Identification of KRAS mutation-associated gut microbiota in colorectal cancer and construction of predictive machine learning model.

Gut microbiota has demonstrated an increasingly important role in the onset and development of colorectal cancer (CRC). Nonetheless, the association between gut microbiota and KRAS mutation in CRC remains enigmatic. We conducted 16S rRNA sequencing on stool samples from 94 CRC patients and employed the linear discriminant analysis effect size algorithm to identify distinct gut microbiota between KRAS mutant and KRAS wild-type CRC patients. Transcriptome sequencing data from nine CRC patients were transformed into a matrix of immune infiltrating cells, which was then utilized to explore KRAS mutation-associated biological functions, including Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways. Subsequently, we analyzed the correlations among these KRAS mutation-associated gut microbiota, host immunity, and KRAS mutation-associated biological functions. At last, we developed a predictive random forest (RF) machine learning model to predict the KRAS mutation status in CRC patients, based on the gut microbiota associated with KRAS mutation. We identified a total of 26 differential gut microbiota between both groups. Intriguingly, a significant positive correlation was observed between Bifidobacterium spp. and mast cells, as well as between Bifidobacterium longum and chemokine receptor CX3CR1. Additionally, we also observed a notable negative correlation between Bifidobacterium and GOMF:proteasome binding. The RF model constructed using the KRAS mutation-associated gut microbiota demonstrated qualified efficacy in predicting the KRAS phenotype in CRC. Our study ascertained the presence of 26 KRAS mutation-associated gut microbiota in CRC and speculated that Bifidobacterium may exert an essential role in preventing CRC progression, which appeared to correlate with the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:proteasome binding. Furthermore, the RF model constructed on the basis of KRAS mutation-associated gut microbiota exhibited substantial potential in predicting KRAS mutation status in CRC patients.IMPORTANCEGut microbiota has emerged as an essential player in the onset and development of colorectal cancer (CRC). However, the relationship between gut microbiota and KRAS mutation in CRC remains elusive. Our study not only identified a total of 26 gut microbiota associated with KRAS mutation in CRC but also unveiled their significant correlations with tumor-infiltrating immune cells, immune-related genes, and biological pathways (Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways). We speculated that Bifidobacterium may play a crucial role in impeding CRC progression, potentially linked to the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:Proteasome binding. Furthermore, based on the KRAS mutation-associated gut microbiota, the RF model exhibited promising potential in the prediction of KRAS mutation status for CRC patients. Overall, the findings of our study offered fresh insights into microbiological research and clinical prediction of KRAS mutation status for CRC patients.

Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients.

BACKGROUND: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. METHOD: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. RESULT: There was no significant difference in α diversity and ß diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. CONCLUSIONS: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.

Association of the pathomics-collagen signature with lymph node metastasis in colorectal cancer: a retrospective multicenter study.

BACKGROUND: Lymph node metastasis (LNM) is a prognostic biomarker and affects therapeutic selection in colorectal cancer (CRC). Current evaluation methods are not adequate for estimating LNM in CRC. H&E images contain much pathological information, and collagen also affects the biological behavior of tumor cells. Hence, the objective of the study is to investigate whether a fully quantitative pathomics-collagen signature (PCS) in the tumor microenvironment can be used to predict LNM. METHODS: Patients with histologically confirmed stage I-III CRC who underwent radical surgery were included in the training cohort (n = 329), the internal validation cohort (n = 329), and the external validation cohort (n = 315). Fully quantitative pathomics features and collagen features were extracted from digital H&E images and multiphoton images of specimens, respectively. LASSO regression was utilized to develop the PCS. Then, a PCS-nomogram was constructed incorporating the PCS and clinicopathological predictors for estimating LNM in the training cohort. The performance of the PCS-nomogram was evaluated via calibration, discrimination, and clinical usefulness. Furthermore, the PCS-nomogram was tested in internal and external validation cohorts. RESULTS: By LASSO regression, the PCS was developed based on 11 pathomics and 9 collagen features. A significant association was found between the PCS and LNM in the three cohorts (P < 0.001). Then, the PCS-nomogram based on PCS, preoperative CEA level, lymphadenectasis on CT, venous emboli and/or lymphatic invasion and/or perineural invasion (VELIPI), and pT stage achieved AUROCs of 0.939, 0.895, and 0.893 in the three cohorts. The calibration curves identified good agreement between the nomogram-predicted and actual outcomes. Decision curve analysis indicated that the PCS-nomogram was clinically useful. Moreover, the PCS was still an independent predictor of LNM at station Nos. 1, 2, and 3. The PCS nomogram displayed AUROCs of 0.849-0.939 for the training cohort, 0.837-0.902 for the internal validation cohort, and 0.851-0.895 for the external validation cohorts in the three nodal stations. CONCLUSIONS: This study proposed that PCS integrating pathomics and collagen features was significantly associated with LNM, and the PCS-nomogram has the potential to be a useful tool for predicting individual LNM in CRC patients.

A nomogram based on collagen signature for predicting the immunoscore in colorectal cancer.

Objectives: The Immunoscore can categorize patients into high- and low-risk groups for prognostication in colorectal cancer (CRC). Collagen plays an important role in immunomodulatory functions in the tumor microenvironment (TME). However, the correlation between collagen and the Immunoscore in the TME is unclear. This study aimed to construct a collagen signature to illuminate the relationship between collagen structure and Immunoscore. Methods: A total of 327 consecutive patients with stage I-III stage CRC were included in a training cohort. The fully quantitative collagen features were extracted at the tumor center and invasive margin of the specimens using multiphoton imaging. LASSO regression was applied to construct the collagen signature. The association of the collagen signature with Immunoscore was assessed. A collagen nomogram was developed by incorporating the collagen signature and clinicopathological predictors after multivariable logistic regression. The performance of the collagen nomogram was evaluated via calibration, discrimination, and clinical usefulness and then tested in an independent validation cohort. The prognostic values of the collagen nomogram were assessed using Cox regression and the Kaplan-Meier method. Results: The collagen signature was constructed based on 16 collagen features, which included 6 collagen features from the tumor center and 10 collagen features from the invasive margin. Patients with a high collagen signature were more likely to show a low Immunoscore (Lo IS) in both cohorts (P<0.001). A collagen nomogram integrating the collagen signature and clinicopathological predictors was developed. The collagen nomogram yielded satisfactory discrimination and calibration, with an AUC of 0.925 (95% CI: 0.895-0.956) in the training cohort and 0.911 (95% CI: 0.872-0.949) in the validation cohort. Decision curve analysis confirmed that the collagen nomogram was clinically useful. Furthermore, the collagen nomogram-predicted subgroup was significantly associated with prognosis. Moreover, patients with a low-probability Lo IS, rather than a high-probability Lo IS, could benefit from chemotherapy in high-risk stage II and stage III CRC patients. Conclusions: The collagen signature is significantly associated with the Immunoscore in the TME, and the collagen nomogram has the potential to individualize the prediction of the Immunoscore and identify CRC patients who could benefit from adjuvant chemotherapy.

Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction.

OBJECTIVE: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. METHOD: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. RESULT: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. CONCLUSIONS: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

Comparison of the Efficacy of Endoscopic Radial Incision and Cutting Procedure and Endoscopic Balloon Dilation for Benign Anastomotic Stricture After Low Anterior Resection Combined With Preventive Loop Ileostomy in Rectal Cancer.

BACKGROUND: Endoscopic radial incision and cutting procedure is a notable technique in the treatment of benign anastomotic strictures after low anterior resection in rectal cancer. However, the efficacy and safety of the endoscopic radial incision and cutting procedure and traditional endoscopic balloon dilation remain unknown. OBJECTIVE: To compare the efficacy and safety of the endoscopic radial incision and cutting procedure and endoscopic balloon dilation in patients with anastomotic stricture after low anterior resection. DESIGN: Rectal cancer patients with anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy between January 2014 and June 2021 were retrospectively collected. These patients underwent the endoscopic radial incision and cutting procedure or endoscopic balloon dilation as an initial treatment. The clinicopathological baseline data of the patients, endoscopic surgery success rate, complications, and restricture rate were analyzed. SETTINGS: This study was conducted at Nanfang Hospital in China. PATIENTS: A total of 30 patients were eligible after reviewing the medical records. Twenty patients underwent endoscopic balloon dilation, and 10 patients underwent endoscopic radial incision and cutting procedure. MAIN OUTCOME MEASURES: The adverse event rate and stricture recurrence rate. RESULTS: There were no significant differences in patient demographics or clinical features. No adverse events occurred in either of the 2 groups. The mean operation time was 18.9 ± 3.6 minutes in the endoscopic balloon dilation group and 10.2 ± 3.3 minutes in the endoscopic radial incision and cutting procedure group ( p < 0.001). The stricture recurrence rates between the endoscopic balloon dilation group and the endoscopic radial incision and cutting procedure group were significantly different (44.4% vs 0%; p = 0.025). LIMITATIONS: This was a retrospective study. CONCLUSIONS: The endoscopic radial incision and cutting procedure is safe and more efficacious than endoscopic balloon dilation for anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy in rectal cancer.

Weighted gene co-expression network analysis identifies the prognosis-related models of left- and right-sided colon cancer.

Left-sided colon cancer (LC) and right-sided colon cancer (RC) are 2 essentially different diseases, and the potential mechanisms regulating them remain unidentified. In this study, we applied weighted gene co-expression network analysis (WGCNA) to confirm a yellow module, mainly enriched in metabolism-related signaling pathways related to LC and RC. Based on the RNA-seq data of colon cancer in The Cancer Genome Atlas (TCGA) and GSE41258 dataset with their corresponding clinical information, a training set (TCGA: LC: n = 171; RC: n = 260) and a validation set (GSE41258: LC: n = 94; RC: n = 77) were divided. Least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis identified 20 prognosis-related genes (PRGs) and helped constructed 2 risk (LC-R and RC-R) models in LC and RC, respectively. The model-based risk scores accurately performed in risk stratification for colon cancer patients. The high-risk group of the LC-R model showed associations with ECM-receptor interaction, focal adhesion, and PI3K-AKT signaling pathway. Interestingly, the low-risk group of the LC-R model showed associations with immune-related signaling pathways like antigen processing and presentation. On the other hand, the high-risk group of the RC-R model showed enrichment for cell adhesion molecules and axon guidance signaling pathways. Furthermore, we identified 20 differentially expressed PRGs between LC and RC. Our findings provide new insights into the difference between LC and RC, and uncover the potential biomarkers for the treatment of LC and RC.

Identification of intestinal microbiome associated with lymph-vascular invasion in colorectal cancer patients and predictive label construction.

Objective: To identify differences between the composition, abundance, and biological function of the intestinal microbiome of patients with and without lymph-vascular invasion (LVI) colorectal cancer (CRC) and to construct predictive labels to support accurate assessment of LVI in CRC. Method: 134 CRC patients were included, which were divided into two groups according to the presence or absence of LVI, and their intestinal microbiomes were sequenced by 16SrRNA and analyzed for differences. The transcriptome sequencing data of 9 CRC patients were transformed into immune cells abundance matrix by CIBERSORT algorithm, and the correlation among LVI-associated differential intestinal microbiomes, immune cells, immune-related genes and LVI-associated differential GO items and KEGG pathways were analyzed. A random forest (RF) and eXtreme Gradient Boosting (XGB) model were constructed to predict the LVI of CRC patients based on the differential microbiome. Result: There was no significant difference in α-diversity and ß-diversity of intestinal microbiome between CRC patients with and without LVI (P > 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis showed 34 intestinal microbiomes enriched in CRC patients of the LVI group and 5 intestinal microbiomes were significantly enriched in CRC patients of the non-lymph-vascular invasion (NLVI) group. The RF and XGB prediction models constructed with the top 15% of the LVI-associated differential intestinal microbiomes ranked by feature significance had good efficacy. Conclusions: There are 39 intestinal flora with significantly different species abundance between the LVI and NLVI groups. g:Alistipes.s:Alistipes_indistinctus is closely associated with colorectal cancer vascular invasion. LVI-associated differential intestinal flora may be involved in regulating the infiltration of immune cells in CRC and influencing the expression of immune-related genes. LVI-associated differential intestinal flora may influence the process of vascular invasion in CRC through a number of potential biological functions. RF prediction models and XGB prediction models constructed based on microbial markers of gut flora can be used to predict CRC-LVI conditions.

Posterior reversible encephalopathy syndrome in a child after burns: A case report and literature review.

Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that are usually reversible. However, there are only few reports of burns with posterior reversible encephalopathy syndrome in the literature. Hence, it is a clinical entity that many burn medicine physicians may be unfamiliar with. We report a case of severe burns complicated by posterior reversible encephalopathy syndrome in a 14-month-old male patient. On the eighth day of hospitalization, the child had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Magnetic resonance imaging on day 10 showed the diagnosis is posterior reversible encephalopathy syndrome. We used hormone therapy to reduce cerebral oedema, oxcarbazepine to control convulsions, and multiple other drugs and physical measures to treat fever. The symptoms, signs, and imaging abnormalities of his posterior reversible encephalopathy syndrome were rapidly reversed in a short period of time. At the 1-year follow-up, the patient had recovered completely with no residual neurological signs and symptoms. To our knowledge, the patient may be the youngest recorded patient with both burns and posterior reversible encephalopathy syndrome. Careful observation, computed tomography, and magnetic resonance imaging can achieve early detection, early diagnosis, and early treatment of posterior reversible encephalopathy syndrome, which facilitates the achievement of desired therapeutic results. Further investigation is required to determine whether burns can serve as an independent posterior reversible encephalopathy syndrome causative factor and clarify the underlying pathogenesis mechanism.

A Clinicopathological Feature-Based Nomogram for Predicting the Likelihood of D3 Lymph Node Metastasis in Right-Sided Colon Cancer Patients.

BACKGROUND: Despite advancements in treating right-sided colon cancer patients, the ideal scope of lymphadenectomy remains controversial. OBJECTIVE: Our objective was to investigate the likelihood of D3 lymph node metastasis in right-sided colon cancer patients and develop a clinicopathological feature-based nomogram for D3 lymphadenectomy. DESIGN: We retrospectively analyzed 286 right-sided colon cancer patients who underwent D3 lymphadenectomy. The patients were divided into 2 groups based on whether D3 lymph node metastasis was positive. Then, univariable and multivariable logistic regression analyses were performed to obtain independent risk factors for predicting D3 lymph node metastasis. Moreover, we performed receiver operating characteristic curve analyses to evaluate the predictive power of the model. SETTING: This study was conducted at Nanfang Hospital of Southern Medical University in China. PATIENTS: A total of 286 consecutive patients who underwent right hemicolectomy and D3 lymphadenectomy as a primary treatment for right-sided colon cancer between January 2016 and December 2019 were enrolled in this study. MAIN OUTCOME MEASURES: The primary measures were independent risk factors for predicting D3 lymph node metastasis in right-sided colon cancer. RESULTS: The D3 lymph node metastasis rate in right-sided colon cancer patients was 16.1% (46/286). D3 lymphadenectasis on CT, lymphatic invasion, and T4 tumors were filtered out as independent risk factors for D3 lymph node metastasis according to the multivariable logistic regression analysis. We established a nomogram that predicted D3 lymph node metastasis of right-sided colon cancer on the combination of the 3 factors with an area under the curve of 0.717 (95% CI, 0.629-0.806). LIMITATIONS: This was a retrospective study from a single center. CONCLUSIONS: We developed a valuable clinicopathological feature-based nomogram to predict the incidence of D3 lymph node metastasis in right-sided colon cancer patients. Patients with D3 lymphadenectasis on CT, preoperative T4 tumors, and lymphatic invasion should undergo D3 lymphadenectomy. See Video Abstract at http://links.lww.com/DCR/B852 . UN NOMOGRAMA BASADO EN CARACTERSTICAS CLNICOPATOLGICAS PARA PREDECIR LA PROBABILIDAD DE METSTASIS EN GANGLIOS LINFTICOS D EN PACIENTES CON CNCER DE COLON DERECHO: ANTECEDENTES:A pesar de los avances en el tratamiento de pacientes con cáncer de colon derecho, el ámbito ideal de la linfadenectomía sigue siendo controvertido.OBJETIVO:Investigar la probabilidad de metástasis en los ganglios linfáticos D3 en pacientes con cáncer de colon derecho y desarrollar un nomograma basado en características clínico-patológicas basado para la linfadenectomía D3.DISEÑO:Analizamos retrospectivamente a 286 pacientes con cáncer de colon derecho que se sometieron a linfadenectomía D3. Los pacientes se dividieron en dos grupos en función de si eran positivos para metástasis en los ganglios linfáticos D3. Luego, se realizaron análisis de regresión logística univariable y multivariable para obtener factores de riesgo independientes para predecir metástasis en los ganglios linfáticos D3. Además, realizamos análisis de las curvas de características operatorias del receptor para evaluar el poder predictivo del modelo.SEDE:Este estudio se realizó en el Hospital Nanfang de la Universidad Médica del Sur en China.PACIENTES:Un total de 286 pacientes consecutivos que se sometieron a hemicolectomía derecha y linfadenectomía D3 como tratamiento primario para el cáncer de colon derecho entre enero de 2016 y diciembre de 2019 se inscribieron en este estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron factores de riesgo independientes para predecir las metástasis en ganglios linfáticos D3 en el cáncer de colon derecho.RESULTADOS:La tasa de metástasis en los ganglios linfáticos D3 en pacientes con cáncer de colon del lado derecho fue del 16,1% (46/286). El aumento de tamaño de ganglios D3 en la TC, la invasión linfática y los tumores T4 se filtraron como factores de riesgo independientes de metástasis en los ganglios linfáticos D3 de acuerdo con el análisis de regresión logística multivariable. Establecimos un nomograma que predijo metástasis en los ganglios linfáticos D3 del cáncer de colon derecho en la combinación de los tres factores con un área bajo la curva de 0,717 (IC del 95%, 0,629-0,806).LIMITACIONES:Este fue un estudio retrospectivo de un solo centro.CONCLUSIONES:Desarrollamos un valioso nomograma basado en características clínico-patológicas para predecir la incidencia de metástasis en los ganglios linfáticos D3 en pacientes con cáncer de colon derecho. Los pacientes con crecimiento de ganglios D3 en TC, tumores con clasificación preoperatoria T4 e invasión linfática, deben ser sometidos a linfadenectomía D3. Consulte Video Resumen en http://links.lww.com/DCR/B852 . (Traducción-Dr. Juan Carlos Reyes ).

Case Report: Colon malignant tumor caused by retroperitoneal small round cell undifferentiated sarcoma.

Small round cell undifferentiated sarcoma is a rare and highly invasive group of malignant bone and soft tissue tumors, often associated with a high misdiagnosis rate. The patient in this case was a 34-year-old male who presented with a two-month history of abdominal pain that worsened over the past two weeks. Elevated levels of tumor markers CA19-9 and CA72-4 were observed. Imaging revealed a substantial, well-vascularized mass in the lower left abdomen, located in the posterior abdominal cavity, invading the descending colon and the root of the small mesentery, and infiltrating the serous layer. The lesion was extensively resected without any postoperative complications. Microscopic examination indicated a combination of mucinous adenocarcinoma (approximately 30%) and small round cell undifferentiated sarcoma (approximately 70%). The patient was followed up for six months, and one month after surgery, a recurrence of the tumor was observed in the left paracolonic sulcus area, with metastases to the abdominal wall, peritoneum, and medial iliac muscles. Chemotherapy and targeted therapy were administered, and the patient currently survives with the presence of tumors. Small round cell undifferentiated sarcoma is an uncommon and highly invasive tumor, and clinical surgeons need to raise their awareness and realize to the maximum extent possible that this disease can be described through a multi-modal combination of immunohistochemistry and genetic test to improve diagnostic accuracy and reduce missed diagnoses. Further research in the field of biology is necessary to explore targeted drugs specifically suitable for this disease.

Comprehensive multi-omics analysis of the m7G in pan-cancer from the perspective of predictive, preventive, and personalized medicine.

Background: The N7-methylguanosine modification (m7G) of the 5' cap structure in the mRNA plays a crucial role in gene expression. However, the relation between m7G and tumor immune remains unclear. Hence, we intended to perform a pan-cancer analysis of m7G which can help explore the underlying mechanism and contribute to predictive, preventive, and personalized medicine (PPPM / 3PM). Methods: The gene expression, genetic variation, clinical information, methylation, and digital pathological section from 33 cancer types were downloaded from the TCGA database. Immunohistochemistry (IHC) was used to validate the expression of the m7G regulator genes (m7RGs) hub-gene. The m7G score was calculated by single-sample gene-set enrichment analysis. The association of m7RGs with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. CellProfiler was used to extract pathological section characteristics. XGBoost and random forest were used to construct the m7G score prediction model. Single-cell transcriptome sequencing (scRNA-seq) was used to assess the activation state of the m7G in the tumor microenvironment. Results: The m7RGs were highly expressed in tumors and most of the m7RGs are risk factors for prognosis. Moreover, the cellular pathway enrichment analysis suggested that m7G score was closely associated with invasion, cell cycle, DNA damage, and repair. In several cancers, m7G score was significantly negatively correlated with MSI and TMB and positively correlated with TIDE, suggesting an ICB marker potential. XGBoost-based pathomics model accurately predicts m7G scores with an area under the ROC curve (AUC) of 0.97. Analysis of scRNA-seq suggests that m7G differs significantly among cells of the tumor microenvironment. IHC confirmed high expression of EIF4E in breast cancer. The m7G prognostic model can accurately assess the prognosis of tumor patients with an AUC of 0.81, which was publicly hosted at https://pan-cancer-m7g.shinyapps.io/Panca-m7g/. Conclusion: The current study explored for the first time the m7G in pan-cancer and identified m7G as an innovative marker in predicting clinical outcomes and immunotherapeutic efficacy, with the potential for deeper integration with PPPM. Combining m7G within the framework of PPPM will provide a unique opportunity for clinical intelligence and new approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00305-1.

Prognostic and predictive value of a pathomics signature in gastric cancer.

The current tumour-node-metastasis (TNM) staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer (GC). Pathomics, which is based on the development of digital pathology, is an emerging field that might improve clinical management. Herein, we propose a pathomics signature (PSGC) that is derived from multiple pathomics features of haematoxylin and eosin-stained slides. We find that the PSGC is an independent predictor of prognosis. A nomogram incorporating the PSGC and TNM staging system shows significantly improved accuracy in predicting the prognosis compared to the TNM staging system alone. Moreover, in stage II and III GC patients with a low PSGC (but not in those with a high PSGC), satisfactory chemotherapy benefits are observed. Therefore, the PSGC could serve as a prognostic predictor in patients with GC and might be a potential predictive indicator for decision-making regarding adjuvant chemotherapy.

Intestinal intussusception caused by intestinal duplication and ectopic pancreas: A case report and review of literature.

BACKGROUND: Intestinal intussusception caused by intestinal duplication and ectopic pancreas is extremely rare in the clinic and has not been reported previously. CASE SUMMARY: A 29-year-old man was admitted to the hospital for chronic abdominal pain and bloating. The preoperative diagnosis was intestinal obstruction and intussusception. Then, laparotomy, partial small intestinal resection and extraintestinal decompression were performed. Postoperative pathology confirmed intestinal duplication and ectopic pancreas. After surgery, the patient recovered well with no complications. No recurrence was observed after more than 5 mo of follow-up. CONCLUSION: We report a new case of a young male with intussusception caused by intestinal duplication and ectopic pancreas. Surgery is the main treatment for these conditions. This study aimed to raise awareness and provide information to improve the clinical management of this rare yet serious condition.

Prognostic role and clinical significance of C-reactive protein-lymphocyte ratio in colorectal cancer.

Systemic inflammatory response (SIRS) can be used as a potential prognostic marker in patients with colorectal cancer (CRC). The purpose of this study was to examine the predictive role of the C-reactive protein (CRP)-lymphocyte ratio (CLR) in the prognosis of CRC. We retrospectively analyzed the data of CRC patients who underwent surgery from 2004 to 2019. The clinicopathological characteristics and follow-up records were analyzed. According to a cutoff value of CLR, the patients were divided into the high and low groups. Kaplan-Meier curves and Cox proportional hazards regression model were applied to assess the overall survival (OS). Clinicopathological characteristics analysis showed that gender, age, BMI, lymphocyte count, tumor location, left- and right-sided CRC, differentiation, T stage, M stage, TNM stage, carcinoembryonic antigen (CEA), CLR, CRP, and microsatellite status were found to differ significantly between the high and low CLR groups. Kaplan-Meier curves revealed that the high CLR group had a shorter OS, and the elderly or right-sided CRC patients faced a worse prognosis. Multivariate analysis suggested that age (hazard ratio [HR]:1.011, P = 0.003), differentiation (HR:1.331, P = 0.000), TNM stage (HR:2.425, P = 0.000), CEA (HR:1.001, P = 0.025), CLR (HR:1.261, P = 0.014) were significant independent prognostic factors for OS. Subgroup analysis demonstrated that females or patients not receiving postoperative adjuvant chemotherapy with high CLR might suffer a worse prognosis. Overall, CLR can be applied as a promising prognostic marker in CRC patients and has great potential in guiding clinical work.

Prognostic Value of Combined Preoperative Carcinoembryonic Antigen and Prognostic Nutritional Index in Patients With Stage II-III Colon Cancer.

Background: Tumor status can affect patient prognosis. Prognostic nutritional index (PNI), as a nutritional indicator, is closely related to the prognosis of cancer. However, few studies have examined the combined prognostic value of CEA and PNI in patients. This study investigated the relationship between CEA/PNI and prognosis of colon cancer patients. Methods: A total of 513 patients with stage II-III colon cancer who underwent curative resection at two medical centers from 2009 to 2019 were included. Clinicopathological factors were assessed and overall survival (OS) was assessed in a cohort of 413 patients. Multivariate analysis was used to identify independent prognostic variables to construct histograms predicting 1-year and 3-year OS. Data from 100 independent patients in the validation group was used to validate the prognostic model. Results: The median OS time was 33.6 months, and mortality was observed in 54 patients. Multivariate analysis revealed that preoperative CEA/PNI, lymph node metastasis, peripheral nerve invasion, operation mode, and postoperative chemotherapy were independent factors for prognosis evaluation and thus were utilized to develop the nomogram. The C-index was 0.788 in the learning set and 0.836 in the validation set. The calibration curves reached favorable consensus among the 1-, 3-year OS prediction and actual observation. Conclusion: The combined use of CEA and PNI is an independent prognostic factor and thus can serve as a basis for a model to predict the prognosis of patients with stage II-III colon cancer.

Perianal superficial CD34-positive fibroblastic tumor: A case report.

BACKGROUND: Superficial CD34-positive fibroblast tumors (SCPFTs) are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors. To the best of our knowledge, fewer than 50 cases have been reported. Perianal SCPFT has not been previously reported. CASE SUMMARY: A 55-year-old man was hospitalized upon discovering a painless perianal lump 10 d prior. Physical examination showed a lump of approximately 3 cm × 4 cm in the 7 to 8 o'clock direction in the perianal area. Perianal abscess was considered the primary diagnosis. Lump removal surgery was performed under epidural anesthesia. Postoperative pathology showed a well-circumscribed, soft tissue-derived, spindle-cell tumor with strong CD34 positivity by immunohistochemistry. The final diagnosis was perianal SCPFT. There were no complications, and the patient was followed for more than 8 mo without recurrence or metastasis. CONCLUSION: We report a case of perianal superficial CD34-positive fibroblast tumor. This rare mesenchymal neoplasm has distinctive histomorphology, which is important for diagnosis. Comprehensive consideration of clinical information, imaging, histology, and immunohistochemistry is important for diagnosis.

Preoperative Predictors of Lymph Node Metastasis in Colon Cancer.

BACKGROUND: Lymph node metastasis (LNM) is a well-established prognostic factor for colon cancer. Preoperative LNM evaluation is relevant for planning colon cancer treatment. The aim of this study was to construct and evaluate a nomogram for predicting LNM in primary colon cancer according to pathological features. PATIENTS AND METHODS: Six-hundred patients with clinicopathologically confirmed colon cancer (481 cases in the training set and 119 cases in the validation set) were enrolled in the Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to December 2019. The expression of molecular markers (p53 and ß-catenin) was determined by immunohistochemistry. Multivariate logistic regression was used to screen out independent risk factors, and a nomogram was established. The accuracy and discriminability of the nomogram were evaluated by consistency index and calibration curve. RESULTS: Univariate logistic analysis revealed that LNM in colon cancer is significantly correlated (P <0.05) with tumor size, grading, stage, preoperative carcinoembryonic antigen (CEA) level, and peripheral nerve infiltration (PNI). Multivariate logistic regression analysis confirmed that CEA, grading, and PNI were independent prognostic factors of LNM (P <0.05). The nomogram for predicting LNM risk showed acceptable consistency and calibration capability in the training and validation sets. CONCLUSIONS: Preoperative CEA level, grading, and PNI were independent risk factor for LNM. Based on the present parameters, the constructed prediction model of LNM has potential application value.

Cyclooxygenase-2 promoter 765C increase of digestive tract cancer risk in the Chinese population: a meta-analysis.

BACKGROUND: To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism and digestive cancer risk in China. MATERIALS AND METHODS: A literature search through February 2014 was performed using PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. RESULTS: In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis.The pooled OR (95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vs GG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type, significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. No significant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. CONCLUSIONS: These findings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreatic cancer risk.