eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation.

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.

Comparison of laparoscopic lateral lymph node dissection for rectal cancer with and without routine resection of the visceral branches of internal iliac artery.

PURPOSE: This study aimed to explore the safety and feasibility of the modified lateral lymph node dissection (LLND) with routine resection of the visceral branches of internal iliac vessels (IIVs) for mid-low-lying rectal cancer. MATERIALS AND METHOD: Consecutive patients undergoing LLND for rectal cancer were divided into the routine visceral branches of the IIVs resection group (RVR group) and the NRVR group (without routine resection). The main outcomes were postoperative complications and the number of lateral lymph nodes harvested. RESULTS: From 2012 to 2021, a total of 75 and 57 patients were included in the RVR and NRVR group, respectively. The operative time was reduced in the RVR group (p = 0.020). No significant difference was observed between the two groups for the incidence of total, major, or minor postoperative complications. Pathologically confirmed LLNM were 24 (32%) patients in the RVR group and 12 (21.1%) in the NRVR group (p = 0.162). The number of lateral lymph nodes harvested had no significant difference between two groups (11 vs. 12, p = 0.329). CONCLUSION: LLND with routine resection of visceral branches of IIVs is safe and feasible, which brings no major complication or long-term urinary disorder.

The same parastomal hernia repairs rate in the different approaches to colostomy.

PURPOSE: This study aimed to compare the parastomal hernia repairs rate in the different approaches to colostomy and investigate the risk factors for parastomal hernia formation in patients with permanent colostomies. METHODS: Consecutive rectal cancer patients who underwent abdominoperineal resection from June 2014 to July 2020 in West China Hospital were divided into two groups according to their surgical approach for permanent colostomies. The impact of different approaches to colostomy on parastomal hernia repairs was determined by comparing a group of patients receiving an extraperitoneal route to colostomy with a group receiving transperitoneal. Potential variables were evaluated first with univariate and then multivariate analyses to identify the risk factors for the formation of parastomal hernia. RESULTS: Two hundred two subjects in the transperitoneal group and 103 in the extraperitoneal group attended the follow-up visit with a median follow-up period of 33 (25th-75th percentiles, 17-46) months. Clinically and radiologically detectable parastomal hernias were present in 76 of 202 (37.6%) and 14 of 103 (13.6%) subjects in the transperitoneal and extraperitoneal groups during the follow-up period (p＜0.01). Besides, 10 of 76 (13.1%) subjects in the transperitoneal group and 2 of 14 (14.3%) subjects in the extraperitoneal group underwent a parastomal hernia operation during the follow-up (p = 0.82). In addition, the transperitoneal approach of colostomy (p = 0.002), older age (p＜0.001), and higher body mass index (p = 0.013) were identified as independent risk factors for the occurrence of parastomal hernia. CONCLUSIONS: Extraperitoneal colostomy decreased the detectable parastomal hernias but did not reduce the surgical repair rate of parastomal hernias.

The effect of BMI on long-term outcome in patients with rectal cancer and establishment of a nomogram prediction model.

BACKGROUND: The effects of body mass index (BMI) in patients with rectal cancer have been poorly studied and are still controversial. In this study, we aimed to assess the effect of BMI on the long-term outcome in patients with rectal cancer after radical surgery. MATERIALS AND METHODS: Between April 2012 and December 2020, patients who received total mesorectal excision (TME) surgery were enrolled in the study. Patients were divided into four groups according to BMI level. Kaplan-Meier survival curves with log-rank tests were used to analyze overall survival (OS), Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival. Univariate and multivariate analyses were performed to identify the risk factors associated with the long-term outcome. Nomograms were developed to predict the OS and DFS based on independent prognostic factors. RESULTS: A total of 688 patients were included in this study. The median follow-up time was 69 months. The 5-year OS rates of the control, underweight, overweight and obese groups were 79.2%, 62.2%, 88.7% and 86.3%, respectively. The 5-year DFS rates were 74.8%, 58.2%, 80.5% and 81.4%, respectively. Overweight (HR 0.534; 95% CI 0.332-0.860, p = 0.010) was an independent protective factor for OS and DFS (HR 0.675; 95% CI 0.461-0.989, p = 0.044). Underweight was an independent risk factor for DFS (HR = 1.623; 95% CI 1.034-2.548; p = 0.035), and had a trend to be an independent risk factor for OS (HR 1.594; 95% 0.954-2.663; p = 0.075). Nomograms were established to predict the 2-year OS, 5-year OS, 2-year DFS and 5-year DFS with an area under curve (AUC) of 0.767, 0.712, 0.746 and 0.734, respectively. CONCLUSIONS: For rectal cancer patients after radical surgery, overweight was an independent protective factor for OS and DFS. Underweight was an independent risk factor for DFS and had a trend to be an independent risk factor for OS. Nomograms incorporating BMI and other prognostic factors could be helpful to predict long-term outcome.

Methylene blue can increase the number of lymph nodes harvested in colorectal cancer: a meta-analysis.

AIM: The lymph node (LN) status plays an important role in colorectal cancer (CRC), which depends on adequate LN harvest. In some studies, methylene blue has been used to increase the number of LNs harvested in vitro. The purpose was to evaluate the effect of methylene blue staining on LN harvest during radical resection of CRC. METHODS: The Cochrane Library, MEDLINE, Embase, PubMed, and Web of Science were searched from the dates of inception until 15 October 2022. Studies were included if they were randomized controlled trials or nonrandomized controlled trials for radical resection of rectal cancer according to the principle of total mesorectal excision that compared the use of methylene blue with blank control in LN harvest. The primary outcomes were the number of LNs harvested and the incidence of fewer than 12 LNs harvested. RESULT: Of 328 articles found, a meta-analysis was conducted of 15 studies (2 randomized controlled trials and 13 non-randomized controlled trials) composed of 3104 patients. Meta-analysis showed that methylene blue could not only significantly increase the number of LNs harvested in CRC specimens (stained group 28.23 vs unstained group 16.15; weighted mean difference 12.08; 95% CI, 8.03-16.12; p < 0.001; I2 = 95%), but also reduce the incidence of fewer than 12 LNs harvested (methylene blue-stained group 7.91% vs unstained group 30.90%; OR 0.12; 95% CI, 0.05-0.26; p < 0.001; I2 = 78%). CONCLUSION: Methylene blue can increase the number of LNs harvested in CRC, reduce the incidence of fewer than 12 LNs harvested, and ensure the accuracy of LN staging.

Establishment and validation of nomograms for predicting mesorectal lymph node staging and restaging.

BACKGROUND: Preoperative determination of lymph node (LN) status is crucial in treatment planning for rectal cancer. This study prospectively evaluated the risk factors for lymph node metastasis (LNM) at staging and restaging based on a node-by-node pairing between MRI imaging findings and histopathology and constructed nomograms to evaluate its diagnostic value. METHODS: From July 2021 to July 2022, patients with histopathologically verified rectal cancer who underwent MRI before surgery were prospectively enrolled. Histological examination of each LN status in the surgical specimens and anatomical matching with preoperative imaging. Taking histopathological results as the gold standard, federating clinical features from patients and LN imaging features on MRI-T2WI. Risk factors for LN metastasis were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomograms was assessed with calibration plots and bootstrapped-concordance index and validated using validation cohorts. RESULTS: A total of 500 target LNs in 120 patients were successfully matched with node-by-node comparisons. A total of 353 LNs did not receive neoadjuvant therapy and 147 LNs received neoadjuvant chemoradiotherapy (neoCRT). Characterization of LNs not receiving neoadjuvant therapy and multivariate regression showed that the short diameter, preoperative CEA level, mrT-stage, border contour, and signal intensity were associated with a high risk of LN metastasis (P < 0.05). The nomogram predicted that the area under the curve was 0.855 (95% CI, 0.794-0.916) and 0.854 (95% CI, 0.727-0.980) in the training and validation cohorts, respectively. In the neoadjuvant therapy group, short diameter, ymrT-stage, internal signal, and MRI-EMVI were associated with LN positivity (P < 0.05), and the area under the curves using the nomogram was 0.912 (95% CI, 0.856-0.968) and 0.915 (95% CI, 0.817-1.000) in two cohorts. The calibration curves demonstrate good agreement between the predicted and actual probabilities for both the training and validation cohorts. CONCLUSION: Our nomograms combined with preoperative clinical and imaging biomarkers have the potential to improve the prediction of nodal involvement, which can be used as an essential reference for preoperative N staging and restaging of rectal cancer.

Indications and oncological outcomes of selective dissection for clinically suspected lateral lymph node metastasis in patients with rectal cancer based on pretreatment imaging.

BACKGROUND: The aim of this study was to identify the indications and oncological outcomes of selective lateral lymph node dissection (sLLND) in rectal cancer patients. METHODS: A retrospective study was conducted on consecutive patients with rectal cancer who had standard total mesorectal excision and sLLND at our institution. Clinicopathological characteristics and oncological outcomes were analyzed. We performed subgroup analysis and multivariate analysis based on patients with or without preoperative chemoradiotherapy to identify the related risk factors. RESULTS: A total of 77 consecutive patients with TME and sLLND were included. Twenty-two (28.6%) patients with pathological positive lateral lymph nodes metastasis (LLNM) were identified. Forty-seven (61%) patients accepted neoadjuvant chemoradiotherapy (nCRT). The pretreatment maximum short-axis diameters of LLN (≥ 8 mm) were the independent risk factors for LLNM among patients with LLN ≥ 5 mm. Lymph node metastasis were significantly higher in patients with pretreatment LLN ≥ 8 mm than in patients with LLN 5-8 mm (63% vs. 10%, p < 0.001). The receiver operating curve analysis suggested that the optimal cutoff value of LLN short-axis diameter for predicting LLNM was 8 mm. At a median follow-up of 42 months (range 6-140 months) 3 (3.9%) patients with lateral pelvic recurrence were observed. The 3-year cumulative overall survival in patients with LLNM and patients without LLNM was 76.7% and 89.8%, respectively (p = 0.01). The 3-year cumulative disease-free survival was 53.6% in patients with LLNM and 88.3% in patients without LLNM (p = 0.008). CONCLUSION: Patients with LLNM had a worse prognosis. The pretreatment maximum short-axis diameter of LLN (≥ 8 mm) should be considered as an indication for sLLND.

Neoadjuvant Radiotherapy Versus Surgery Alone for Stage II/III Mid-low Rectal Cancer With or Without High-risk Factors: A Prospective Multicenter Stratified Randomized Trial.

OBJECTIVE: The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts. BACKGROUND: NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients. METHODS: According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514). RESULTS: In total, 401 patients were analyzed. With a median 54 months' follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483). CONCLUSIONS AND RELEVANCE: Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.

The effect of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor on patients with rectal cancer.

BACKGROUND: This study aims to determine the real incidence of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor (pPCN) and its prognostic significance in rectal cancer patients. METHODS: Consecutive patients with rectal cancer underwent curative resection between 2015 and 2017 were included. Margin distance was marked and measured in vivo and lymph nodes were harvested on fresh specimens. Clinicopathological characteristics and oncological outcomes (3-year overall survival (OS) and disease-free survival (DFS)) were analyzed between patients with pPCN and patients without pPCN (nPCN). RESULTS: There were 298 patients in the nPCN group and 14 patients (4.5%) in pPCN group. Baseline characteristics were balanced except more patients received preoperative or postoperative chemoradiotherapy in pPCN group. Preoperative more advanced cTNM stage (log-rank p = 0.005) and intraoperative more pericolic lymph nodes beyond 10 cm proximal to the tumor (PCNs) (log-rank p = 0.002) were independent risk factors for pPCN. The maximum short-axis diameter of mesenteric lymph nodes ≥8 mm was also contributed to predicting the pPCN. pPCN was an independent prognostic indicator and associated with worse 3-year OS (66% vs 91%, Cox p = 0.033) and DFS (58% vs 92%, Cox p = 0.012). CONCLUSION: The incidence of pPCN was higher than expected. Patients with high-risk factors (cTNM stage III or more PCNs) might get benefits from an extended proximal bowel resection to avoid residual positive PCNs.

Ligating the rectum with cable tie facilitates rectum transection in laparoscopic anterior resection of rectal cancer.

PURPOSE: Proper transection of the distal rectum is important for reconstruction of bowel continuity in rectal cancer surgery. In this study, we introduced a modified technique for ligation of the distal rectum, and investigated its safety and efficiency to facilitate the rectum transection. METHODS: After complete mobilization and transection of the mesorectum, a cable tie was carefully positioned distal to the tumor, followed by washout and transecting the rectum with a linear stapler. From September 2017 to June 2018, consecutive 67 mid-low rectal cancer patients with laparoscopic anterior resection underwent this technique. Clinical data of these patients, including number of firings, pathological and operative variables, and postoperative outcomes, were compared with those of 132 consecutive patients who underwent traditional surgery from January 2016 to August 2017. RESULTS: Compared with the traditional method, cable tie ligation significantly reduced the number of firings (1.1 ± 0.32 vs. 1.3 ± 0.52, p < 0.001). A very high ratio of one firing transection of rectum was observed in the cable tie group (94.0% vs. 68.9%, p < 0.001), even in patients with tumor at or below the peritoneal reflection (90.2% vs. 54.4%, p < 0.001), in male patients (95.5% vs. 65.8%, p < 0.001), and in obese patients (93.8% vs. 64.9%, p = 0.005). The mean distal margin was longer in the cable tie group (3.19 ± 1.77 cm vs. 2.54 ± 1.36 cm, p = 0.005), with no positive distal margin observed. The operation time, quality of mesorectum, and morbidity between two groups were comparable. Two leaks (3.0%) in the cable tie group were observed, similar to 3.8% in the control. CONCLUSIONS: Ligation of the rectum with a cable tie reduces the number of cartridges, and increases the rate of one stapler firing for rectal transection, even in those difficult cases like male, overweight, and low rectal cancer patients. It is also useful for occlusion of the rectum before washout. It is safe, feasible, and worthwhile for popularization. TRIAL REGISTRATION: Registered at ClinicalTrial.gov, number NCT03570684.

Hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision and central vascular ligation: a novel technique for right colon cancer.

BACKGROUND: It can be difficult to locate the superior mesenteric vein and dissect around middle colic vessels during laparoscopic right hemicolectomy with complete mesocolon excision due to a high rate of vascular variations in the superior mesenteric vessels. Therefore, we report a modified technique for hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision and central vascular ligation, which addresses these two problems. METHODS: Thirty-one consecutive patients with right colon cancer underwent this procedure from March 2014 to August 2015. Extracorporeally, the transverse colon and distal ileum were excised with a transumbilical hand-port incision, and the distal part of the superior mesenteric vein was identified. Intracorporeally, with the assistance of the surgeon's left hand inserted through the incision, D3-lymphadenectomy with central vascular ligation was performed, and the colon with the tumor, which had no blood supply, was removed. Patients' demographic data and intraoperative, postoperative and pathological characteristics were examined. RESULTS: The median operative time was 130.0 (range 115-180) minutes. The median blood loss was 45.0 (range 20-300) milliliters. The median length of the hand-port incision was 7.3 (range 6.0-8.2) centimeters. The median numbers of lymph nodes and central lymph nodes was 34.0 (range 18-91) and 13.0 (range 3-28), respectively. Five (16.1%) of 31 patients had positive central lymph nodes. Specimen morphometric quantitation was as follows: the median distances from the tumor and nearest bowel wall to the high tie were 10.5 (range 5.0-15.0) and 8.0 (range 6.0-12.0) centimeters, respectively; the median resected area of the mesentery was 200.0 (range 96.0-300.0) square centimeters; the median width of the chain of lymph-adipose tissue at the central lymph nodes area was 2.0 (range 0.8-8.0) centimeters; and the median length of the central lymph-adipose chain was 19.0 (range 3.0-26.0) centimeters. CONCLUSIONS: Our procedure confers technical advantages and is feasible for treatment of right colon cancer.

[The Comparison Between Extraction Methods of Exosomes From Ascites of Colorectal Cancer].

OBJECTIVE: To compare the two different methods to isolate the exosome from the ascites of colorectal cancer (CRC) patient and find the efficient one. METHODS: Exosome from the ascites of CRC patient were isolated by two different methods: density gradient exosome isolation (DG-Exo) and Exo-Quick isolation, and followed by identification with transmission electron microscopy observation and Western blot analysis. And then, Nanodrop was used for protein quantification. RESULTS: Exosome were isolated by both of the two methods. The protein concentration of the exosome isolated by the Exo-Quick isolation were higher than that of DG-Exo. CONCLUSION: Exo-Quick isolation can obtain higher purity and more complete exosome from the ascites.

Head-to-head comparison of the diagnostic performance between 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer: a systematic review and meta-analysis.

This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.

T2WI-based texture analysis predicts preoperative lymph node metastasis of rectal cancer.

BACKGROUND: To prospectively develop and validate the T2WI texture analysis model based on a node-by-node comparison for improving the diagnostic accuracy of lymph node metastasis (LNM) in rectal cancer. METHODS: A total of 381 histopathologically confirmed lymph nodes (LNs) were collected. LNs texture features were extracted from MRI-T2WI. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection to construct the LN rad-score. Then the clinical risk factors and LN texture features were combined to establish combined predictive model. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Decision curve analysis (DCA) and nomogram were used to evaluate the clinical application of the model. RESULTS: A total of 107 texture features were extracted from LN-MRI images. After selection and dimensionality reduction, the radiomics prediction model consisting of 8 texture features showed well-predictive performance in the training and validation cohorts (AUC, 0.676; 95% CI 0.582-0.771) (AUC, 0.774; 95% CI 0.648-0.899). A clinical-radiomics prediction model with the best performance was created by combining clinical and radiomics features, 0.818 (95% CI 0.742-0.893) for the training and 0.922 (95% CI 0.863-0.980) for the validation cohort. The LN Rad-score in clinical-radiomics nomogram obtained the highest classification contribution and was well calibrated. DCA demonstrated the superiority of the clinical-radiomics model. CONCLUSION: The lymph node T2WI-based texture features can help to improve the preoperative prediction of LNM.

Reactive oxygen species in colorectal cancer adjuvant therapies.

Colorectal cancer (CRC), a prevalent global malignancy, often necessitates adjuvant therapies such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy to mitigate tumor burden in advanced stages. The efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). Previous research underscores the pivotal role of ROS in gut pathology, targeted therapy, and drug resistance. ROS-mediated CRC adjuvant therapies encompass a myriad of mechanisms, including cell death and proliferation, survival and cell cycle, DNA damage, metabolic reprogramming, and angiogenesis. Preliminary clinical trials have begun to unveil the potential of ROS-manipulating therapy in enhancing CRC adjuvant therapies. This review aims to provide a comprehensive synthesis of studies exploring the role of ROS in CRC adjuvant therapies.

Do treated rectal tumors appear differently on MRI after chemotherapy versus chemoradiotherapy?

PURPOSE: Increasing studies have focused on neoadjuvant chemotherapy (NCT) in rectal cancer. However, few studies explored the differences in radiographic variation between patients treated with NCT and neoadjuvant chemoradiotherapy (NCRT). METHODS: Stage II/III rectal cancer patients from March 2016 to December 2019 meeting the criteria treated with NCRT or NCT were included. MRI features, including tumor location, longitudinal length, DWI signal, MRI tumor regression grade (mrTRG), and radiomic texture features, before and after neoadjuvant treatments were reviewed. RESULTS: 116 patients with NCRT and 61 with NCT were analyzed. Among these patients, 46 patients in the NCRT group and 18 in the NCT group were responders with pathological TRG0-1. Within these responders, the mean tumor longitudinal length regression rate (TLRR) of the NCT group was 60.08 ± 11.17%, which was significantly higher than the 50.73 ± 15.28% of the NCRT group (p = 0.010). The proportion of high signal in the DWI image after NCT was higher than that of the NCRT group (88.89% vs 50.00%, p = 0.004). NCT responders had significantly higher median change rates than those of NCRT responders in 11 radiomic features, especially those shape features. CONCLUSION: MRI images change differently between responders treated with NCRT and those with NCT in rectal cancer. The tumor volumetry and some radiomic features change more obviously in NCT responders, and the tumor signal changes more obviously in NCRT responders. During the evaluation of the response of the tumor to the neoadjuvant treatments, images of patients should be treated differently.

Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma.

INTRODUCTION: Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis. OBJECTIVES: Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC). METHODS: Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), ß-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings in vitro. RESULTS: We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both in silico and in vitro. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness. CONCLUSION: Our findings provide insights into the role of SRGs in patients stratification and precision medicine.

Global Status of Research on Lateral Lymph Nodes in Rectal Cancer from 1994 to 2022: A Bibliometric Analysis.

Tremendous progress has been made in the field of lateral lymph nodes (LLNs) in rectal cancer, but no bibliometric analysis in this field has been carried out and published. To reveal the current status and trends in LLNs in rectal cancer, this bibliometric analysis was performed. Cooperation network, co-citation and keyword co-occurrence analyses were conducted. Annual publication, cooperation relationships among authors, institutions and countries, co-cited journal, co-cited author, co-cited reference and keywords were the main outcomes. A total of 345 studies were included in this bibliometric analysis. The number of articles published in this field has been increasing year by year. The authors, institutions and countries worked closely together in this field. Japan has the largest number of published articles, accounting for 51.59% of the total publications. International Journal of Colorectal Disease (30 papers, 8.70%) published the most papers in this field. The JCOG0212 trial was the most cited article. Preoperative chemoradiotherapy, multicenter, lateral lymph node dissection (LLND) and metastasis are recent hot keywords, and LLND had the highest burst strength. In conclusion, this bibliometric analysis found that Japanese institutions and authors dominated the field of LLNs in rectal cancer. The JCOG0212 trial was the most influential article, which had a significant impact on the development of guidelines. LLND is a hotspot in this field with the highest burst strength. Further prospective studies are needed in this field.

Ferroptosis regulation by methylation in cancer.

Epigenetic regulation plays a critical role in cancer development and progression. Methylation is an important epigenetic modification that influences gene expression by adding a methyl group to nucleic acids and proteins. Ferroptosis is a new form of regulated cell death triggered by the accumulation of iron and lipid peroxidation. Emerging evidence have shown that methylation regulation plays a significant role in the regulation of ferroptosis in cancer. This review aims to explore the methylation regulation of ferroptosis in cancer, including reactive oxygen species and iron bio-logical activity, amino acid and lipid metabolism, and drugs interaction. The findings of this review may provide new insights and strategies for the prevention and treatment of cancer.