Risk stratification for advanced proximal colon neoplasm and individualized endoscopic screening for colorectal cancer by a risk-scoring model

Background Healthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention. Methods and findings We assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses’ Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants’ mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population. Conclusions Our study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone.

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Identification of ZNF26 as a Prognostic Biomarker in Colorectal Cancer by an Integrated Bioinformatic Analysis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.671211 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jiaxin Liu ◽

Yimin Li ◽

Yaqi Gan ◽

Qing Xiao ◽

Ruotong Tian ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Cancer Patients ◽

Genetic Risk ◽

Positive Association ◽

Differential Analysis ◽

Risk Genes ◽

Scoring Model ◽

Risk Scoring ◽

Colorectal Cancer Patients

The dysregulation of transcriptional factors (TFs) leads to malignant growth and the development of colorectal cancer (CRC). Herein, we sought to identify the transcription factors relevant to the prognosis of colorectal cancer patients. We found 526 differentially expressed TFs using the TCGA database of colorectal cancer patients (n = 544) for the differential analysis of TFs (n = 1,665) with 210 upregulated genes as well as 316 downregulated genes. Subsequently, GO analysis and KEGG pathway analysis were performed for these differential genes for investigating their pathways and function. At the same time, we established a genetic risk scoring model for predicting the overall survival (OS) by using the mRNA expression levels of these differentially regulated TFs, and defined the CRC into low and high-risk categories which showed significant survival differences. The genetic risk scoring model included four high-risk genes (HSF4, HEYL, SIX2, and ZNF26) and two low-risk genes (ETS2 and SALL1), and validated the OS in two GEO databases (p = 0.0023 for the GSE17536, p = 0.0193 for the GSE29623). To analyze the genetic and epigenetic changes of these six risk-related TFs, a unified bioinformatics analysis was conducted. Among them, ZNF26 is progressive in CRC and its high expression is linked with a poor diagnosis as well. Knockdown of ZNF26 inhibits the proliferative capacity of CRC cells. Moreover, the positive association between ZNF26 and cyclins (CDK2, CCNE2, CDK6, CHEK1) was also identified. Therefore, as a novel biomarker, ZNF26 may be a promising candidate in the diagnosis and prognostic evaluation of colorectal cancer.

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450 Risk Stratification for Lymph Node Metastasis in Early Gastric Cancer and Development of a Predictive Risk-Scoring Model

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2014.02.111 ◽

2014 ◽

Vol 79 (5) ◽

pp. AB144

Author(s):

Masau Sekiguchi ◽

Ichiro ODA ◽

Hirokazu Taniguchi ◽

Seiichiro Abe ◽

Satoru Nonaka ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Early Gastric Cancer ◽

Risk Stratification ◽

Scoring Model ◽

Node Metastasis ◽

Risk Scoring ◽

Predictive Risk

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Risk stratification and predictive risk-scoring model for lymph node metastasis in early gastric cancer

Journal of Gastroenterology ◽

10.1007/s00535-016-1180-6 ◽

2016 ◽

Vol 51 (10) ◽

pp. 961-970 ◽

Cited By ~ 38

Author(s):

Masau Sekiguchi ◽

Ichiro Oda ◽

Hirokazu Taniguchi ◽

Haruhisa Suzuki ◽

Shinji Morita ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Early Gastric Cancer ◽

Risk Stratification ◽

Scoring Model ◽

Node Metastasis ◽

Risk Scoring ◽

Predictive Risk

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A Tale of Two Colons and Two Cancers

Swiss Surgery ◽

10.1024/1023-9332.9.1.3 ◽

2003 ◽

Vol 9 (1) ◽

pp. 3-7 ◽

Cited By ~ 5

Author(s):

Gervaz ◽

Bühler ◽

Scheiwiller ◽

Morel

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Splenic Flexure ◽

Chromosomal Instability ◽

Proximal Colon ◽

Colorectal Carcinogenesis ◽

Physiological Data ◽

Central Hypothesis ◽

Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

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Histopathologic risk stratification of stage IIB colorectal cancer

Surgery Today ◽

10.1007/s00595-016-1456-8 ◽

2016 ◽

Vol 47 (8) ◽

pp. 934-939

Author(s):

Koji Komori ◽

Takashi Kinoshita ◽

Taihei Oshiro ◽

Seiji Ito ◽

Tetsuya Abe ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Stratification

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Anorectal Malformations and the Risk of Colorectal Cancer—Is Early Routine Endoscopic Screening Indicated?

European Journal of Pediatric Surgery ◽

10.1055/s-0040-1718749 ◽

2020 ◽

Author(s):

Anna Svenningsson ◽

Anna Gunnarsdottir ◽

Tomas Wester

Keyword(s):

Colorectal Cancer ◽

Early Adulthood ◽

Anorectal Malformations ◽

Population Based ◽

Observational Period ◽

Endoscopic Screening ◽

Medical Birth Register ◽

National Patient ◽

And Gender

Abstract Introduction Colorectal cancer (CRC) has been reported in early adulthood in patients with anorectal malformation (ARM), and therefore, the need of endoscopic controls has been discussed. The aim of this study was to assess the risk of CRC in patients with ARM. Materials and Methods This was a nationwide population-based study with data from Swedish national health care registers. All patients diagnosed with ARM born in Sweden between 1964 and 1999 were identified in the National Patient Register. The same group was followed up in the Swedish Cancer Register from birth to December 31, 2014, for occurrences of CRC. Five age- and gender-matched individuals randomly selected from the Medical Birth Register served as controls for each ARM patient born between 1973 and 1999. Results A total of 817 patients (474 males) with ARM were included and followed up from birth to the end of observational period. Time of follow-up ranged from 15 to 50 years (mean: 28 years). None of the patients was diagnosed with CRC during the observational period. One case of rectal cancer and one case of sigmoid cancer were detected among the 3,760 controls. Conclusion In our study, the risk of CRC in early adulthood in patients with ARM is low. Our result does not support routine endoscopic follow-up for patients with ARM during the first decade of life.

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A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting

Cancers ◽

10.3390/cancers13112762 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2762

Author(s):

Samantha Di Donato ◽

Alessia Vignoli ◽

Chiara Biagioni ◽

Luca Malorni ◽

Elena Mori ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Stratification ◽

Elderly Patients ◽

Metastatic Colorectal Cancer ◽

Early Stage ◽

Prospective Trial ◽

Proton Nuclear Magnetic Resonance ◽

P Value ◽

Resonance Spectroscopy ◽

Metabolomic Fingerprinting

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

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Serum carcinoembryonic antigen pre‐operative level in colorectal cancer: revisiting risk stratification

ANZ Journal of Surgery ◽

10.1111/ans.16861 ◽

2021 ◽

Author(s):

Cristiana Iacuzzo ◽

Paola Germani ◽

Marina Troian ◽

Tommaso Cipolat Mis ◽

Fabiola Giudici ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Stratification ◽

Carcinoembryonic Antigen ◽

Serum Carcinoembryonic Antigen

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The Relationship between Inflammation Markers (CRP, IL-6, sCD40L) and Colorectal Cancer Stage, Grade, Size and Location

Diagnostics ◽

10.3390/diagnostics11081382 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1382

Author(s):

Olga Martyna Koper-Lenkiewicz ◽

Violetta Dymicka-Piekarska ◽

Anna Justyna Milewska ◽

Justyna Zińczuk ◽

Joanna Kamińska

Keyword(s):

Colorectal Cancer ◽

Linear Regression ◽

Tumor Size ◽

Distal Colon ◽

Proximal Colon ◽

Model Parameters ◽

Grade Group ◽

Who Grade ◽

The Mean ◽

Mean Concentration

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.

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