• Geographic disparities
• Maternal and child health services
• Spatial accessibility
• Spatiotemporal trends
• Two-child policies

• Humans
• China
• Health Services Accessibility/statistics & numerical data
• Female
• Pregnancy
• Healthcare Disparities/trends
• Healthcare Disparities/statistics & numerical data
• Maternal-Child Health Services/trends
• Maternal-Child Health Services/statistics & numerical data
• Family Planning Policy/trends
• Geographic Information Systems
• Spatio-Temporal Analysis
• Child
• Infant, Newborn
• Child, Preschool

• 2SFCA
• Gravity models
• Healthcare
• Kernel density
• Methodological review
• Potential spatial access
• Spatial access measurement

• Humans
• Health Services Accessibility
• Catchment Area, Health

• Leibniz-ScienceCampus "SOEP RegioHub" (Bielefeld University, SOEP/DIW Berlin, Leibniz Association)
• Open Access Publication Fund of Bielefeld University and the Deutsche Forschungsgemeinschaft (DFG)
• Universität Bielefeld (3146)

Several genes, important for development, are reduced or silenced in adulthood, and their abnormal expression has been related to the occurrence and development of malignant tumors. Human sine oculis homeobox homolog (SIX) proteins belong to the homeobox family and play important roles in the development of different organs. Importantly, SIXs are predicted to have chromatin-binding and DNA-binding transcription factor activity with reported roles in cancers. However, a comprehensive analysis of SIXs in colorectal cancers (CRCs) has not been performed.

To explore the expression pattern of six SIX proteins in CRCs and their relationship with the clinicopathological parameters of CRC patients as well as investigate the potential utilization of SIXs as novel prognostic indicators in CRCs.

The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas. Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs. To analyze the potential signaling pathways with SIX family involvement, LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes. Subsequently, immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues, and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray. The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using the χ² test and Fisher’s exact probability to verify the results of the database analysis.

The RNA levels of SIX1-4 and SIX6 were relatively low in normal human tissues, while SIX5 was highly expressed at both the RNA and protein levels. However, the protein level of SIX4 was found to be elevated in various malignancies. In CRC tissues, SIX1, SIX2 and SIX4 were elevated in cancer tissues compared with adjacent normal tissue. Among all SIXs, a high level of SIX4 was found to be associated with poor overall and disease-free survival in patients with CRC. For different clinicopathological parameters, increased SIX4 expression was positively correlated with advanced CRC. The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways.

The current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC. Among different SIXs, SIX4 plays an oncogenic role in CRC to promote the development of malignancy. In CRC, SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival, suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.

• Sine oculis homeobox homolog
• Colorectal cancer
• Development
• Treatment
• Expression
• Prognostic indicator

• Cancer care markets
• Cancer service areas (CSAs)
• Multiscale
• Spatial network community detection
• Spatially constrained Leiden (ScLeiden) method

Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers (CRC). Human six-transmembrane epithelial antigen of the prostate (STEAP) proteins have been recognized and utilized as promising targets for cell- and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.

To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.

The expression level of STEAPs in CRC was evaluated using various open-resource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immune-related biomarkers, such as immune infiltration. Immunohistochemical (IHC) experiments were subsequently performed to verify the database conclusions.

The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However, STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.

Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.

• Six-transmembrane epithelial antigen of the prostate
• Colorectal cancer
• Immunotherapy
• Target
• Survival

• the National Natural Science Foundation of China
• the Natural Science Foundation of Guangdong Province
• the Special Grant for Key Area Programs of Guangdong Department of Education
• the Science and Technology Special Project of Guangdong Province
• “Dengfeng Project” for the Construction of High-level Hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding

Currently, rural residents in the United States (US) experience a greater cancer burden for tobacco-related cancers and cancers that can be prevented by screening. We aim to characterize geographic determinants of colorectal cancer (CRC) incidence in Louisiana due to rural residence and other known geographic risk factors, area socioeconomic status (SES), and cultural region (Acadian or French-speaking).

Primary colorectal cancer diagnosed among adults 30 years and older in 2008–2017 were obtained from the Louisiana Tumor Registry. Population and social and economic data were obtained from US Census American Community Survey. Rural areas were defined using US Department of Agriculture 2010 rural–urban commuting area codes. Estimates of relative risk (RR) were obtained from multilevel binomial regression models of incidence.

The study population was 16.1% rural, 18.4% low SES, and 17.9% Acadian. Risk of CRC was greater among rural white residents (RR Women: 1.09(1.02–1.16), RR Men: 1.11(1.04–1.18)). Low SES was associated with increased CRC for all demographic groups, with excess risk ranging from 8% in Black men (RR: 1.08(1.01–1.16)) to 16% in white men (RR: 1.16(1.08–1.24)). Increased risk in the Acadian region was greatest for Black men (RR: 1.21(1.10–1.33)) and women (RR: 1.21(1.09–1.33)). Rural–urban disparities in CRC were no longer significant after controlling for SES and Acadian region.

SES remains a significant determinant of CRC disparities in Louisiana and may contribute to observed rural–urban disparities in the state. While the intersectionality of CRC risk factors is complex, we have confirmed a robust regional disparity for the Acadian region of Louisiana.

The online version contains supplementary material available at 10.1007/s10552-021-01546-7.

• Colorectal cancer
• Geographic disparities
• Rural
• Socioeconomic status

• Adult
• Colorectal Neoplasms/diagnosis
• Female
• Humans
• Louisiana/epidemiology
• Male
• Rural Population
• Social Class
• Socioeconomic Factors
• United States
• Urban Population

• P20 CA233374 NCI NIH HHS
• P20CA233374 NCI NIH HHS
• National Cancer Institute

Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear.

To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.

Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ² test or Fisher’s exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.

Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ² = 3.957, P < 0.05) and D-LAC (χ² = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.

MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

• Colorectal cancer
• Mucin 2
• Mucin
• Expression
• Intestinal mucosal barrier
• Prognosis

• Biomarkers, Tumor
• Colorectal Neoplasms
• Humans
• Intestinal Mucosa
• Lymphatic Metastasis
• Mucin-1
• Mucin-2
• Prognosis