Unhealthy lifestyle factors and the risk of colorectal cancer: a Mendelian randomization study.

The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12-1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01-1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15-10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.

Advancing mid-rectal cancer surgery: Unveiling the potential of natural orifice specimen extraction surgery in comparison to conventional laparoscopic-assisted resection.

BACKGROUND: Mid-rectal cancer treatment traditionally involves conventional laparoscopic-assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. AIMS: To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long-term prognosis between NOSES and CLAR groups. MATERIALS & METHODS: A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. RESULTS: The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. CONCLUSION: While long-term outcomes (overall survival, disease-free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid-rectal cancer treatment, while maintaining similar long-term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long-term results.

Integrating transcriptomics and machine learning for immunotherapy assessment in colorectal cancer.

Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1-TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Application of the Xi robotic platform for familial adenomatous polyposis with ultra-low rectal cancer: exploration of minimally invasive and refined therapies.

When a familial adenomatous polyposis (FAP) patient's rectal polyp undergoes malignant transformation, the surgeon needs to consider how to balance the quality of surgery with the patient's quality of life. Here, we present a case of robotic surgery in a patient with familial adenomatous polyposis and ultra-low rectal cancer. Fiberoptic colonoscopy found that hundreds of polyp-like bulges were diffusely distributed throughout the colon, and a malignant mass was found at the end of the rectum. The patient underwent total colectomy with abdominoperineal extended radical resection for rectal cancer using the Xi robotic platform. The patient recovered well in the postoperative period. The ileostomy was well used. And the patient was in good health and metastasis free at 9 months postoperatively. We identified total colectomy combined with extended radical rectal resection under the assistance of the da Vinci robot platform is of great benefit to the patient.

The optimal minimum lymph node count for carcinoembryonic antigen elevated colon cancer: a population-based study in the SEER set and External set.

PURPOSE: The aim of this paper was to clarify the optimal minimum number of lymph node for CEA-elevated (≥ 5 ng/ml) colon cancer patients. METHODS: Thirteen thousand two hundred thirty-nine patients from the SEER database and 238 patients from the Second Affiliated Hospital of Harbin Medical University (External set) were identified. For cancer-specific survival (CSS), Kaplan-Meier curves were drawn and data were analyzed using log-rank test. Using X-tile software, the optimal cut-off lymph node count was calculated by the maximal Chi-square value method. Cox regression model was applied to perform survival analysis. RESULTS: In CEA-elevated colon cancer, 18 nodes were defined as the optimal minimum node. The number of lymph node examined (< 12, 12-17 and ≥ 18) was an independent prognosticator in both SEER set (HR12-17 nodes = 1.329, P < 0.001; HR< 12 nodes = 1.985, P < 0.001) and External set (HR12-17 nodes = 1.774, P < 0.032; HR< 12 nodes = 2.741, P < 0.006). Moreover, the revised 18-node standard could identify more positive lymph nodes compared with the 12-node standard in this population. CONCLUSIONS: With the purpose of favorable long-term survival and accurate nodal stage for CEA-elevated colon cancer patients, the 18-node standard could be regarded as an alternative to the 12-node standard advocated by the ASCO and NCCN guidelines.

Gut microbiota display alternative profiles in patients with early-onset colorectal cancer.

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing worldwide. This study aimed to explore whether there is an alternative gut microbiota profile in patients with early-onset colorectal cancer. Methods: A total of 24 patients with EOCRC, 43 patients with late-onset colorectal cancer and 31 young volunteers were included in this study. The diversity of their fecal bacteria was explored using 16S ribosomal RNA gene sequencing. Cluster of ortholog genes (COG) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) were used to detect enrichment pathways among the three groups. Results: Community separations were observed among the three groups. The Shannon index of the EOCRC group was significantly lower than the LOCRC group (P=0.007) and the NC group (P=0.008). Both PCoA analysis (Principal co-ordinates analysis, P=0.001) and NMDS (non-metric multidimensional scaling, stress=0.167, P=0.001) analysis indicated significant difference in beta diversity among the three groups. Fusobacteria, Bacteroidetes, and Clostridia were the most abundant bacteria in the EOCRC group, LOCRC group, and NC group, respectively. The results of COG showed that transcription (P=0.01398), defense mechanisms (P=0.04304), inorganic ion transport and metabolism (P=0.00225) and cell wall/membrane/envelope biogenesis (P=0.02534) were differentially expressed among the three groups. The KEGG modules involved in membrane transport (P=0.00856) and porphyrin and chlorophyll metabolism (P=0.04909) were differentially expressed among the three groups. Conclusion: Early-onset colorectal cancer patients have a different gastrointestinal microbiota derangement compared to late-onset colorectal cancer patients. This dysbiosis can be reflected in the species diversity of the microbiota, the abundance of bacteria, and the abnormal functional predictions.

Long-term oncologic outcomes of natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of rectal cancer: a propensity-score matching study.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. METHODS: From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. RESULTS: From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P < 0.001), lower rate of postoperative complications (5.7% vs 15.5%, P = 0.020), more satisfaction with body image (P = 0.001) and cosmesis (P < 0.001) postoperatively. The NOSES group had a higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between the two groups. CONCLUSION: NOSES could be a safe and reliable technique for radical resection of rectal cancer, with better short-term outcomes than conventional laparoscopy, while long-term survival is not significantly different from that of conventional laparoscopic surgery.

Nomogram to Predict the Risk of Postoperative Anxiety and Depression in Colorectal Cancer Patients.

Purpose: To develop and validate the risk nomogram to predict the likelihood of postoperative anxiety and depression in colorectal cancer (CRC) patients. Methods: A total of 602 CRC patients from the Second Affiliated Hospital of Harbin Medical University were included in the study and divided into development set and validation set with the 2:1 ratio randomly. Logistic regression model was used to determine independent factors contributing to postoperative anxiety and depression, which were subsequently applied to build the nomogram for predicting postoperative anxiety and depression. The performance of the risk nomogram was appraised by the area under the receiver operating curve (AUC), calibration curves and decision curve analyses (DCA). Results: Gender, personal status, income, adjuvant therapy, the Eastern Cooperative Oncology Group Scale (ECOG) score, comorbidity, postoperative complications and stoma status were significant indicators for postoperative anxiety and depression. The AUCs for the development and validation sets were 0.792 and 0.812 for the postoperative anxiety nomogram and 0.805 and 0.825 for the postoperative depression nomogram. Additionally, calibration curves and decision curve analyses also determined the reliable clinical importance of the proposed nomogram. Conclusion: The current study constructed the risk nomogram for postoperative anxiety and depression and could help clinicians determine high-risk patients to some extent.

Exploration of a modified stage for pN0 colon cancer patients.

Exploring a modified stage (mStage) for pN0 colon cancer patients. 39,637 pN0 colon cancer patients were collected from the SEER database (2010-2015) (development cohort) and 455 pN0 colon cancer patients from the Second Affiliated Hospital of Harbin Medical University (2011-2015) (validation cohort). The optimal lymph nodes examined (LNE) stratification for cancer-specific survival (CSS) was obtained by X-tile software in the development cohort. LNE is combined with conventional T stage to form the mStage. The novel N stage was built based on the LNE (N0a: LNE ≥ 26, N0b: LNE = 11-25 and N0c: LNE ≤ 10). The mStage include mStageA (T1N0a, T1N0b, T1N0c and T2N0a), mStageB (T2N0b, T2N0c and T3N0a), mStageC (T3N0b), mStageD (T3N0c, T4aN0a and T4bN0a), mStageE (T4aN0b and T4bN0b) and mStageF (T4aN0c and T4bN0c). Cox regression model showed that mStage was an independent prognostic factor. AUC showed that the predictive accuracy of mStage was better than the conventional T stage for 5-year CSS in the development (0.700 vs. 0.678, P < 0.001) and validation cohort (0.649 vs. 0.603, P = 0.018). The C-index also showed that mStage had a superior model-fitting. Besides, calibration curves for 3-year and 5-year CSS revealed good consistencies between observed and predicted survival rates. For pN0 colon cancer patients, mStage might be superior to conventional T stage in predicting the prognosis.

How Best to Play the Role of Tumor Deposits in Stage III Colon Cancer?

Background: The purpose of this study is to comprehensively evaluate the prognostic role of tumor deposits (TD) in stage III colon cancer. Methods: 24,600 CC patients with III stage colon cancer were collected from the Surveillance, Epidemiology, and End Result (SEER) database and 618 CC patients from the Second Affiliated Hospital of Harbin Medical University. All patients were divided into development, internal, and external validation cohorts. The combination of positive lymph nodes (PLN) and the status or number of TD was defined as modified pN (mpN) and novel pN (npN). The Cox proportional hazard regression model was used to analyze the relationship between cancer-specific survival (CSS) and mpN or npN. CSS stratified by pN, mpN, and npN was analyzed by the Kaplan-Meier curves. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the predictive abilities of the pN, mpN, and npN stages. The validation cohorts were used to validate the results. Results: The Cox proportional hazard regression model showed that mpN and npN were an independent prognostic factor for CSS. AUC showed that the predictive accuracy of mpN was better than that of the pN stage for 5-year CSS in the development (0.621 vs. 0.609, p < 0.001) and internal validation cohorts (0.618 vs. 0.612, p = 0.016) and the npN was also better than the pN stage for 5-year CSS in the development (0.623 vs. 0.609, p < 0.001) and internal validation cohorts (0.620 vs. 0.612, p = 0.001). However, there was no significant difference between the AUCs of mpN and npN. Moreover, the pN stage for 5-year CSS in the external validation cohort is 0.606 vs. 0.563, p = 0.045. Conclusions: In stage III CC, mpN and npN may be superior to the pN stage in assessing prognosis, suggesting that the TD information should be included in the pN stage.

Nomogram for predicting occurrence of synchronous liver metastasis in colorectal cancer: a single-center retrospective study based on pathological factors.

PURPOSE: The purpose of this study was to explore the risk factors for synchronous liver metastasis (LM) of colorectal cancer (CRC) and to construct a nomogram for predicting the occurrence of synchronous LM based on baseline and pathological information. METHODS: The baseline and pathological information of 3190 CRC patients were enrolled in the study from the Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University between 2012 and 2020. All patients were divided into development and validation cohorts with the 1:1 ratio. The characters of LM and none-LM patients in newly diagnosed colorectal cancer were utilized to explore the risk factors for synchronous LM with the univariate and multivariate logistic regression analyses. A predictive nomogram was constructed by using an R tool. In addition, receiver operating characteristic (ROC) curves was calculated to describe the discriminability of the nomogram. A calibration curve was plotted to compare the predicted and observed results of the nomogram. Decision-making curve analysis (DCA) was used to evaluate the clinical effect of nomogram. RESULTS: The nomogram consisted of six features including tumor site, vascular invasion (VI), T stage, N stage, preoperative CEA, and CA-199 level. ROC curves for the LM nomogram indicated good discrimination in the development (AUC = 0.885, 95% CI 0.854-0.916) and validation cohort (AUC = 0.857, 95% CI 0.821-0.893). The calibration curve showed that the prediction results of the nomogram were in good agreement with the actual observation results. Moreover, the DCA curves determined the clinical application value of predictive nomogram. CONCLUSIONS: The pathologic-based nomogram could help clinicians to predict the occurrence of synchronous LM in postoperative CRC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

Natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection for colorectal cancer in elderly patients: a propensity-score matching study.

Whether natural orifice specimen extraction surgery (NOSES) could provide beneficial effects in treating elderly patients is still under debate. The aim of the study was to compare the clinical outcomes of transanal NOSES with conventional laparoscopic-assisted resection (LA) in elderly colorectal cancer (CRC) patients. A retrospective analysis from the Second Affiliated Hospital of Harbin Medical University between 2013 and 2017 was performed. Outcomes related to surgery, body image, quality of life, anal function and long-term survival were compared between the two groups with the propensity-score matching (PSM) method. After PSM, 78 patients were successfully compared. Patients with NOSES had faster gastrointestinal function recovery (P = 0.028), less postoperative complications (P = 0.025), lower pain scores on days 1, 3 and 5 after surgery (P < 0.001). The body image score (P < 0.001) and cosmetic score (P < 0.001) were significantly higher in the NOSES group than the LA group at 1 month after surgery. Patients with NOSES posed better global health status (P < 0.001), role function (P = 0.009), emotional function (P = 0.011) and social function (P = 0.011) at 3 months after surgery. Moreover, NOSES showed non inferiority in anal function 6 months after surgery. No significant difference could be found regarding to overall survival (OS), disease-free survival (DFS), local recurrence (LR) and distant metastasis (DM). In elderly CRC patients, NOSES harbored favorable postoperative outcomes, excellent cosmetic properties and better quality of life. Besides, anal function and long-term outcomes of NOSES can be sure for elderly patients.

Nomogram to Predict the Occurrence and Prognosis of Distant Metastasis in T1N0 Colon Cancer: A SEER Data-Based Study.

PURPOSE: Distant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients. METHODS: Patients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan-Meier curves were generated and analyzed using Log rank tests. RESULTS: A total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879-0.922) and 0.899 (95% CI=0.865-0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744-0.782), 0.794 (95% CI=0.775-0.813), and 0.822 (95% CI=0.803-0.841) for the development cohort, and 0.785 (95% CI=0.754-0.816), 0.748 (95% CI=0.717-0.779) and 0.896 (95% CI=0.865-0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639-0.737) and 0.712 (95% CI=0.681-0.743). CONCLUSION: The population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

Role of Phenotypes of Circulating Tumor Cells in the Diagnosis and Treatment of Colorectal Cancer.

OBJECTIVE: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs' numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity. METHODS: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics. RESULTS: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) >5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs >1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced. CONCLUSION: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.

Genomic Analysis Reveals Heterogeneity Between Lesions in Synchronous Primary Right-Sided and Left-Sided Colon Cancer.

Background: The synchronous primary right-sided and left-sided colon cancer (sRL-CC) is a peculiar subtype of colorectal cancer. However, the genomic landscape of sRL-CC remains elusive. Methods: Twenty-eight paired tumor samples and their corresponding normal mucosa samples from 14 patients were collected from the Second Affiliated Hospital of Harbin Medical University from 2011 to 2018. The clinical-pathological data were obtained, and whole-exome sequencing was performed based on formalin-fixed and paraffin-embedded samples of these patients, and then, comprehensive bioinformatic analyses were conducted. Results: Both the lesions of sRL-CC presented dissimilar histological grade and differentiation. Based on sequencing data, few overlapping SNV signatures, onco-driver gene mutations, and SMGs were identified. Moreover, the paired lesions harbored a different distribution of copy number variants (CNVs) and loss of heterozygosity. The clonal architecture analysis demonstrated the polyclonal origin of sRL-CC and inter-cancerous heterogeneity between two lesions. Conclusion: Our work provides evidence that lesions of sRL-CC share few overlapping mutational signatures and CNVs, and may originate from different clones.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis.

Fibroblast activation protein alpha (FAP) is a marker of cancer-associated fibroblast, which is also expressed in cancer epithelial cells. However, the role of FAP in colorectal cancer (CRC) cells remains to be elucidated. Here we investigate the expression pattern of FAP in CRC tissues and cells to prove that FAP is upregulated in CRC cells. Loss- of and gain-of-function assays identified FAP promotes migration and invasion instead of an effect on cell proliferation. Microarray assays are adopted to identify the different expressed genes after FAP knockdown and gene set enrichment analysis (GSEA) is used to exploit the involved signaling pathway. Our works reveal FAP exerts a function dependent on NF-κB signaling pathway and FAP expression is associated with NF-κB signaling pathway in clinical samples. Our work shows FAP is secreted by CRC cells and soluble FAP could promote metastasis. To investigate the mechanism of FAP influencing the NF-κB signaling pathway, LC/MS is performed to identify the proteins interacting with FAP. We find that FAP binds to ENO1 and activates NF-κB signaling pathway dependent on ENO1. Blocking ENO1 could partially reverse the pro-metastatic effect mediated by FAP. We also provide evidences that both FAP and ENO1 are associated with CRC stages, and high levels of FAP and ENO1 predict a poor survival in CRC patients. In summary, our work could provide a novel mechanism of FAP in CRC cells and a potential strategy for treatment of metastatic CRC.

Application of Field-of-View Optimized and Constrained Undistorted Single Shot (FOCUS) with Intravoxel Incoherent Motion (IVIM) in 3T in Locally Advanced Rectal Cancer.

PURPOSE: To evaluate the efficacy of field-of-view (FOV) optimized and constrained undistorted single shot (FOCUS) with IVIM in 3T MRI in the grading of patients with locally advanced rectal cancer. METHODS: From January 1st to December 31st, 2019, patients with locally advanced rectal cancer were retrieved. FOCUS DWI and FOCUS IVIM were obtained. Apparent diffusion coefficient (ADC) and IVIM parameters including mean true diffusion coefficient (D), pseudodiffusion coefficient associated with blood flow (D∗), and perfusion fraction (f) of the tumor parenchyma and normal rectal wall, as well as the normalized tumor parameters by corresponding normal intestinal wall parameters (ADCNOR, D NOR, D∗NOR, and f NOR), were compared between the well/moderately differentiated and poorly differentiated groups by Student's t-test. The relationship between the above parameters and the histologic grade was analyzed using Spearman's correlation test, with the ROC curve generated. RESULTS: Eighty-eight patients (aged 31 to 77 years old, mean = 56) were included for analysis. D tumor and f tumor were positively correlated with the tumor grade (r = 0.483, p < 0.001 and r = 0.610, p < 0.001, respectively). All the normalized parameters (ADCNOR, D NOR, D∗NOR, and f NOR) were positively correlated with the tumor grade (r = 0.267, p = 0.007; r = 0.564, p = 0.001; r = 0.414, p = 0.005; and r = 0.605, p < 0.001, respectively). The best discriminative parameter was the f tumor value, and the area under the ROC curve was 0.927. With a cut-off value of 22.0%, f tumor had a sensitivity of 88.9% and a specificity of 100%. CONCLUSION: FOCUS IVIM-derived parameters and normalized parameters are useful for predicting the histologic grade in rectal cancer patients.

Comparison of natural orifice specimen extraction surgery and conventional laparoscopic-assisted resection in the treatment effects of low rectal cancer.

Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.