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Background: Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients., Materials and Methods: A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables., Results: The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P =0.009), with a threshold ( N =16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not., Conclusions: Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Colorectal cancer (CRC) is the most common and fatal tumor in the gastrointestinal system. Its incidence and mortality rate have increased in recent years. Hypoxia, a persistent physiological tumor feature, plays a vital role in CRC tumorigenesis, metastasis, and tumor microenvironment (TME). Therefore, we constructed a hypoxia-related gene (HRG) nomogram to predict overall survival (OS) and explored the role of HRGs in the CRC TME. The Cancer Genome Atlas (TCGA) dataset was used as the training set, and two Gene Expression Omnibus datasets (GSE39582 and GSE103479) were used as the testing sets. HRGs were identified using the Gene Set Enrichment Analysis (GSEA) database. An HRG prognostic model was constructed in the training set using the least absolute shrinkage and selection operator regression algorithm and validated in the testing sets. Then, we analyzed tumor-infiltrating cells (TICs) using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Furthermore, single-cell next-generation RNA sequencing (RNA-seq) was used to investigate HRG expression in different TICs in the GSE139555 dataset. Finally, reverse transcription polymerase chain reactions (RT-PCR) were used to validate HRG mRNA expression in ten pairs of CRC normal and cancer tissue samples. A six HRG prognostic signature was constructed, with a superior OS prediction ability in CRC patients (area under the receiver operating characteristic curve (AUC) at one year: 0.693, AUC at three years: 0.712, and AUC at five years: 0.780). GSEA enrichment analysis identified six pathways enriched in the high-risk group. The TIC analysis indicated that the high-risk group had lower T-cell expression and higher neutrophil expression than the low-risk group. Furthermore, immune-related genes had an inseparable relationship with the HRG prognostic signature. Based on single-cell RNA-seq data, we found elevated hexokinase 1 (HK1) and glucose-6-phosphate isomerase (GPI) gene expression in natural killer (NK) and CD8 + T cells. RT-PCR in ten CRC normal-tumor tissue pairs showed that expression of the signature's six HRGs varied differently in cancerous and paracancerous tissues. The constructed HRG signature successfully predicted the OS of whole-stage CRC patients. In addition, we showed that the signature's six HRGs were closely associated with the TME in CRC, where hypoxia inhibits the antitumor function of T cells., (© 2023. The Author(s).)

The occurrence and development of tumors cannot be separated from the influence of differentiation at different stages and levels. Our study found that E-cadherin was significantly increased in cell model induced by sodium butyrate and cell density, while METTL3, METTL16 and WTAP were decreased during the differentiation of cells. In the clinicopathological tissues, E-cadherin was low expressed in poorly differentiated tumor tissues and above three regulators were highly expressed in poorly differentiated tissues. At the levels of clinicopathological differentiation, tissue differentiation and cell differentiation, the result indicated that the poor prognosis of colorectal cancer (CRC) may be closely related to high expression of total m6A level and high expression of METTL3, METTL16 and WTAP., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)