Clinical efficacy of different approaches for laparoscopic intersphincteric resection of low rectal cancer: a comparison study.

BACKGROUND: The operative results of different approaches for the laparoscopic intersphincteric resection (LAISR) of low rectal cancer vary, and the patient characteristics associated with the best outcomes for each procedure have not been reported. We compared the efficacy of different approaches for LAISR of low rectal cancer and discussed the surgical indications for each approach. METHODS: We retrospectively reviewed data from 235 patients with low rectal cancer treated via LAISR from October 2010 to September 2016. Patients underwent either the transabdominal approach for ISR (TAISR, n = 142), the transabdominal perineal approach for ISR (TPAISR, n = 57), or the transanal pull-through approach for ISR (PAISR, n = 36). RESULTS: The PAISR and TAISR groups exhibited shorter operation times and less intraoperative blood loss than the TPAISR group. The anastomotic distance was shorter in the PAISR and TPAISR groups than in the TAISR group. No differences in the ability to perform radical resection, overall complications, postoperative recovery, Wexner score recorded 12 months after ostomy closure, 3-year disease-free survival, local recurrence-free survival, distant metastasis-free survival, or overall survival (OS) were observed among the three groups. CONCLUSIONS: TAISR, TPAISR, and PAISR have unique advantages and do not differ in terms of operation safety, patient outcomes, or anal function. TPAISR requires a longer time to complete and is associated with more bleeding and a slower recovery of anal function. PAISR should be considered when TAISR cannot ensure a negative distal margin and the tumor and BMI are relatively small; otherwise, TPAISR is required.

Sulfasalazine, a potent suppressor of gastric cancer proliferation and metastasis by inhibition of xCT: Conventional drug in new use.

The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK-8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up-regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK-8 assays revealed that sulfasalazine could attenuate the proliferation of HGC-27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC-27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC-27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.

Risk factors for lymph node metastasis in rectal neuroendocrine tumors: A recursive partitioning analysis based on multicenter data.

BACKGROUND: The well-differentiated rectal neuroendocrine tumors (RNETs) can also have lymph node metastasis (LNM). Large multicenter data were reviewed to explore the risk factors for LNM in RNETs. Further, we developed a model to predict the risk of LNM in RNETs. METHODS: In total, 223 patients with RNETs from the Fujian Medical University Union Hospital, the First Affiliated Hospital of Fujian Medical University, and the First Affiliated Hospital of Xiamen University were retrospectively enrolled. Logistic regression analysis was performed to study the factors affecting LNM, and recursive partitioning analysis (RPA) was performed to stratify the risk of LNM. RESULTS: Among the 223 patients diagnosed with RNETs, the incidence of LNM was 10.8%. Univariate and multivariate regression analyses revealed that tumor size, World Health Organization (WHO) grade, and depth of tumor invasion were independent risk factors for LNM (p < 0.05). The area under the curve was 0.948 (95% confidence interval: 0.890-1.000). Furthermore, the incidence of LNM in patients divided into low- and high-risk groups according to RPA was 1.1% and 56.4%, respectively. CONCLUSION: Compared with tumor size, the depth of tumor invasion and WHO grade are more important factors in predicting LNM. Then, we developed a model based on RPA to predict the risk of LNM in RNETs and identify patients who are suitable for local resection.

Clinical analysis of metastatic characteristics of infrapyloric lymph nodes (No.206) and terminal ileum lymph nodes in patients with right colon cancer.

BACKGROUND: D3 or complete mesocolic excision (CME) surgery has become a common surgical procedure for the treatment of colon cancer metastasis. Clinical misuse and overuse of lymph node dissection bring unnecessary burdens to patients. A detailed guidance for lymph node dissection in patients with T3 and T4 stage right colon cancer at different locations is urgently needed. METHODS: A retrospective study was performed. Patients received D3 or CME surgery were divided into ileocecal group, ascending colon group, and hepatic flexure group according to the 9th edition of the Japanese Society for Cancer of the Colon and Rectum guidelines. The distributions of lymph node metastases were analyzed according to tumor infiltration depth (T stage) and tumor location. RESULTS: The incidence of metastases in the paracolic area (or station), intermediate area, and main (or central) area was 38.4% (139/362), 12.7% (46/362), and 9.7% (35/362), respectively. The proportion of patients having No.206 and terminal ileum lymph nodes metastases was 7.7% (14/181) and 3.7% (9/244), respectively. No.206 lymph node metastasis is related to tumor location (χ2 = 7.955, p = 0.019) and degree of differentiation (χ2 = 18.99, p = 0.000), and terminal ileum lymph node metastasis is related to tumor location (χ2 = 6.273, p = 0.043). Patients with T3/T4 hepatic flexure cancer received radical right hemicolectomy in addition to No.206 lymph node dissection. CONCLUSION: Radical right hemicolectomy and No.206 group lymph node dissection are necessary for T3 and T4 stage colon cancer therapy.

m6 A RNA methylation regulators contribute to malignant progression in rectal cancer.

N6,2'-O-dimethyladenosine (m6 A) RNA methylation, which is correlated with cancer initiation and progression, is dynamically regulated by m6 A RNA methylation regulators, including writers, erasers, and readers. Two subgroups of rectal cancer, including cluster1 and cluster2, were identified based on consensus clustering to m6 A RNA methylation regulators. A protein-protein interaction network was constructed and hub genes were identified. The results demonstrated that the expression of WTAP was significantly associated with YTHDC1 and YTHDF2. The principal component analysis was used to compare the transcriptional profile between cluster1 and cluster2 subgroups. By using two identified m6 A RNA methylation regulators, we constructed a risk signature to predict the survival outcomes of rectal cancer. The results revealed that YTHDC2 and YTHDF2 were protective genes with HR < 1. The coefficients obtained from the least absolute shrinkage and selection operator algorithm were used to calculate the risk score. Patients were then divided into low- and high-risk groups based on the median risk score. The survival analysis demonstrated that there were significant differences in overall survival between these two groups (p < .05). The results of the univariate analysis showed that the risk score, AJCC stage, M stage, and age were associated with overall survival. The results of the multivariate Cox regression analysis showed that the risk score and age were still significantly associated with the overall survival (p < .05). To conclude, m6 A RNA methylation regulators can be regarded as potentially useful biomarkers for predicting the prognosis and designing a treatment strategy in rectal cancer.

TMEM100 expression suppresses metastasis and enhances sensitivity to chemotherapy in gastric cancer.

The gene encoding transmembrane protein 100 (TMEM100) was first discovered to be transcribed by the murine genome. It has been recently proven that TMEM100 contributes to hepatocellular carcinoma and non-small-cell lung carcinoma (NSCLC). This study investigates the impact of TMEM100 expression on gastric cancer (GC). TMEM100 expression was remarkably downregulated in GC samples compared to the surrounding non-malignant tissues (p < 0.01). Excessive TMEM100 expression prohibited the migration and invasion of GC cells without influencing their growth. However, TMEM100 knockdown restored their migration and invasion potential. Additionally, TMEM100 expression restored the sensitivity of GC cells to chemotherapeutic drugs such as 5-fluouracil (5-FU) and cisplatin. In terms of TMEM100 modulation, it was revealed that BMP9 rather than BMP10, is the upstream modulator of TM3M100. HIF1α downregulation modulated the impact of TMEM100 on cell migration, chemotherapy sensitivity and invasion in GC cells. Eventually, the in vivo examination of TMEM100 activity revealed that its upregulation prohibits the pulmonary metastasis of GC cells and increases the sensitivity of xenograft tumors to 5-FU treatment. In conclusion, TMEM100 serves as a tumor suppressor in GC and could be used as a promising target for the treatment of GC and as a predictor of GC clinical outcome.

LPS Upregulated VEGFR-3 Expression Promote Migration and Invasion in Colorectal Cancer via a Mechanism of Increased NF-κB Binding to the Promoter of VEGFR-3.

BACKGROUND AND AIM: Lipopolysaccharide(LPS) could promote the progression of colorectal cancer, but the specific regulatory mechanisms are largely unknown. So, this study aim to clarify the mechanisms that LPS upregulated VEGFR-3, which promotes colorectal cancer cells migration and invasion with a mechanism of increased NF-κB bind to the promoter of VEGFR-3. METHODS: The present study examined the VEGFR-3 expression in colorectal cancer tissues and analyzed the relationship between the VEGFR-3 expression with clinical parameters. PCR, Western blot, CCK-8, colone formation assay, and Transwell assay detected that LPS promoted the migration and invasion and the role of VEGFR-3 in the process of colorectal carcinoma in vitro. Used the methods of promoter analysis, EMSA assay and ChIP assay to explore the mechanisms LPS increased the expression of VEGFR-3. RESULTS: VEGFR-3 was significantly high expression in the colorectal cancer tissues. And the high expression was associated with the TNM stage and lymph node metastasis of colorectal cancer. LPS could promote the migration and invasion, which could be blocked by the neutralizing antibody IgG of VEGFR-3. And found that -159 nt to +65 nt was the crucial region of VEGFR-3 promoter. And detected that the NF-κB was important transcription factor for the VEGFR-3 promoter. And LPS could increase NF-κB binding to VEGFR-3 promoter and upregulated the expression of VEGFR-3 to exert biological functions. CONCLUSION: We have elucidated the relationship between LPS and the VEGFR-3 expression and revealed that VEGFR-3 play very important role in the process of LPS promoting the migration and invasion of colorectal cancer cells. Further illuminated the mechanism that LPS upregulated VEGFR-3 expression via increased NF-κB bind to the promoter of VEGFR-3.

Novel nomograms based on microvascular invasion grade for early-stage hepatocellular carcinoma after curative hepatectomy.

Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). This study aimed to firstly develop and validate nomograms based on MVI grade for predicting recurrence, especially early recurrence, and overall survival in patients with early-stage HCC after curative resection. We retrospectively reviewed the data of patients with early-stage HCC who underwent curative hepatectomy in the First Affiliated Hospital of Fujian Medical University (FHFU) and Mengchao Hepatobiliary Hospital of Fujian Medical University (MHH). Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse disease-free survival (DFS) and overall survival (OS). Nomogram models were constructed on the datasets from the 70% samples of and FHFU, which were validated using bootstrap resampling with 30% samples as internal validation and data of patients from MHH as external validation. A total of 703 patients with early-stage HCC were included to create a nomogram for predicting recurrence or metastasis (DFS nomogram) and a nomogram for predicting survival (OS nomogram). The concordance indexes and calibration curves in the training and validation cohorts showed optimal agreement between the predicted and observed DFS and OS rates. The predictive accuracy was significantly better than that of the classic HCC staging systems.

Conditional survival nomogram for patients with colon mucinous adenocarcinoma to predict prognosis: a dynamic survival analysis.

The aim was to assess conditional survival for colon mucinous adenocarcinoma (MAC) patients, and to construct nomograms to predict conditional survival probability. Survival analysis was done using conditional survival, which was defined as the probability of surviving additional y years for patients who have survived for x years. The mathematical definition was express as: CS (y|x) = S (x + y)/S (x). Cox regression analyses were used to identify prognostic factors. A nomogram is constructed to predict conditional disease-free survival (DFS) and overall survival (OS) probability according to years that already survive. A total of 179 colon MAC patients were included. The 5-year DFS was 67% after surgery, and the 5-year survival probability of patients, who already survived 1, 2, 3, and 4 years were 75%, 87%, 95%, and 98%, respectively. The 5-year OS was 73% after surgery and increased to 76%, 82%, 88%, and 92% at 1, 2, 3, and 4 years, respectively. Subgroup analyses demonstrated the superiority of conditional survival was more pronounced in advanced stages than in stage I. And pT stage, pN stage, and lymphovascular invasion were significantly associated with DFS and OS. Conditional survival nomograms were constructed to predict the 5-year conditional DFS and OS probability given survival for 1, 2, 3, 4 years after surgery. Conditional survival can provide dynamic survival probability according to years that already survive, especially for patients with advanced stages. Taking into account the years already survived accounted for, novel nomograms contributed to effectively predicting conditional survival.

The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer.

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

A modified mTNM staging system based on lymph node ratio for colon neuroendocrine tumors: A recursive partitioning analysis.

Background: In the current tumor-lymph node-metastasis (TNM) staging system for colon neuroendocrine tumors, lymph node status is divided into N1 and N0. An assessment of the lymph node ratio (LNR) and a proposal for a modified mTNM staging system were the objectives of this study. Methods: Selecting the optimal cut-off value of LNR was done using X-tile. A Cox regression model and the Kaplan-Meier method were performed to calculate patient cancer-specific survival in the Surveillance, Epidemiology and End Results cohort. Recursive partitioning analysis was used to improve TNM staging. Results: The study included 674 patients. The current TNM staging system showed inadequate discriminatory power between stage I and stage II patients (p = 0.088). The optimal cut-off value was determined as 0.6 for LNR. Based on multivariate Cox regression analysis, the modified mN classification could be classified into mN 0 (LNR = 0.00), mN 1 (LNR = 0.01-0.60), and mN 2 (LNR > 0.60), and was found to be an independent factor affecting prognosis (p < 0.001). Using the American Joint Committee on Cancer T and modified mN classifications, the modified mTNM system was constructed, and it exhibited better prognostic discriminatory power ability than the traditional TNM system (C-index: 0.587 vs. 0.665). Conclusions: Our study determined that LNR is a prognostic factor in colon NET patients. In addition, to more accurately assess the prognosis of colon NET patients, we proposed a modified mTNM staging system.

Double-stapled anastomosis without "dog-ears" reduces the anastomotic leakage in laparoscopic anterior resection of rectal cancer: A prospective, randomized, controlled study.

Background: Anastomotic leakage (AL) is a major cause of postoperative morbidity and mortality in the treatment of colorectal cancer. The aim of this study was to investigate whether the resection of "dog-ears" in laparoscopic anterior resection of rectal cancer (called modified double-stapling technique, MDST) could reduce the rate of AL in patients with middle and high rectal cancer, as compared with the conventional double-stapling technique (DST). Methods: The clinical data of 232 patients with middle and high rectal cancer were prospectively collected from September 2015 to October 2018. They were randomly divided into the MDST group (n = 116) and the DST group (n = 116) and the data were prospectively analyzed. Morbidity and AL rate were compared between the two groups. Results: Patient demographics, tumor size, and time of first flatus were similar between the two groups. No difference was observed in the operation time between the two groups. The AL rate was significantly lower in the MDST group than in the DST group (3.4 vs. 11.2%, p = 0.032). The age and anastomotic technique were the factors associated with AL according to the multivariate analysis. The location of the AL in the DST group was further investigated, revealing that AL was in the same place as the "dog-ears" (11/13, 84.6%). Conclusions: Our prospective comparative study demonstrated that MDST have a better short-term outcome in reducing AL compared with DST. Therefore, this technique could be an alternative approach to maximize the benefit of laparoscopic anterior resection on patients with middle and high rectal cancer. The "dog-ears" create stapled corners potentially ischemic, since they represent the area with high incidence of AL.(NCT:02770911).

Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers.

PURPOSE: To assess the value of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) for predicting the response to neo-chemoradiotherapy (NCRT) and the prognosis of locally advanced rectal cancer (LARC). METHODS: We enrolled 191 patients who underwent neoadjuvant chemoradiotherapy and radical resection between 2011 and 2015. Tumor tissues were collected before NCRT with a colonoscope and post-surgery and were subjected to immunohistochemical analysis. RESULTS: The expression levels of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) were lower in the pathological complete response (pCR) group when compared with the non-pCR group (all P<0.05). Based on X-tile plots, we divided the tumors in two groups and found that lower pre-NCRT/post-surgical CD163, CD68, MCSF, CCL2 scores correlated with improved DFS. Cox regression analysis demonstrated that pre-NCRT CD163 (HR=1.008, 95% CI 1.003-1.013, P=0.003) and MCSF (HR=2.187, 95% CI 1.343-3.564, P=0.002) scores were independent predictors of DFS. Based on Cox multivariate analysis, we constructed a risk score model with a powerful ability to predict pCR in LARC patients. Moreover, COX regression analysis was performed to explore the role of the risk score in LARC patients. The results demonstrated that tumor size (HR=1.291, P=0.041), worse pathological TNM stage (HR=1.789, P=0.005, and higher risk score (HR=1.084, P<0.001) were significantly associated with impaired disease-free survival. Based on the above results, a nomogram and decision curve analysis were generated. CONCLUSION: The expression levels of macrophage-related biomarkers CD163, CD68, MCSF, and CCL2 were associated with chemoradiotherapy resistance and prognosis in LARC patients following NCRT. A risk score model was constructed which could be used to predict LARC outcome.

Prognostic Value of the Distribution of Lymph Node Metastasis in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy.

Background: The objective of this study is to assess the prognostic value of lymph node metastasis distribution (LND) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods: This study included 179 patients with pathological stage III LARC who underwent nCRT followed by radical surgery. LND was classified into three groups: LND1, lymph node metastasis at the mesorectum (140/179, 78.2%); LND2, lymph node metastasis along the inferior mesenteric artery trunk nodes (26/179, 14.5%); LND3, lymph node metastasis at the origin of the IMA (13/179, 7.3%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. Result: LND showed better stratification for 3-year DFS (LND1 66.8, LND2 50, and LND3 15.4%, P < 0.01) compared to the ypN (3-year DFS: N1 59.9 and N2 60.3%, P = 0.34) and ypTNM (3-year DFS: IIIA 68.6%, IIIB 57.5%, and IIIC 53.5, P = 0.19) staging systems. Similar results were found for 3-year LRFS and DMFS. According to multivariate survival analysis, LND was shown to be an independent prognostic factor for DFS, LRFS, and DMFS in patients with positive lymph nodes (P < 0.01, in all cases). Conclusion: LND is an independent prognostic factor in stage III rectal cancer after nCRT. LND can be used as a supplementary indicator for the ypTNM staging system in patients with LARC after nCRT.

Clinical Significance and Oncogenic Activity of GRWD1 Overexpression in the Development of Colon Carcinoma.

OBJECTIVE: GRWD1 (glutamate-rich WD40 repeat containing 1) is a multifunctional protein involved in multiple cellular regulatory pathways, particularly those associated with cell growth control. GRWD1 is represented as a potential oncogene in several cancers, however, the function and mechanism of GRWD1 in the development of colon cancer are still unknown. MATERIALS AND METHODS: IHC was used to detect the expression of GRWD1 in colon carcinoma tissues. CCK-8, colony formation, and EdU were used to measure the cell proliferation after GRWD1 knockdown and overexpression. The distribution of the cell cycle was analyzed by flow cytometry. The effect of GRWD1 knockdown on migration and invasion was analyzed by wound healing and transwell assays. RESULTS: Overexpression of GRWD1 in colon carcinoma tissues was associated with pathological grading, tumor size, N stage, TNM stage, and poor survival. GRWD1 had high sensitivity and specificity in distinguishing colon cancer from noncancerous tissues, and might be served as an independent prognosis in colon carcinoma patients. Knockdown of GRWD1 significantly inhibited the cell proliferation and colony formation, and induced cell cycle arrest and more drug susceptibility, and suppressed the migration and invasion. GRWD1 exhibited these oncogenic activities might be associated with its regulation on the expression of PCNA and Ki67, Cyclin A2 and Cyclin B1, ABCC1 and GSTP1, MTA1 and MTA2. CONCLUSION: GRWD1 may play an oncogenic activity in the development of colon carcinoma and its overexpression was associated with malignant characteristics and poor survival outcome of colon carcinoma. GRWD1 might be a potential target for future therapy.

Development and Validation of a Robust Pyroptosis-Related Signature for Predicting Prognosis and Immune Status in Patients with Colon Cancer.

BACKGROUND: Pyroptosis has been confirmed as a type of inflammatory programmed cell death in recent years. However, the prognostic role of pyroptosis in colon cancer (CC) remains unclear. METHODS: Dataset TCGA-COAD which came from the TCGA portal was taken as the training cohort. GSE17538 from the GEO database was treated as validation cohorts. Differential expression genes (DEGs) between normal and tumor tissues were confirmed. Patients were classified into two subgroups according to the expression characteristics of pyroptosis-related DEGs. The LASSO regression analysis was used to build the best prognostic signature, and its reliability was validated using Kaplan-Meier, ROC, PCA, and t-SNE analyses. And a nomogram based on the multivariate Cox analysis was developed. The enrichment analysis was performed in the GO and KEGG to investigate the potential mechanism. In addition, we explored the difference in the abundance of infiltrating immune cells and immune microenvironment between high- and low-risk groups. And we also predicted the association of common immune checkpoints with risk scores. Finally, we verified the expression of the pyroptosis-related hub gene at the protein level by immunohistochemistry. RESULTS: A total of 23 pyroptosis-related DEGs were identified in the TCGA cohort. Patients were classified into two molecular clusters (MC) based on DEGs. Kaplan-Meier survival analysis indicated that patients with MC1 represented significantly poorer OS than patients with MC2. 13 overall survival- (OS-) related DEGs in MCs were used to construct the prognostic signature. Patients in the high-risk group exhibited poorer OS compared to those in the low-risk group. Combined with the clinical features, the risk score was found to be an independent prognostic factor of CC patients. The above results are verified in the external dataset GSE17538. A nomogram was established and showed excellent performance. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the varied prognostic performance between high- and low-risk groups may be related to the immune response mediated by local inflammation. Further analysis showed that the high-risk group has stronger immune cell infiltration and lower tumor purity than the low-risk group. Through the correlation between risk score and immune checkpoint expression, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) was predicted as a potential therapeutic target for the high-risk group. CONCLUSION: The 13-gene signature was associated with OS, immune cells, tumor purity, and immune checkpoints in CC patients, and it could provide the basis for immunotherapy and predicting prognosis and help clinicians make decisions for individualized treatment.

Value of the log odds of positive lymph nodes for prognostic assessment of colon mucinous adenocarcinoma: Analysis and external validation.

PURPOSE: To evaluate the impact of the log odds of positive lymph nodes (LODDS) on cancer-specific survival (CSS) in colon mucinous adenocarcinoma (MAC) patients, compared with pN stage and the lymph nodes ratio (LNR). METHODS: A total of 10,182 colon MAC patients from the Surveillance, Epidemiology, and End Results database were divided into the training group. The external validation group included 153 patients from Fujian Medical University Union Hospital. The Cox regression method was used to identify prognostic risk factors. Nomograms were evaluated by Harrell's concordance index (C-index) and calibration curves. Recursive partitioning analysis (RPA) was used to develop a novel staging system. RESULTS: Time-dependent receiver operating characteristic curves (ROC) to predict CSS showed the areas under the ROC curve of LODDS were always higher than pN stage and LNR. LNR and LODDS classifications can well distinguish the prognosis of patients with the same pN stage. Cox analyses indicated that age, tumor size, pT stage, pN stage, LNR, and LODDS were independent predictors of CSS (p < 0.05). Based on three lymph nodes classifications, we constructed three prognostic nomograms models for CSS. The C-index of the pN, LNR, and LODDS classification nomograms were 0.746 (95% confidence interval [95% CI]: 0.736-0.756), 0.750 (95% CI: 0.740-0.760), and 0.758 (95% CI: 0.748-0.768), respectively. In external validation, we observed the C-index of LODDS classification nomograms was 0.787 (95% CI: 0.648-0.926). RPA stage, including four stages, was constructed successfully based on pT stage and LNR or LODDS, respectively. The 3-, 5-, and 8-year areas under the ROC curve of LNR-RPA stage and LODDS-RPA stage were superior to tumor-node-metastasis stage. CONCLUSION: LODDS to be a better prognostic factor of CSS for colon MAC patients than pN stage and LNR. A nomogram and RPA stage base on LODDS can provide accurate information for personalized cancer treatment.

Hypermethylation and Downregulation of UTP6 Are Associated With Stemness Properties, Chemoradiotherapy Resistance, and Prognosis in Rectal Cancer: A Co-expression Network Analysis.

BACKGROUND: To identify the hub genes associated with chemoradiotherapy resistance in rectal cancer and explore the potential mechanism. METHODS: Weighted gene co-expression network analysis (WGCNA) was performed to identify the gene modules correlated with the chemoradiotherapy resistance of rectal cancer. RESULTS: The mRNA expression of 31 rectal cancer patients receiving preoperative chemoradiotherapy was described in our previous study. Through WGCNA, we demonstrated that the chemoradiotherapy resistance modules were enriched for translation, DNA replication, and the androgen receptor signaling pathway. Additionally, we identified and validated UTP6 as a new effective predictor for chemoradiotherapy sensitivity and a prognostic factor for the survival of colorectal cancer patients using our data and the GSE35452 dataset. Low UTP6 expression was correlated with significantly worse disease-free survival (DFS), overall survival (OS), and event- and relapse-free survival both in our data and the R2 Platform. Moreover, we verified the UTP6 expression in 125 locally advanced rectal cancer (LARC) patients samples by immunohistochemical analysis. The results demonstrated that low UTP6 expression was associated with worse DFS and OS by Kaplan-Meier and COX regression model analyses. Gene set enrichment and co-expression analyses showed that the mechanism of the UTP6-mediated chemoradiotherapy resistance may involve the regulation of FOXK2 expression by transcription factor pathways. CONCLUSION: Low expression of the UTP6 was found to be associated with chemoradiotherapy resistance and the prognosis of colorectal cancer possibly via regulating FOXK2 expression by transcription factor pathways.