Dataset Information

L1CAM is involved in lymph node metastasis via ERK1/2 signaling in colorectal cancer.

ABSTRACT: L1-cell adhesion molecule (L1CAM, L1) belongs to the immunoglobulin superfamily and was originally found to play a role in nerve cells. Recently, the expression and prognostic value of L1 has been established in several cancers, including colorectal cancer (CRC). However, its association with lymph node metastasis in CRC and the mechanisms underlying its effects remain unclear. In this study, we evaluated the L1 transcript levels in CRC (n=12) and normal intestinal tissues (n=15) by qRT-PCR. Western blotting was used to evaluate L1 and pERK1/2 expression levels. Immunohistochemistry was performed to evaluate the relationship between L1 and pERK1/2 in CRC tissues with different levels of differentiation. The mRNA expression levels in CRC tissues were significantly higher compared to normal intestinal tissues. Western blotting demonstrated that both L1 and pERK1/2 levels were higher in CRC than in normal tissues. Immunohistochemistry confirmed that L1 and pERK1/2 levels in adenomas with lymph node metastasis were significantly higher than in poorly and well-differentiated adenomas, indicating that L1 and pERK1/2 levels correlated with CRC lymph node metastasis. In conclusion, L1 and pERK1/2 were significantly up-regulated in CRC tissues and lymph node metastasis may occur via the L1CAM-mediated ERK pathway in CRC.

SUBMITTER: Fang QX

PROVIDER: S-EPMC7137048 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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L1CAM is involved in lymph node metastasis via ERK1/2 signaling in colorectal cancer.

Fang Qing-Xia QX Zheng Xiao-Chun XC Zhao Hua-Jun HJ

American journal of translational research 20200315 3

L1-cell adhesion molecule (L1CAM, L1) belongs to the immunoglobulin superfamily and was originally found to play a role in nerve cells. Recently, the expression and prognostic value of L1 has been established in several cancers, including colorectal cancer (CRC). However, its association with lymph node metastasis in CRC and the mechanisms underlying its effects remain unclear. In this study, we evaluated the L1 transcript levels in CRC (n=12) and normal intestinal tissues (n=15) by qRT-PCR. Wes ...[more]

PMID: 32269716

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Project description:Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4. The SNPs in solute carrier family 28 member 3 (SLC28A3), breast cancer 1 (BRCA1), ribonucleotide reductase regulators subunit M2 (RRM2), PMS1 homolog 2 (PMS2), cytidine deaminase (CDA), epoxide hydrolase 1 (EPHX1), heterogenous ribonucleoprotein particle-associated with lethal yellow (RALY), Siglec-3 (CD33), B cell lymphoma 10 (BCL10), ETS variant 1 (ETV1), macrophage stimulating 1 receptor 1 (MST1R), lysine methyltransferase 2B (KMT2B), B cell lymphoma 2 (BCL2), U6 small nuclear RNA-associated Sm-like protein 3 (LSM3), thyroid transcription factor 1 (TTF1) and mitogen-activated protein 3 kinase 1 (MAP3K1) were significantly associated with lymphatic metastasis (P<0.05). EGF and NFKB1 were both observed to be significantly downregulated in the lymph node metastases group (P<0.05). Although no association between CNVs and lymph node metastases in patients with colorectal cancer was observed in the present study, SNPs in SLC28A3, BRCA1, RRM2, PMS2, CDA, EPHX1, RALY, CD33, BCL10, ETV1, MST1R, KMT2B, BCL2, LSM3, TTF1 and MAP3K1 were significantly associated with colorectal cancer. Downregulation of EGF and NFKB1 was also identified to be associated with lymph node metastases in colorectal cancer. The findings of the current study provide a scientific basis for the clinical inspection of lymphatic metastasis and prognosis prediction, intervention and guidance therapy for patients with colorectal cancer.

Project description:AimsRecent studies have shown that the microenvironment can include cancer cells and cancer-associated fibroblasts (CAFs), and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyse the expression patterns of cancer cell- and CAF-related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM).Methods and resultsQuantitative analysis was conducted for Ki-67, p53, β-catenin and matrix metalloproteinase-7 (MMP7) to assess cancer cell markers. In addition, we examined CAF markers, including smooth muscle alpha-actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP-1), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast-associated protein 1 (FAP-1), zinc finger E-box binding homeobox 1 (ZEB1) and TWIST-related protein 1 (TWIST1). In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell- and CAF- related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterised by high expression of Ki-67, p53, FAP-1, platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and TWIST1, was correlated with LNM (P < 0.01). Next, we examined the associations of individual biomarkers with LNM. Multivariate analysis showed that high expression levels of Ki-67 and FAP-1 were significantly associated with LNM (P < 0.05).ConclusionsOur findings showed that expression patterns of cancer cell- and CAF-related proteins may allow for stratification of patients into risk categories for LNM in SiCRC. In addition, Ki-67- and FAP-1-expressing microenvironmental cells might be helpful for identification of correlations with LNM in SiCRC.

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L1CAM is involved in lymph node metastasis via ERK1/2 signaling in colorectal cancer.

Publications

L1CAM is involved in lymph node metastasis via ERK1/2 signaling in colorectal cancer.

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