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Gastroenterology Jul 2023Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic...
BACKGROUND & AIMS
Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs.
METHODS
We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis.
RESULTS
We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC.
CONCLUSIONS
We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.
Topics: Humans; Proteome; Proteomics; Colorectal Neoplasms; Colonic Polyps; Adenoma; Neoplasms, Second Primary; Colonoscopy; Risk Factors
PubMed: 36966943
DOI: 10.1053/j.gastro.2023.03.208 -
BMC Women's Health Mar 2023Polycystic ovary syndrome (PCOS) is characterized by anovulation, insufficient progesterone, hyperandrogenism, and insulin resistance. These factors can disrupt the...
Polycystic ovary syndrome is associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women: a retrospective study in a tertiary teaching hospital.
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by anovulation, insufficient progesterone, hyperandrogenism, and insulin resistance. These factors can disrupt the endometrium of PCOS patients and can lead to chronic low-grade inflammation in the endometrium, endometrial hyperplasia, or even endometrial cancer.
OBJECTIVE
The aim of this study was to investigate the prevalence of premalignant and malignant endometrial polyps in premenopausal women and to further explore whether PCOS is associated with premalignant and malignant changes in endometrial polyps.
METHODS
This study was conducted by retrieving the medical data of 4236 premenopausal women who underwent hysteroscopic polypectomies between January 2015 and December 2021. Demographic and clinical data regarding age, height, weight, parity, hormone replacement therapy, oral contraceptives, abnormal uterine bleeding, hypertension, diabetes mellitus, PCOS, number of polyps, and size of polyps were collected, and their associations with premalignant and malignant changes in endometrial polyps were analysed.
RESULT
Among the endometrial polyps removed by hysteroscopic polypectomy in premenopausal women, the prevalence of premalignant and malignant polyps was 2.15%, which comprised hyperplasia with atypia at 1.13% and endometrial carcinoma at 1.02%. PCOS was associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women after adjustment for potential confounding factors.
CONCLUSION
PCOS is associated with a higher risk of premalignant and malignant endometrial polyps in premenopausal women. Therefore, it is important to evaluate the endometrium in PCOS patients with ultrasonography or hysteroscopy, and active management involving hysteroscopic polypectomy should be offered to PCOS patients diagnosed with endometrial polyps regardless of symptoms.
Topics: Pregnancy; Humans; Female; Retrospective Studies; Polycystic Ovary Syndrome; Uterine Neoplasms; Uterine Diseases; Endometrial Neoplasms; Precancerous Conditions; Endometrium; Hysteroscopy; Hospitals, Teaching; Polyps
PubMed: 36964546
DOI: 10.1186/s12905-023-02269-4 -
Frontiers in Oncology 2023Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal...
Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal carcinogenesis is elevated cyclooxygenase-2. Prostaglandin E2 (PGE) over-production is frequently equated with cyclooxygenase-2 gene over-expression. PGE can be assessed by measuring the level of prostaglandin's main metabolite, PGE-M, in urine. Colorectal adenoma is a precancerous lesion that can lead to colorectal cancer. We conducted research to evaluate the association between urinary levels of the PGE-M and the risk of colorectal adenomas. In a western Chinese population, we identified 152 cases of adenoma and 152 controls patients without polyps. Adenoma cases were categorized into control, low-risk and high-risk groups. There was no significant change in PGE-M levels, between the control group and the low-risk adenoma group. In the high-risk group, the PGE-M levels were 23% higher than the control group. When compared to people with the lowest urine PGE-M levels (first quartile), people with greater urinary PGE-M levels had a higher chance of developing high-risk colorectal adenomas, with an adjusted odds ratio (95% CI) of 1.65 (0.76-3.57) in the fourth quartile group, (p= 0.013). We conclude urinary PGE-M is associated with the risk of developing high-risk adenomas. Urinary PGE-M level may be used as a non-invasive indicator for estimating cancer risk.
PubMed: 36923425
DOI: 10.3389/fonc.2023.1068469 -
Journal of Inflammation Research 2023This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological...
PURPOSE
This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological features and influence on the immune profile in colorectal cancer (CRC).
PATIENTS AND METHODS
The Cancer Genome Atlas Colorectal Adenocarcinoma cohorts were used. We also analyzed 131 clinical samples of colon lesions, including precancerous lesions (hyperplastic polyps, low-grade dysplasia, and high-grade dysplasia) and CRC tissues. We conducted immunohistochemical (IHC) assays and multiple IHC (mIHC) of CD4+, Foxp3+ tumor-infiltrating lymphocytes (TILs), and PD-1/PD-L1 immune checkpoints in precancerous lesions and CRC samples from our patient subsets to determine changes and correlations in ICOS and ICOSLG expression during progression through the adenoma-carcinoma pathway.
RESULTS
High expression of ICOS and ICOSLG was a significant factor in CRC in multiple analyses and was positively correlated with CD4+/Foxp3+ TIL density and PD-1/PD-L1 expression, which increased with the sequential progression of lesions from precancerous tissues to carcinoma. Multivariable logistic regression analysis suggested that the location and expression level of ICOS/ICOSLG may be involved in precancerous-carcinoma progression. The co-expression status of PD-1 and ICOS/ ICOSLG could stratify patients with colorectal lesions into three groups of low, moderate, and high risk of progression. According to this classification and mIHC assays, we found a strong correlation between increased PD-1+ICOS+ or PD-1+ICOSLG+ co-expression and CRC, which might be deemed an independent factor in carcinogenesis.
CONCLUSION
Increased ICOS/ICOSLG expression may be associated with the progressive formation of Foxp3+ TILs in the immune microenvironment and may further promote the development of the abnormal cytology of colorectal lesions from precancerous neoplasia to CRC. Our findings support the interpretation that enhanced co-expression of PD-1+ICOS+ or PD-1+ICOSLG+ contributes to the immune-active microenvironment of the colorectal adenoma-carcinoma sequence.
PubMed: 36915615
DOI: 10.2147/JIR.S401123 -
Cancers Mar 2023Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and... (Review)
Review
Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota's pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.
PubMed: 36900392
DOI: 10.3390/cancers15051602 -
Biomedical Optics Express Feb 2023Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-cancerous polyps....
Colonoscopy remains the gold standard investigation for colorectal cancer screening as it offers the opportunity to both detect and resect pre-cancerous polyps. Computer-aided polyp characterisation can determine which polyps need polypectomy and recent deep learning-based approaches have shown promising results as clinical decision support tools. Yet polyp appearance during a procedure can vary, making automatic predictions unstable. In this paper, we investigate the use of spatio-temporal information to improve the performance of lesions classification as adenoma or non-adenoma. Two methods are implemented showing an increase in performance and robustness during extensive experiments both on internal and openly available benchmark datasets.
PubMed: 36874484
DOI: 10.1364/BOE.473446 -
Digestive Diseases and Sciences Jun 2023Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients.
METHODS
Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models.
RESULTS
Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]).
CONCLUSION
Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.
Topics: Colonic Polyps; Irritable Bowel Syndrome; Colorectal Neoplasms; Incidence; Humans
PubMed: 36871131
DOI: 10.1007/s10620-023-07885-6 -
Genome Medicine Mar 2023The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely...
BACKGROUND
The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely investigated. Here, we aimed to systematically identify specific susceptible genetic variants for EOCRC.
METHODS
Two parallel GWASs were conducted in 17,789 CRC cases (including 1490 EOCRC cases) and 19,951 healthy controls. A polygenic risk score (PRS) model was built based on identified EOCRC-specific susceptibility variants by using the UK Biobank cohort. We also interpreted the potential biological mechanisms of the prioritized risk variant.
RESULTS
We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model. Compared to the individuals in the low genetic risk group, the individuals in the high genetic risk group have increased EOCRC risk, and these results were replicated in the UKB cohort with a 1.63-fold risk (95% CI: 1.32-2.02, P = 7.67×10). The addition of the identified EOCRC risk loci significantly increased the prediction accuracy of the PRS model, compared to the PRS model derived from the previous GWAS-identified loci. Mechanistically, we also elucidated that rs12794623 may contribute to the early stage of CRC carcinogenesis via allele-specific regulating the expression of POLA2.
CONCLUSIONS
These findings will broaden the understanding of the etiology of EOCRC and may facilitate the early screening and individualized prevention.
Topics: Humans; Middle Aged; Alleles; Carcinogenesis; Risk Factors; Chromatin Assembly and Disassembly; Colorectal Neoplasms
PubMed: 36869385
DOI: 10.1186/s13073-023-01163-w -
Frontiers in Medicine 2023Several studies have shown that colorectal adenomas are the most important precancerous lesions. The colonoscopic identification of groups with the high risk of...
BACKGROUND
Several studies have shown that colorectal adenomas are the most important precancerous lesions. The colonoscopic identification of groups with the high risk of malignant colorectal adenomas remains a controversial issue for clinicians.
AIMS
To evaluate the basic characteristics of colorectal adenomas with malignancy risk using high-grade dysplasia (HGD) as an alternative marker for malignant transformation.
METHODS
Data from Shanghai General Hospital between January 2017 and December 2021 were retrospectively analyzed. The primary outcome was the incidence of HGD in adenomas, which was used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the HGD rate in adenomas were analyzed in relation to adenoma-related factors.
RESULTS
A total of 9,646 patients identified with polyps during 57,445 screening colonoscopies were included in the study. Patients with flat polyps, sessile polyps, and pedunculated polyps represented 27.3% ( = 2,638), 42.7% ( = 4,114), and 30.0% ( = 2,894) of the total number, respectively. HGD was found in 2.41% ( = 97), 0.92% ( = 24), and 3.51% ( = 98) of sessile adenomas, flat adenomas, and pedunculated adenomas, respectively ( < 0.001). Multivariable logistic regression showed that polyp size ( < 0.001) but not shape ( > 0.8), was an independent predictor of HGD. Contrast to the diameter ≤1 cm, the OR value for diameters 1-2, 2-3, and >3 cm was 13.9, 49.3, and 161.6, respectively. The HGD incidence also increased in multiple adenomas (>3 vs. >1, ORs 1.582) and distal adenomas (distal vs. proximal adenomas, OR 2.252). Adenoma morphology (pedunculated vs. flat) was statistically significant in univariate analysis but not when size was included in the multivariate analysis. Besides, the incidence of HGD was also significantly higher in older patients (>64 vs. <50 years old, OR = 2.129). Sex ( = 0.681) was not statistically significant. All these associations were statistically significant ( < 0.05).
CONCLUSION
The malignant potential of polyps is mostly affected by their size but not by their shape. In addition, distal location, multiple adenomas, and advanced age were also correlated with malignant transformation.
PubMed: 36844218
DOI: 10.3389/fmed.2023.1106272 -
Medical Image Computing and... Sep 2022Colonoscopy is a gold standard procedure but is highly operator-dependent. Automated polyp segmentation, a precancerous precursor, can minimize missed rates and timely...
Colonoscopy is a gold standard procedure but is highly operator-dependent. Automated polyp segmentation, a precancerous precursor, can minimize missed rates and timely treatment of colon cancer at an early stage. Even though there are deep learning methods developed for this task, variability in polyp size can impact model training, thereby limiting it to the size attribute of the majority of samples in the training dataset that may provide sub-optimal results to differently sized polyps. In this work, we exploit and features in the form of text attention during training. We introduce an auxiliary classification task to weight the text-based embedding that allows network to learn additional feature representations that can distinctly adapt to differently sized polyps and can adapt to cases with multiple polyps. Our experimental results demonstrate that these added text embeddings improve the overall performance of the model compared to state-of-the-art segmentation methods. We explore four different datasets and provide insights for size-specific improvements. Our proposed (TGANet) can generalize well to variable-sized polyps in different datasets. Codes are available at https://github.com/nikhilroxtomar/TGANet.
PubMed: 36780239
DOI: 10.1007/978-3-031-16437-8_15