60S Ribosomal Protein L7-Like 1 (RPL7L1) and validation in liver hepatocellular carcinoma.

BACKGROUND AND AIMS: There is an association between cancer and increased ribosome biogenesis. At present, the RPL7L1 (60S Ribosomal Protein L7-Like 1) were less reported by literature search. Study reports that RPL7L1 is associated with mouse embryonic and skeletal muscle. The study of RPL7L1 on tumors has not been reported. METHODS: Our team downloaded the pan-cancer dataset that is uniformly normalized from the UCSC database (N=19131). Our study examined the relationship between RPL7L1 expression level and clinical prognosis with methylation, anti-tumour immunity, functional states, MSI, TMB, DNSss, LOH and chemotherapeutic responses in 43 cancer types and subtypes. RESULTS AND CONCLUSIONS: RPL7L1 was overexpressed in nine tumor types. Gene mutation, tumor microenvironment and methylation modification of RPL7L1 plays a key role in patient prognosis. And the high expression of RPL7L1 was associated with TMB, MSI, LOH especially LIHC and HNSC. We experimentally verified that genes can promote the proliferation and migration of tumor cells. Our study suggested that RPL7L1 biomarker can be used for treating cancer, detecting it, and predicting its prognosis.

Impacts of pre-existing diabetes mellitus on colorectal cancer in a mice model.

BACKGROUND: Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre-existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression. METHODS: In this study, we investigated the effects of DM on CRC progression in a streptozotocin-induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA-seq. RESULTS: Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM-CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+ T cells, CD8+ T cells and mucosal-associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM. CONCLUSION: For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre-existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.

Over-expression of Nav1.6 channels is associated with lymph node metastases in colorectal cancer.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is a key factor in predicting and determining the prognosis of patients with colorectal cancer (CRC). Sodium channels are highly expressed in a variety of tumors and are closely related to tumor development, metastasis, and invasion. We investigated the relationship between the expressions of different subtypes of Nav channels and lymph node metastasis of CRC. METHODS: Real-time PCR (RT-qPCR) was carried out to measure the expressions of different sodium channel subtypes, chemokine receptors (CCR2, CCR4, CCR7), and lymphocyte infiltration-related biomarkers (CD3e, CD8a, IL-2RA) in CRC tissues from 97 patients. The expressions of Nav1.5 and Nav1.6 in surgically isolated lymph nodes were detected by immunohistochemistry. Correlation analysis between expressions of different genes and lymph node metastasis was performed by two-tailed t test. RESULTS: Nav1.1 and Nav1.6 were highly expressed in CRC tissues and positively correlated with CRC lymph node metastasis. Nav1.6 was also highly expressed in metastatic lymph nodes. Further analysis showed that the high expression of Nav1.6 was closely related to the one of CCR2\CCR4 in tumor lymph node metastasis. CONCLUSIONS: These results suggested that Nav1.6 might be a novel marker for CRC lymph node metastasis.