Female Colorectal Cancer Patients Research Articles

Sex differences in health-related quality of life and psychological distress among colorectal cancer patients: a 2-year longitudinal study.

While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up. Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 334) completed questions on HRQoL (EORTC QLQ-C30) and psychological distress (HADS) before initial treatment (baseline), 4 weeks after surgery, and at 1 and 2 years after diagnosis. Also, HRQoL and psychological distress were assessed in a sex- and age-matched reference population. When directly comparing female (N = 126, 38%) and male (N = 208, 62%) CRC patients, female patients reported significantly worse HRQoL, such as more insomnia at baseline, worse physical and role functioning 4 weeks after surgery, more diarrhea at 1 year, and more pain and constipation at 2-year follow-up. However, a comparison with the reference population revealed larger differences between patients and reference in males than in females. For example, at 1- and 2-year follow-up, male patients reported significantly worse cognitive and social functioning, more insomnia, and more anxiety compared with a reference population. Especially male CRC patients reported worse HRQoL and more psychological distress when compared with a reference population. Knowledge of sex-specific differences in HRQoL and psychological distress among CRC patients may help healthcare providers anticipate and appropriately address patients' unique healthcare needs.

Third-generation PacBio sequencing to explore gut bacteria and gender in colorectal cancer

BackgroundGut bacteria have an important influence on colorectal cancer (CRC). The differences of gut bacteria between genders have been the hot spots. ObjectiveTo analyze the relationship between gut bacteria and gender differences in patients with CRC. MethodsA total of 212 patients with CRC and 212 healthy volunteers were recruited. The subjects' fecal samples were obtained, and the fecal microorganisms were analyzed by the third-generation sequencing PacBio. The composition of gut bacteria was analyzed. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the differences in gut bacteria. Pearson coefficient was used to calculate the correlation between differential bacteria. CRC risk prediction models were used to rank the importance of effective differential bacteria. ResultsEscherichia flexneri and Phocaeicola vulgatus were the most frequent bacteria in both male and female CRC patients. Bacteroides, Verrucomicrobia and Akkermansiaceae were highly enriched in male CRC group, while Bacteroidetes, Phocaeicola and Tissierellales were highly enriched in female CRC group. Peptostreptococcus anaerobius and Phocaeicola vulgatus were important CRC related bacteria in males and females, respectively. Peptostreptococcus anaerobius was the most important characteristic bacterium of males (AUC = 0.951), and the sensitivity and specificity of the discovery set were 78.74 % and 93.98 %, respectively. Blautia stercoris was the most important characteristic bacterium of females (AUC = 0.966), and the sensitivity and specificity of the discovery set were 90.63 % and 90.63 %, respectively. ConclusionGut bacteria varied in different genders. Therefore, gender should be considered when gut bacteria are applied in the diagnose and prevention of CRC.

Factors associated with sexual dysfunction in patients with colorectal cancer in Iran: a cross-sectional study

Sexual dysfunction is a prevalent issue among individuals diagnosed with colorectal cancer (CRC), significantly impacting their quality of life. However, limited research has explored the factors associated with sexual dysfunction in CRC patients in Iran. This cross-sectional study aimed to identify the demographic factors that may contribute to sexual dysfunction in this population. A cross-sectional study involving CRC patients was conducted from April 1, 2022, to May 1, 2022, in Tabriz, Iran. Ethical approvals were obtained, and convenience sampling was employed at outpatient chemotherapy centers in five Tabriz hospitals. Validated questionnaires, including participants characteristics form, the Female Sexual Function Index (FSFI) for females and International Index of Erectile Function (IIEF) for males, were utilized. Data were analyzed using IBM SPSS Statistics version 24, employing descriptive statistics and stepwise linear regression to assess association between mentioned factors and sexual function. Among 256 participants, 50.4% were males, 49.6% were females, and 80.5% were married. The predominant age range was 50–60 years. The study findings revealed a high prevalence of sexual dysfunction among both female (Mean ± SD: 10.91 ± 8.67, Min–Max: 3.20–33.00) and male (Mean ± SD: 27.64 ± 16.28, Min–Max: 11–62) CRC patients. Factors such as the presence of a colostomy for FSFI (P < 0.001), type of treatment received for both FSFI and IIEF (P < 0.001), type of housing for both FSFI and IIEF (P < 0.001), occupation for FSFI (P < 0.001), presence of other diseases for FSFI (P = 0.047), and time since the last chemotherapy session for FSFI (P = 0.018), Education for IIEF (P = 0.026), and Age for IIEF (P = 0.002) were identified as significant factors of sexual dysfunction. These demographic factors demonstrated varying effects on sexual function, underscoring the complexity of this issue. The results underscore the significance of addressing sexual health concerns in CRC patients and highlight the necessity for tailored interventions to enhance their overall well-being. Healthcare providers should recognize the influence of demographic factors on sexual function and contemplate integrating sexual health assessments and interventions into the care of CRC patients. Further research is needed to comprehend better the underlying mechanisms and devise effective strategies for managing sexual dysfunction in this population.

Fertility preservation in reproductive-aged female patients with colorectal cancer: a scoping review.

Colorectal cancer (CRC) incidence in adults younger than 50 years is steadily increasing in the USA, and treatment for CRC can impact future fertility. However, fertility decision-making in female patients with CRC can be complex, with fertility preservation (FP) counseling occurring inconsistently. The goal of this scoping review was to assess the literature regarding the frequency and quality of fertility preservation (FP) discussions taking place among oncology clinicians and their reproductive-age female patients with colorectal cancer (CRC) in order to identify existing gaps in care and inform future research, interventions, or potential changes in practice. A comprehensive literature search was conducted using the Ovid Medline, PsycInfo, and Scopus databases in order to identify studies pertaining to FP counseling in reproductive-age female patients with CRC. We used Covidence to screen studies for relevance and to extract data. Findings of interest included rate of fertility and/or FP discussions, patient characteristics associated with fertility discussions, initiators of discussions, rate of referrals to fertility specialists, patient utilization of FP services, and unmet fertility needs. We performed both quantitative and qualitative data synthesis. We identified five studies that met our inclusion criteria, all published between 2007 and 2022. Frequency of fertility counseling discussions was low across studies, with a range of 15 to 52.5% of female patients with CRC receiving counseling. Patient characteristics which may be associated with likelihood of fertility discussion included age, parity, number of children, cancer location and stage, treatment type, and quality of life. The literature suggested that fertility discussions were initiated by clinicians about two-thirds of the time, and medical oncologists were the clinicians most likely to initiate. Studies did capture unmet fertility-related patient needs; participants who did not receive counseling often expressed desire for these discussions and regret that they did not occur. Despite increasing incidence of CRC in patients at younger ages, this scoping review found a dearth of research conducted on young female CRC patients' experiences with fertility counseling and referrals. Notably, the existing research reveals that relatively few of these patients are receiving appropriate counseling. Additional research is needed to clarify current FP counseling practices, patient and clinician perceptions about FP, and ways to improve the quantity and quality of FP counseling in this patient population.

Factors associated with reproductive concerns among young female patients with colorectal cancer: A cross-sectional study.

The aim of this study was to describe the prevalence of reproductive concerns among young female patients with colorectal cancer and explore the associated factors. With the trend of longer survival and younger age at diagnosis of colorectal cancer patients, reproductive concerns have become increasingly prevalent among young female colorectal cancer patients. Cross-sectional design. The study included 150 young female patients with colorectal cancer who completed cancer treatment at 2 hospitals in Guangzhou, China, between November 2020 and December 2021 completed an investigation comprising A general questionnaire, The Reproductive Concerns After Cancer scale, The Family Adaptation and Cohesion Evaluation Scale II and unmet fertility information needs questionnaire. Multivariable linear regression analysis was performed in order to identify factors that influence reproductive concerns. This study was prepared and is reported according to the STROBE checklist. The mean (SD) score on the Reproductive Concerns After Cancer scale was 54.78 ± 8.97. The highest score was for the children's health subscale (3.84 ± .92) and the lowest was for acceptance (2.24 ± .70). Multiple regression analysis showed that patients with fewer children, female children, lower education level (less than undergraduate degree), earlier disease stage, lower family function and higher unmet need for fertility information had more reproductive concerns, which explained 26.9% of the total variation of the model. The patients with fewer children, female children, low cultural degree (less than bachelor), early clinical patients, poorer family function and higher unmet fertility information needs had higher reproductive concerns. These findings can guide the development of interventions to mitigate reproductive concerns, including understand and meet their fertility information needs, improve the level of family function. Survey questionnaires were completed by participants among young female with colorectal cancer in this study.

A propensity score-matched analysis of oncological outcome after systemic therapy for stage IV colorectal cancer: Impact of synchronous ovarian metastases.

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra-ovarian metastases only. Three-year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score-matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3-year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.

Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review.

Asparagine (Asn) and enzymes that catalyze the metabolism of Asn have been linked to the regulation and propagation of colorectal cancer (CRC). Increased Asn and asparagine synthetase (ASNS) expression, both contribute to CRC progression and metastasis. In contradistinction, L-asparaginase (ASNase) which breaks down Asn, exhibits an anti-tumor effect. Metabolic pathways such as KRAS/PI3K/AKT/mTORC1 signaling and high SOX12 expression can positively regulate endogenous Asn production. Conversely, the tumor suppressor, TP53, negatively impacts ASNS, thus limiting Asn synthesis and reducing tumor burden. Asn abundance can be altered by factors extrinsic to the cancer cell such as diet, the microbiome, and therapeutic use of ASNase. Recent studies have shown that sex-related factors can also influence the regulation of Asn, and high Asn production results in poorer prognosis for female CRC patients but not males. In this narrative review, we critically review studies that have examined endogenous and exogenous modulators of Asn bioavailability and summarize the key metabolic networks that regulate Asn metabolism. We also provide new hypotheses regarding sex-related influences on Asn, including the involvement of the sex-steroid hormone estrogen and estrogen receptors. Further, we hypothesize that sex-specific factors that influence Asn metabolism can influence clinical outcomes in CRC patients.

Ovarian metastases in young women with colorectal cancer: a retrospective multicenter cohort study.

Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19months. This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.

Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients.

We reported that high estrogen receptor beta (ERβ) expression is independently associated with better prognosis in female colorectal cancer (CRC) patients. However, estrogen receptor alpha (ERα) is expressed at very low levels in normal colon mucosa, and its prognostic role in CRC has not been explored. Herein, we investigated the combined role of ERα and ERβ expression in the prognosis of female patients with CRC, which, to the best of our knowledge, is the first study to investigate this topic. A total number of 306 primary CRCs were immunostained for ERα and ERβ expression. A Cox regression model was used to evaluate overall survival (OS) and disease-free survival (DFS). The combined expression of high ERβ + negative ERα correlates with longer OS (HR = 0.23; 95% CI: 0.11–0.45, P <0.0001) and DFS (HR = 0.10; 95% CI: 0.03–0.26, P < 0.0001) and a more favorable tumor outcome, as well as significantly higher expression of antitumorigenic proteins than combined expression of low ERβ + positive ERα. Importantly, we found that low ERβ expression was associated with local recurrence of CRC, whereas ERα expression was correlated with liver metastasis. Overall, our results show that the combined high ERβ + negative ERα expression correlated with a better prognosis for CRC patients. Our results suggest that the combined expression of ERα and ERβ could be used as a predictive combination marker for CRC patients, especially for predicting DFS.

Deep learning analysis of the adipose tissue and the prediction of prognosis in colorectal cancer.

139 Background: Colorectal cancer (CRC) is the third most common type of cancer and has a poor prognosis and high recurrence rate. Research has shown that the lipid microenvironment surrounding tumors is closely associated with the occurrence, development, and metastasis of CRC. Recently, advances in artificial intelligence have greatly improved the accuracy of models for CRC prognosis and survival analysis. Methods: According to pathological images from the National Center for Tumor diseases(NCT), the University Medical Center Mannheim(UMM) database and the ImageNet data set, a model called VGG19 was pre-trained. A deep convolutional neural network(CNN), VGG19CRC, was trained by the migration learning method. According to the VGG19CRC model, adipose tissue scores were calculated for TCGA-CRC hematoxylin and eosin(H&amp;E) images and images from patients at Zhujiang Hospital of Southern Medical University and First People’s Hospital of Chenzhou. Kaplan-Meier(KM) analysis was used to compare the overall survival(OS) of patients. The XCell and MCP-Counter algorithms were used to evaluate the immune cell scores of the patients. Gene set enrichment analysis(GSEA) and single-sample GSEA(ssGSEA) were used to analyze upregulated and downregulated pathways. Results: In TCGA-CRC, patients with high-adipocytes(high-ADI) CRC had significantly shorter OS times than those with low-ADI CRC. In a validation queue from Zhujiang Hospital of Southern Medical University(Local-CRC1), patients with high-ADI had worse OS than CRC patients with low-ADI. In another validation queue from First People's Hospital of Chenzhou(Local-CRC2), patients with low-ADI CRC had significantly longer OS than patients with high-ADI CRC. In subgroup analysis, ADI could be used as a prognostic marker for patients with colon adenocarcinoma(COAD) and rectum adenocarcinoma(READ), as well as male and female CRC patients. Among these subgroups, patients with lower ADI also had significantly improved OS. Compared with the low-ADI group, high-ADI patients had significantly decreased CD8+ T cells, T cells,and monocytes in the tumor immune microenvironment(TIME), while M2 macrophages were significantly increased. According to the GSEA and ssGSEA analyses, pathways mediating anti-tumor immunity were significantly downregulated in the high-ADI group, while some oncogenic signaling pathways were significantly upregulated. Conclusions: We developed a deep convolution network to segment various tissues from pathological H&amp;E images of CRC and automatically quantify ADI. This allowed us to further analyze and predict the survival of CRC patients according to information from their segmented pathological tissue images, such as tissue components and the tumor microenvironment. Furthermore, we found that ADI may also predict OS in CRC patients and among the subgroups.

The Influence of Self Esteem and Sexual Communication on Sexual Satisfaction of Colorectal Cancer Women with Ostomy

Purpose: The purpose of this study was to identify the influence of self-esteem and sexual communication on sexual satisfaction among female colorectal cancer patients with ostomy.Methods: A cross-sectional descriptive study was conducted using self-reported online questionnaires. The participants were 85 women with colorectal cancer who had undergone ostomy formation surgery. Data were analyzed using descriptive statistics, the t-test, analysis of variance, the Scheffé test, correlation coefficients, and hierarchical multiple regression with SPSS version 26.0.Results: The mean sexual satisfaction score was 2.79±0.73 (range, 0~5). There was no significant relationship between self-esteem and sexual satisfaction. Sexual communication had a significant correlation with sexual satisfaction (r=.83, p&lt;.001) and was a strong predictor of sexual satisfaction (β=.83, p&lt;.001).Conclusion: The findings of this study indicate that colorectal cancer patients with ostomy experience low sexual satisfaction and that sexual communication is a meaningful factor for sexual satisfaction. Accordingly, nurses need to factor in sexual issues when caring for patients, and should encourage both patients and their partners to participate in education related to sexual health. It will also be helpful to inform patients about the importance of sexual communication with their partners as a sustainable intervention.

Women are predisposed to early dose-limiting toxicities during adjuvant CAPOX for colorectal cancer.

Oxaliplatin-based adjuvant chemotherapy was demonstrated to be beneficial for stage III or high-risk stage II colorectal cancer (CRC). Moreover, a recent international collaborative trial suggested 3-months CAPOX as an alternative regimen for low-risk stage III colorectal cancer (CRC) patients. Thus, it is important to clarify the frequency and predictive markers of dose-limiting toxicities (DLTs) developed within the short-course CAPOX cycles. We investigated CRC patients who underwent radical surgery and adjuvant CAPOX therapy at our hospital between December 2010 and February 2021. Patients who received initially reduced doses of CAPOX and those who had early recurrence were excluded. We reviewed the age, sex, comorbidities, physical, laboratory and oncological data and other perioperative factors. The associations between these variables and early DLTs within four cycles of CAPOX were examined by multivariate analyses using logistic regression models. Among 168 patients (96 men, mean age: 58.3years), 120 (71%) developed early DLTs. Patients with early DLTs were predominantly women and sarcopenic and habitualalcohol consumers. On multivariate analyses, only the female sex was an independent predictive factor for early DLTs (odds ratio: 2.61, P=.027). Women were prone to early DLTs during adjuvant CAPOX in the current study. Doctors should be aware of the sex difference in the incidence of early DLTs, adjust the CAPOX dosage and provide supportive care for female CRC patients.

Ovarian metastases from colorectal cancer in young women: a systematic review of the literature.

In female colorectal cancer patients, a mean proportion of synchronous and/or metachronous ovarian metastases of 3.4% was described. Previous literature showed that young or premenopausal women (≤ 55years of age) may be more frequently affected. Once ovarian metastases are diagnosed, the prognosis of the patient is generally dismal, with 5-year survival varying from 12 to 27%. The present study is aimed at determining the proportion of young or premenopausal women diagnosed with colorectal cancer who presented with or developed ovarian metastases by reviewing the current literature on this topic. This review was performed by querying MEDLINE and EMBASE databases using a combination of terms: "colorectal neoplasms, colorectal cancer, ovarian neoplasms, Krukenberg tumor, young adult, young age, premenopause." Studies that indicated ovarian metastases, either synchronous or metachronous (or a combination of the two), in young women were retrieved and analyzed. The review identified 14 studies encompassing 3379 young or premenopausal female colorectal cancer patients. In this selected group of patients, a mean proportion of ovarian metastases of 4.6% [95% CI: 4.0;5.4] was found. This review showed that approximately one in twenty young female colorectal cancer patients will present with or develop ovarian metastases. Since outcome of this specific oncological pathology is often dismal, this finding is clinically relevant. It demonstrates the need to develop strategies to lower the incidence of ovarian metastases with adequate treatment and counseling of these patients.

Clinicopathological Association of Autophagy Related 5 Protein with Prognosis of Colorectal Cancer.

Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients.

The effect of mutation status, pathological features and tumor location on prognosis ın patients with colorectal cancer.

Colorectal cancer is the most common malignancy of the gastrointestinal tract. It is the third most common tumor in both genders and the second reason of cancer-related deaths. In recent years, tumor location has gained importance as a prognostic indicator. In this study, we aimed to analyze if there was a prognostic effect of tumor location, the pathological features, and the mutation status of patients on survival. Two-hundred and ten colorectal cancer patients aged 18 years and older were included into the study. One-hundred and forty-two patients had left-sided tumor and 68 patients had right-sided tumor. Patients who had other malignancies rather than squamous cell skin cancer and in situ cervical cancer were excluded. All statistical tests were carried out using two-sided process, and a p≤0.05 was considered statistically significant. There were 140 men and 70 women in the study. The median age of the patients was 62 years old. There was no statistically significant difference according to tumor location and survival of patients. The overall survival of patients with right-sided tumors was 60.5 months and 47.2 months for left-sided tumors. Disease-free survival of patients was 63.7 months for right-sided tumors and 46 months for left-sided ones. Perineural invasion, grade and stage were crucial prognostic parameters. Disease-free survival was longer for female colorectal cancer patients. According to our study, survival of patients was similar regardless of tumor location. This can be explained by the different sequencing of treatment strategies and divergent population genetics.

The Validity of a New Edition of Classification for Ovarian Metastasis from Colorectal Cancer.

Objectives: In the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC), ovarian metastasis is classified as distant metastasis. We assessed the significance of resection of ovarian metastases and the validity of this 9th edition of JCCRC for ovarian metastases from colorectal cancer (CRC). Methods: We retrospectively analyzed the clinicopathological factors and overall survival of 17 patients with ovarian metastases from CRC who underwent resection and 110 female CRC patients with Stage IV (M1a) disease. Results: The patients with only ovarian metastases who underwent resection had a longer median survival time than patients with both ovarian and peritoneal metastases who underwent resection (45.4 months vs. 9.3 months, P = 0.029). The 5-year overall survival of the patients with only ovarian metastases who underwent R0 resection was as long as that of the female Stage IV (M1a) CRC patients after R0 resection (50% vs. 48%, P = 0.334). Conclusions: We found that, after resection, patients with only ovarian metastases had significantly better prognoses than patients with ovarian and peritoneal metastases. R0 resection of ovarian metastasis indicated as good prognosis as R0 resection of metastasis to one distant organ without ovaries. So the 9th edition of JCCRC, which classifies ovarian metastasis from CRC as distant metastasis, is appropriate.

Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila.

Developmental studies revealed fundamental principles on how organ size and function is achieved, but less is known about organ adaptation to new physiological demands. In fruit flies, juvenile hormone (JH) induces intestinal stem cell (ISC) driven absorptive epithelial expansion balancing energy uptake with increased energy demands of pregnancy. Here, we show 20-Hydroxy-Ecdysone (20HE)-signaling controlling organ homeostasis with physiological and pathological implications. Upon mating, 20HE titer in ovaries and hemolymph are increased and act on nearby midgut progenitors inducing Ecdysone-induced-protein-75B (Eip75B). Strikingly, the PPARγ-homologue Eip75B drives ISC daughter cells towards absorptive enterocyte lineage ensuring epithelial growth. To our knowledge, this is the first time a systemic hormone is shown to direct local stem cell fate decisions. Given the protective, but mechanistically unclear role of steroid hormones in female colorectal cancer patients, our findings suggest a tumor-suppressive role for steroidal signaling by promoting postmitotic fate when local signaling is deteriorated.

Tumour-suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model.

Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti-tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane-associated β-catenin, cysteinyl leukotriene receptor 2 (CysLT2 R), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which have anti-tumour effects, but lower levels of nuclear β-catenin, cysteinyl leukotriene receptor 1 (CysLT1 R), and cyclooxygenase-2 (COX-2), which have tumour-promoting effects. These interesting findings were further supported by two different publicly available CRC mRNA datasets that showed a significant positive correlation between ERβ expression and 15-PGDH and CysLT2 R expression and a negative correlation between ERβ expression and β-catenin, CysLT1 R, and COX-2 expression. We next evaluated ERβ expression in three different colon cancer mouse models; ERβ expression was negatively correlated with tumourigenesis. Furthermore, treatment with the ERβ-agonist ERB-041 reduced CysLT1 R, active β-catenin, and COX-2 levels but increased phospho-β-catenin, CysLT2 R, and 15-PGDH levels in HCT-116, Caco-2, and SW-480 colon cancer cells compared to vehicle-treated cells. Interestingly, ERB-041-treated cells showed significantly decreased migration, survival, and colonosphere formation and increased apoptotic activity, as indicated by increased CASPASE-3 and apoptotic blebs. Finally, patients with low ERβ expression had significantly more distant metastasis at the time of diagnosis than patients with high ERβ expression. Therefore, we studied the effects of ERB-041-treated colon cancer cells in a zebrafish xenograft model. We found significantly less distant metastasis of ERB-041-treated cells compared to vehicle-treated cells. These results further support ERβ's anti-tumour role in CRC and the possible use of its agonist in CRC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Incidence, risk factors, treatment, and survival of ovarian metastases of colorectal origin: a Dutch population-based study.

The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5months, adjusted HR 0.44 [0.33-0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5months, ranging from 3.1months in patients without treatment to 34.1months in patients undergoing CRS-HIPEC.

Effect of metformin on the mortality of colorectal cancer patients with T2DM: meta-analysis of sex differences.

To evaluate the effect of metformin as a treatment for the mortality of colorectal cancer (CRC) patients with type 2 diabetes mellitus (T2DM). We searched Medline, PubMed, EMBASE, Clinical Trials.gov (http://www.clinicaltrials.gov), and the Cochrane Collaboration Library from inception to November 2019. To analyze the relationship between metformin and the overall mortality, specific mortality, and sex differences in CRC patients with T2DM, hazard ratios (HRs) with 95% confidence intervals (CIs) were used. Egger's test and Begg's test were used to assess publication bias. We included 8 cohort studies in our meta-analysis. CRC patients with T2DM treated with metformin had a lower overall mortality than CRC patients with T2DM who did not receive metformin (HR = 0.80, 95% CI 0.67-0.95). There was no significant difference in CRC-specific mortality between CRC patients with T2DM who used metformin and those who did not (HR = 0.84, 95% CI 0.65-1.08). However, females had a lower CRC-specific mortality among CRC patients with T2DM than males (HR = 0.63, 95% CI 0.41-0.97). Metformin reduced the overall mortality of CRC patients with T2DM. Moreover, female CRC patients with T2DM using metformin had lower CRC-specific mortality than male CRC patients with T2DM.