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Chen X, Zhong M, Chen C, Huang L, Zhang K, Wu X. Multivariable prediction of returning to work among early-onset colorectal cancer survivors in China: A two-year follow-up. Asia Pac J Oncol Nurs 2025; 12:100637. [PMID: 39990168 PMCID: PMC11843046 DOI: 10.1016/j.apjon.2024.100637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/04/2024] [Indexed: 02/25/2025] Open
Abstract
Objective The number of early-onset colorectal cancer survivors (EOCRCs) is increasing. The primary aim of rehabilitation after battling cancer is to enable patients to return to work, as they constitute a significant contributor to societal productivity. A predictive model was developed to identify priority populations requiring intervention and refine responses to increase their capacity to return to work after undergoing treatment for EOCRC. Methods The baseline information was collected before patients were discharged at the end of their treatment course. The data of patients who returned to work were collected at 1 and 2 years after discharge. A predictive variable model was developed via binary logistic regression. The TRIPOD checklist was used. Results At 1 year, 64.7% of the EOCRC survivors had returned to work. Male sex, education, return to work self efficacy, re-entry readiness and social support increased the possibility of returning to work; higher levels of self-perceived fatigue and lower levels of family care decreased the possibility of returning to work within the 1-year model. At 2 years, 72.8% of the EOCRC survivors had returned to work. In the 2-year model, education, self-transcendence, return to work self efficacy, re-entry readiness and occupational environment increased the possibility of returning to work; self-perceived fatigue and psychosocial adjustment decreased the possibility of returning to work. Conclusions The results of this study can guide early assessment and intervention for EOCRC survivors, to facilitate their return to work.
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Affiliation(s)
- Xiaojun Chen
- School of Economics and Management, Beijing University of Posts and Telecommunications, Institution I, Beijing, China
- Band of Guiyang Co., Ltd, Institution II, Guiyang, China
| | - Mengjiao Zhong
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Institution III, Guangzhou, China
| | - Chunyan Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Institution III, Guangzhou, China
| | - Lingyao Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Institution III, Guangzhou, China
| | - Kun Zhang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Institution IV, Shandong, China
| | - Xiaodan Wu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Institution III, Guangzhou, China
- Unit of Psychiatry, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Institution V, Macao SAR, China
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Xu W, Li W, Kuai D, Li Y, Sun W, Liu X, Xu B. Identification of endoplasmic reticulum stress-related genes as prognostic markers in colon cancer. Cancer Biol Ther 2025; 26:2458820. [PMID: 40169935 PMCID: PMC11970746 DOI: 10.1080/15384047.2025.2458820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 12/20/2024] [Accepted: 01/22/2025] [Indexed: 04/03/2025] Open
Abstract
Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved in ERS that could serve as prognostic markers in colon cancer remain underexplored. This study aims to identify and validate endoplasmic reticulum stress related genes (ERSRGs) in colon cancer that correlate with patient prognosis, thereby enhancing the understanding of ERS in oncological outcomes and potential therapeutic targeting. We utilized bioinformatics analyses to identify ERSRGs from publicly available colon cancer datasets. Differential expression analysis and survival analysis were performed to assess the prognostic significance of these genes. Validation was conducted through quantitative real-time PCR (RT-qPCR) on selected colon cancer cell lines. Our study identified nine ERS related genes (ASNS, ATF4, ATF6B, BOK, CLU, DDIT3, MANF, SLC39A14, TRAF2) involved in critical pathways including IL-12, PI3K-AKT, IL-7, and IL-23 signaling, and linked to 1-, 3-, and 5-year survival of patients with colon cancer. A multivariate Cox model based on these ERS related genes demonstrated significant prognostic power. Further, TRAF2 strong correlated with immune cells infiltration, suggesting its potential roles in modulating immune responses in the tumor microenvironment. The RT-qPCR validation confirmed the differential expression of these genes in human colon cancer cell lines versus human normal colonic epithelial cell line. The identified ERSRGs could serve as valuable prognostic markers and may offer new insights into the therapeutic targeting of ERS in colon cancer.
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Affiliation(s)
- Wenjing Xu
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Wei Li
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Dayu Kuai
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Yaqiang Li
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Wei Sun
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Xian Liu
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
| | - Baohong Xu
- Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China
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Li WB, Li J, Yu W, Gao JH. Short-term efficacy of laparoscopic radical resection for colorectal cancer and risk of unplanned reoperation after surgery. World J Gastrointest Surg 2025; 17:102442. [DOI: 10.4240/wjgs.v17.i4.102442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/11/2025] [Accepted: 03/07/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Surgery is the first choice of treatment for patients with colorectal cancer. Traditional open surgery imparts great damage to the body of the patient and can easily cause adverse stress reactions. With the continuous development of medical technology, laparoscopic minimally invasive surgery has shown great advantages for the treatment of patients with celiac disease.
AIM To investigate the short-term efficacy of laparoscopic radical surgery and traditional laparotomy for the treatment of colorectal cancer, and the differences in the risk analysis of unplanned reoperation after operation.
METHODS As the research subjects, this study selected 100 patients with colorectal cancer who received surgical treatment at the Yulin First Hospital from January 2018 to January 2022. Among them, 50 patients who underwent laparoscopic radical resection were selected as the research group and 50 patients who underwent traditional laparotomy were selected as the control group. Data pertaining to clinical indexes, gastrointestinal hormones, nutrition indexes, the levels of inflammatory factors, quality of life, Visual Analog Scale score, and the postoperative complications of the two groups of patients before and after treatment were collected, and the therapeutic effects in the two groups were analyzed and compared.
RESULTS Compared with the control group, perioperative bleeding, peristalsis recovery time, and hospital stays were significantly shorter in the research group. After surgery, the levels of gastrin (GAS) and motilin (MTL) were decreased in both groups, and the fluctuation range of GAS and MTL observed in the research group was significantly lower than that recorded in the control group. The hemoglobin (Hb) levels increased after surgery, and the level of Hb in the research group was significantly higher compared with the control group. After the operation, the expression levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein and the total incidence of complications were significantly lower in the research group compared with the control group. One year after the operation, the quality of life of the two groups was greatly improved, with the quality of life in the research group being significantly better.
CONCLUSION Laparoscopy was effective for colorectal surgery by reducing the occurrence of complications and inflammatory stress reaction; moreover, the quality of life of patients was significantly improved, which warrants further promotion.
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Affiliation(s)
- Wen-Bin Li
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Jiang Li
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Wei Yu
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Jian-Hua Gao
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
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Zheng ZP, Zhang YG, Long MB, Ji KQ, Peng JY, He K. Construction of a risk prediction model for postoperative cognitive dysfunction in colorectal cancer patients. World J Gastrointest Surg 2025; 17:104459. [DOI: 10.4240/wjgs.v17.i4.104459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/06/2025] [Accepted: 02/24/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most prevalent and lethal malignant tumors worldwide. Currently, surgical intervention was the primary treatment modality for CRC. However, increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction (POCD).
AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine (DEX).
METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024. Patients were allocated into a modeling group (n = 98) and a validation group (n = 42) in a 7:3 ratio. General clinical data were collected. Additionally, in the modeling group, patients who received DEX preoperatively were incorporated into the observation group (n = 54), while those who did not were placed in the control group (n = 44). The incidence of POCD was recorded for both cohorts. Data analysis was performed using statistical product and service solutions 20.0, with t-tests or χ2 tests employed for group comparisons based on the data type. Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables. Multivariate analysis was carried out using Logistic regression. Based on the identified risk factors, a risk prediction model for POCD in CRC patients was developed, and the predictive value of these risk factors was evaluated.
RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status, alcohol consumption, years of education, anesthesia duration, intraoperative blood loss, intraoperative hypoxemia, use of DEX during surgery, intraoperative use of vasoactive drugs, surgical time, systemic inflammatory response syndrome (SIRS) score (P < 0.05). Multivariate Logistic regression analysis identified that diabetes [odds ratio (OR) = 4.679, 95% confidence interval (CI) = 1.382-15.833], alcohol consumption (OR = 5.058, 95%CI: 1.255-20.380), intraoperative hypoxemia (OR = 4.697, 95%CI: 1.380-15.991), no use of DEX during surgery (OR = 3.931, 95%CI: 1.383-11.175), surgery duration ≥ 90 minutes (OR = 4.894, 95%CI: 1.377-17.394), and a SIRS score ≥ 3 (OR = 4.133, 95%CI: 1.323-12.907) were independent risk factors for POCD in CRC patients (P < 0.05). A risk prediction model for POCD was constructed using diabetes, alcohol consumption, intraoperative hypoxemia, non-use of DEX during surgery, surgery duration, and SIRS score as factors. A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity (88.56%), specificity (70.64%), and area under the curve (AUC) (AUC = 0.852, 95%CI: 0.773-0.919). The model was validated using 42 CRC patients who met the inclusion criteria, demonstrating sensitivity (80.77%), specificity (81.25%), and accuracy (80.95%), and AUC (0.805) in diagnosing cognitive impairment, with a 95%CI: 0.635-0.896.
CONCLUSION Logistic regression analysis identified that diabetes, alcohol consumption, intraoperative hypoxemia, non-use of DEX during surgery, surgery duration, and SIRS score vigorously influenced the occurrence of POCD. The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals. This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.
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Affiliation(s)
- Zhen-Ping Zheng
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
| | - Yong-Guo Zhang
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
| | - Ming-Bo Long
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
| | - Kui-Quan Ji
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
| | - Jin-Yan Peng
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
| | - Kai He
- Department of Anesthesiology, The People’s Hospital of Qian Nan, Duyun 558000, Guizhou Province, China
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Tang QY, Yu W. Logistic regression analysis of pathological features of bone metastasis in colorectal cancer and related influencing factors after surgery. World J Gastrointest Surg 2025; 17:100851. [DOI: 10.4240/wjgs.v17.i4.100851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/23/2025] [Accepted: 02/18/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignant tumor in the digestive system, whose main treatment comprises surgical resection, radiotherapy and chemotherapy, and targeted drug therapy. At present, the radical resection of CRC is the main way of achieving an early cure.
AIM To investigate the logistic regression analysis of bone metastasis after CRC surgery and related influencing factors.
METHODS We selected 100 patients who underwent surgery for CRC and were admitted from February 2018 to February 2024, collected the general data of bone metastasis, and collected the pathological characteristics of patients with bone metastasis. Next, we divided them into groups with and without bone metastasis (Bone metastases group, n = 44; no bone metastases group, n = 56), compared the clinical data of the two groups, and analyzed the risk factors of bone metastasis using logistic regression analysis.
RESULTS Among the 100 patients, the mean age was 54.33 ± 8.45 years, and most were male (54.55%). The proportion of patients with lytic bone changes was 43.18%. The most common location of combined bone metastasis was the pelvis, whereas only 5 patients had limb transfer. There was a higher incidence of lung than of pancreatic or liver metastases. Regression analysis showed that the primary location of the cancer was rectal cancer. Lymph node involvement, lung metastasis, and no postoperative chemotherapy were the risk factors for postoperative bone metastasis in patients who underwent surgery for CRC (P < 0.05).
CONCLUSION Rectal cancer, lymph node involvement, complicated pulmonary metastasis, and no postoperative chemotherapy treatment can help predict high risk of bone metastasis in CRC.
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Affiliation(s)
- Qiu-Yan Tang
- The First Department of Oncology, Jiujiang First People’s Hospital, Jiujiang 332000, Jiangxi Province, China
| | - Wei Yu
- Department of Orthopedics, Jiujiang First People’s Hospital, Jiujiang 332000, Jiangxi Province, China
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Lu XF, Zhang HW, Chang X, Guo YZ. F-box protein 22: A prognostic biomarker for colon cancer associated with immune infiltration and chemotherapy resistance. World J Gastrointest Oncol 2025; 17:102913. [DOI: 10.4251/wjgo.v17.i4.102913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/10/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system, characterized by a high incidence rate and substantial disease burden. The F-box protein 22 (FBXO22) plays a role in forming a specific type of ubiquitin ligase subunit, which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer. Nevertheless, the function of FBXO22 in the context of colon cancer remains inadequately elucidated.
AIM To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.
METHODS Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered, along with pertinent clinical data. Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immunohistochemistry. The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues, and the relationship between these expression levels and various pathologic characteristics of patients, such as age, sex, and clinical stage, was analyzed. Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups: A blank control group, a negative control group, and a si-FBXO22 group. FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting. The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay, while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays. Various online platforms, including the Timer Immune Estimation Resource, were used to analyze pan-cancer expression, promoter methylation levels, and mutation frequencies of the FBXO22 gene in colon cancer patients. Additionally, the correlation between FBXO22 gene expression, patient prognosis, immune cell infiltration, and the expression of immune molecules in the colon cancer microenvironment was investigated. The relationship between FBXO22 gene expression and chemotherapy resistance, along with the potential mechanisms of action of the FBXO22 gene, were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.
RESULTS Compared with normal colonic tissues, the FBXO22 gene was highly expressed in colon cancer tissues. Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents. FBXO22 expression suppresses the infiltration of anti-tumor immune cells. In vitro, FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.
CONCLUSION The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.
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Affiliation(s)
- Xiao-Fei Lu
- Department of Clinical Medicine, Hebei University of Engineering, Handan 056002, Hebei Province, China
| | - Hong-Wei Zhang
- Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan 056002, Hebei Province, China
| | - Xiao Chang
- Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan 056002, Hebei Province, China
| | - Yong-Ze Guo
- Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan 056002, Hebei Province, China
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Skalny AV, Kushlinskii NE, Korobeinikova TV, Alferov AA, Kuzmin YB, Kochkina SO, Gordeev SS, Mammadli ZZ, Stilidi IS, Tinkov AA. Zinc, copper, copper-to-zinc ratio, and other biometals in blood serum and tumor tissue of patients with colorectal cancer. Biometals 2025; 38:529-544. [PMID: 39820949 DOI: 10.1007/s10534-024-00660-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/24/2024] [Indexed: 01/19/2025]
Abstract
The objective of the present study was to assess serum and cancerous tissue biometal levels in colorectal cancer (CRC) patients, and its relation to disease severity. A total of 90 CRC patients and 97 controls were involved in the present study. The level of biometals in blood serum and colon tissues (only in CRC cases) was evaluated by inductively-coupled plasma mass-spectrometry. CRC patients are characterized by lower serum Ca, Fe, Se, and Zn, as well as higher serum Co, Cu, Mg, V, and Cu/Zn ratio compared to healthy controls. The lowest serum Zn levels and the highest Cu concentration and Cu/Zn ratio were observed in patients with the largest tumor size. Regression analysis demonstrated that tumor size is a significant negative predictor of serum Se levels, being positively associated with serum Cu/Zn values. The degree of metastasis to regional lymph nodes was inversely associated with circulating Ca, Co, Mg, Zn, and Mn levels. Serum Mg and Mn levels were positively associated with the stage of the disease and tumor location, respectively. Cancerous tissue Ca and Mo levels were lower, while Mg content was higher compared to healthy adjacent tissues. In cancerous tissues a constant but non-significant trend to elevation of tissue Zn content with increasing tumor size was observed. In addition, serum Cu, Zn, and Cu/Zn values positively correlated with the respective tumor values. These findings demonstrate that altered biometal metabolism is associated with CRC, while systemic Cu/Zn ratio may be indicative of Cu and Zn imbalance in cancerous tissue.
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Affiliation(s)
- Anatoly V Skalny
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia
| | | | - Tatiana V Korobeinikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia
| | - Aleksandr A Alferov
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
- Russian University of Medicine, Moscow, 127473, Russia
| | | | - Sofya O Kochkina
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Sergey S Gordeev
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Zaman Z Mammadli
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Ivan S Stilidi
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, 115478, Russia
| | - Alexey A Tinkov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia.
- Peoples Friendship University of Russia (RUDN University), Moscow, 117198, Russia.
- P.G. Demidov Yaroslavl State University, Yaroslavl, 150003, Russia.
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Hai ZX, Zhao JN, Liu XR, Qu SP, Lv Q, Wang CY. Effects of Planned Stoma Before Neoadjuvant Chemoradiation in Patients With Endoscopically Obstructing Colorectal Cancer. Am Surg 2025:31348251329482. [PMID: 40114325 DOI: 10.1177/00031348251329482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
PurposeIn order to investigate whether colorectal cancer (CRC) patients with endoscopic obstruction benefited from a planned stoma before neoadjuvant chemoradiation (nCRT).MethodsPatients who were diagnosed with CRC with endoscopic obstruction at a single clinical center from January 2017 to April 2022 were retrospectively collected. Baseline characteristics and short-term and long-term outcomes were compared between the stoma group and the no stoma group. Statistical analysis was performed using SPSS (version 22.0) software.ResultsA total of 51 CRC patients with endoscopic obstruction were included in this study. Eleven (21.6%) patients received a planned stoma before nCRT, and 40 (78.4%) patients were treated with immediate nCRT. The mean time from diagnosis to nCRT was 30.6 days for the stoma group and 11.9 days for the no stoma group. There was a significant delay in the initiation of nCRT in the stoma group (P < 0.05). In terms of complications, there was a statistical difference between the stoma group and the no stoma group (P < 0.05). Planned stoma before nCRT did not affect survival for patients with endoscopically obstructing CRC (P > 0.05).ConclusionA planned stoma caused delay in nCRT; the no stoma group was more likely to develop perforation or obstruction of the tumor during nCRT. A comprehensive assessment might be needed to determine whether a planned stoma was necessary in CRC patients with endoscopic obstruction.
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Affiliation(s)
- Zhan-Xiang Hai
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jun-Nan Zhao
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xu-Rui Liu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shu-Pei Qu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Quan Lv
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chun-Yi Wang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Ni J, Wan CG, Sui ZQ. Efficacy and safety of radiotherapy in patients with microsatellite stable or proficient mismatch repair colorectal cancer liver metastasis. World J Gastrointest Oncol 2025; 17:102873. [PMID: 40092939 PMCID: PMC11866244 DOI: 10.4251/wjgo.v17.i3.102873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/05/2024] [Accepted: 01/14/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally, and the occurrence of liver metastasis significantly affects patient survival prognosis. In recent years, the application of immune checkpoint inhibitors (ICIs) in cancer treatment has made important progress, especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency. However, for the majority of patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) colorectal cancer, the efficacy of ICIs is limited, prompting researchers to explore combination therapy strategies to improve efficacy. Targeted drugs such as tyrosine kinase inhibitors (TKIs) and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation. AIM To investigate the efficacy and safety of the combination therapy of radiotherapy, ICIs, and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis (CCLM), in order to provide new clinical treatment references. METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024. Based on the treatment interventions received, the patients were divided into a control group (n = 21, receiving ICIs and TKIs combination therapy) and an observation group (n = 22, receiving radiotherapy, ICIs, and TKIs triple therapy). The therapeutic effects, serum tumor markers (carcinoembryonic antigen and carbohydrate antigen 199), survival status, and adverse reactions were compared between the two groups. RESULTS The disease control rate in the observation group (63.64%) was significantly higher than that of the control group (23.81%) (P < 0.05). Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment, with the observation group demonstrating a more significant change (P < 0.05). The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months, respectively, while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months, respectively. The control group had longer survival times than the observation group, but the differences were not statistically significant (P > 0.05). The incidence of adverse reactions, including nausea and vomiting, gastrointestinal reactions, skin reactions, bone marrow suppression, liver and kidney function impairment, neurotoxicity, leukopenia, neutropenia, and thrombocytopenia, showed no significant differences between the two groups (P > 0.05). CONCLUSION Compared to the ICIs and TKIs combination therapy, the radiotherapy, ICIs, and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions, making it a treatment regimen worthy of further validation.
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Affiliation(s)
- Jie Ni
- Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou 311100, Zhejiang Province, China
| | - Chu-Gen Wan
- Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou 311100, Zhejiang Province, China
| | - Zi-Qi Sui
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
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Qin K, Luo JY, Zeng DT, Huang WY, Li B, Li Q, Zhan YT, He RQ, Huang WJ, Chen G, Chen ZY, Chi BT, Tang YX, Tang RX, Li H. Kinesin family member 14 expression and its clinical implications in colorectal cancer. World J Gastrointest Oncol 2025; 17:102696. [PMID: 40092935 PMCID: PMC11866231 DOI: 10.4251/wjgo.v17.i3.102696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/22/2024] [Accepted: 12/25/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer globally, causing over 900000 deaths annually. Risk factors include aging, diet, obesity, sedentary lifestyle, tobacco use, genetic predisposition, and inflammatory bowel disease. Despite current treatments, survival rates for advanced CRC remain low, highlighting the need for better therapeutic strategies. AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14 (KIF14) expression within CRC specimens. Additionally, this study aims to investigate the interaction between nitidine chloride (NC) and KIF14, considering their potential as therapeutic targets. METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining. The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference (SMD) for KIF14 mRNA levels. The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves, along with measures of sensitivity, specificity, and likelihood ratios. Additionally, clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC. Survival analysis established the prognostic value of KIF14 in CRC. The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis, and molecular docking was utilized to explore the targeting affinity between NC and KIF14. RESULTS KIF14 was highly expressed in 208 CRC patients. Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples, with an SMD of 1.92 (95%CI: 1.49-2.35). The area under the curve was 0.94 (95%CI: 0.92-0.96), with a sensitivity of 0.85 (95%CI: 0.78-0.90) and a specificity of 0.90 (95%CI: 0.85-0.93). The positive and negative likelihood ratios were 8.38 (95%CI: 5.39-13.02) and 0.17 (95%CI: 0.11-0.26), respectively. At the single-cell level, significant overexpression of KIF14 was observed in CRC cells (P < 0.001), with 35 CRC cell lines dependent on KIF14 for growth. The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets (P < 0.05). Binding energy calculations indicated that KIF14 is a potential target for NC (binding energy: 10.3 kcal/mol). CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor, potentially serving as a therapeutic target for NC in the treatment of CRC.
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Affiliation(s)
- Kai Qin
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jia-Yuan Luo
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Da-Tong Zeng
- Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
| | - Wan-Ying Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bin Li
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qi Li
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Ting Zhan
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei-Jian Huang
- Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zu-Yuan Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bang-Teng Chi
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Xing Tang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Rui-Xue Tang
- Department of Pathology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250000, Shandong Province, China
| | - Hui Li
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Wei L, Wang L, Liu YG, Gao LF. Expression significance of biomarker MORC4 in colorectal cancer patients and its relationship with pathological features and prognosis. World J Gastrointest Oncol 2025; 17:102434. [PMID: 40092938 PMCID: PMC11866243 DOI: 10.4251/wjgo.v17.i3.102434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/08/2024] [Accepted: 01/10/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignant gastrointestinal tumors worldwide, with high incidence and mortality rates. AIM To investigate the expression significance of the chromatin-remodeling protein MORC family CW-type zinc finger 4 (MORC4) as a biomarker in CRC patients, and to explore its relationship with pathological features and prognosis. METHODS A total of 143 CRC specimens and 57 adjacent tissue specimens, surgically removed from our hospital between January 2020 and January 2021, were collected. MORC4 protein expression was assessed using immunohistochemistry after paraffin embedding. The relationship between MORC4 protein expression and clinicopathological characteristics of patients was analyzed. Kaplan-Meier survival curves were plotted to analyze the relationship between MORC4 protein expression and prognosis in CRC patients. RESULTS Compared with adjacent tissues, the expression rate of MORC4 protein in CRC tissues was significantly higher (P < 0.05). No significant difference was observed in the high expression rate of MORC4 protein in CRC tissues among patients of different gender, age, tumor location, tumor diameter, and primary tumor status (P > 0.05). However, significant differences were found in the high expression rate of MORC4 protein in patients with different degrees of differentiation, lymph node metastasis, distant metastasis, tumor-lymph node-metastasis stage, and serum carcinoembryonic antigen levels (P < 0.05). Compared with patients with low MORC4 expression, patients with high MORC4 expression had a worse prognosis (P < 0.05). CONCLUSION The upregulation of MORC4 expression in CRC patients is closely related to disease severity and prognosis, suggesting its potential as an evaluation biomarker, which warrants further investigation.
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Affiliation(s)
- Li Wei
- Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Liang Wang
- Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Ya-Gang Liu
- Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Li-Fei Gao
- Department of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
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Shahzad M, Hameed H, Amjad A, Khan MA, Qureshi IS, Hameed A, Saeed A, Munir R. An updated landscape on nanopharmaceutical delivery for mitigation of colon cancer. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:2107-2125. [PMID: 39361171 DOI: 10.1007/s00210-024-03482-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 09/21/2024] [Indexed: 03/19/2025]
Abstract
Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.
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Affiliation(s)
- Maria Shahzad
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Huma Hameed
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan.
| | - Ayesha Amjad
- Faculty of Food Technology and Nutrition Sciences, Lahore University of Biological and Applied Sciences, Lahore, 54000, Pakistan
| | - Mahtab Ahmad Khan
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Inaba Shujaat Qureshi
- Department of Human Nutrition and Dietetics, Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Gulberg III, Lahore, 54000, Pakistan
| | - Anam Hameed
- Department of Human Nutrition and Dietetics, Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Gulberg III, Lahore, 54000, Pakistan
| | - Asad Saeed
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Rabia Munir
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan
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Wang Y, Hu C, Du T, Li J, Hui K, Jiang X. Combination of potassium oxonate with anti-PD-1 for the treatment of colorectal cancer. Front Oncol 2025; 15:1528004. [PMID: 39990679 PMCID: PMC11842225 DOI: 10.3389/fonc.2025.1528004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/20/2025] [Indexed: 02/25/2025] Open
Abstract
Introduction Identification of effective therapies for colorectal cancer (CRC) remains an urgent medical need, especially for the microsatellite stable (MSS) phenotype. In our previous study, potassium oxonate (PO), a uricase inhibitor commonly used for elevating uric acid in mice, unexpectedly showed remarkable inhibition of tumor growth when combined with anti-programmed death-1 (PD-1). Further research demonstrated that the combination of potassium oxonate and anti-PD-1 could reprogram the immune microenvironment. This study aimed to explore the anti-tumor effect of PO combined with anti-PD-1, and investigate the impact on the immunosuppressive tumor microenvironment (TME). Methods We established a syngeneic mouse model of CRC and divided into groups of control group, single drugs group of PO and anti-PD-1, and the combination group. Use the HE staining, immunohistochemistry (IHC) and TUNEL staining of tumor issues to verify the anti-neoplasm of each group. We also tested the changes of TME through flow cytometry of spleen of mice in each group, as well as the IHC of cytokines. Results The co-therapy of PO and anti-PD-1 showed admirable anti-tumor effect compared with the control group and the single drug groups. The TME were tended to an environment beneficial for killing tumors by enhancing chemotactic factor release, increasing CD8+ T cell infiltration and activation, and decreasing the amount of regulatory T cells. Moreover, IFN-γ and IL-2 secretion were found to be enriched in the tumor TME. Conclusion Our study indicated that combination of PO and anti-PD-1 could synergistically suppress CRC progression and altered the tumor microenvironment in favor of antitumor immune responses.
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Affiliation(s)
- Yuanyuan Wang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Chenxi Hu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Tianpeng Du
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiawen Li
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Kaiyuan Hui
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
| | - Xiaodong Jiang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China
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Gorría T, Sierra-Boada M, Rojas M, Figueras C, Marin S, Madurga S, Cascante M, Maurel J. Metabolic Singularities in Microsatellite-Stable Colorectal Cancer: Identifying Key Players in Immunosuppression to Improve the Immunotherapy Response. Cancers (Basel) 2025; 17:498. [PMID: 39941865 PMCID: PMC11815897 DOI: 10.3390/cancers17030498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
Although immune checkpoint inhibitor (ICI) therapy is currently the standard of care in microsatellite-unstable (MSI) metastatic colorectal cancer (CRC), ICI therapy, alone or in combination with other therapies, is not a treatment approach in microsatellite-stable (MSS) CRC, which is present in 95% of patients. In this review, we focus on metabolic singularities-at the transcriptomic (either bulk or single cell), proteomic, and post-translational modification levels-that induce immunosuppression in cancer and specifically in MSS CRC. First, we evaluate the current efficacy of ICIs in limited and metastatic disease in MSS CRC. Second, we discuss the latest findings on the potential biomarkers for evaluating ICI efficacy in MSS CRC using strict REMARK criteria. Third, we review the current evidence on metabolic patterns in CRC tumors and immune cell metabolism to advance our understanding of metabolic crosstalk and to pave the way for the development of combination strategies to enhance ICI efficacy.
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Affiliation(s)
- Teresa Gorría
- Medical Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (T.G.); (M.R.); (C.F.)
- Translational Genomics and Targeted Therapies in Solid Tumors, Agustí Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain
- Medicine Department, University of Barcelona, 08036 Barcelona, Spain
| | - Marina Sierra-Boada
- Medical Oncology Department, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08208 Sabadell, Spain;
| | - Mariam Rojas
- Medical Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (T.G.); (M.R.); (C.F.)
| | - Carolina Figueras
- Medical Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (T.G.); (M.R.); (C.F.)
| | - Silvia Marin
- Department of Biochemistry and Molecular Biomedicine, University of Barcelona, 08036 Barcelona, Spain;
- Institute of Biomedicine of University of Barcelona (IBUB), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Sergio Madurga
- Department of Material Science and Physical Chemistry, Research Institute of Theoretical and Computational Chemistry (IQTCUB), University of Barcelona, 08028 Barcelona, Spain;
| | - Marta Cascante
- Department of Biochemistry and Molecular Biomedicine, University of Barcelona, 08036 Barcelona, Spain;
- Institute of Biomedicine of University of Barcelona (IBUB), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
| | - Joan Maurel
- Medical Oncology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain; (T.G.); (M.R.); (C.F.)
- Translational Genomics and Targeted Therapies in Solid Tumors, Agustí Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain
- Medicine Department, University of Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
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Wang C, Guo J, Zhang Y, Zhou S, Jiang B. Cuproptosis-Related Gene FDX1 Suppresses the Growth and Progression of Colorectal Cancer by Retarding EMT Progress. Biochem Genet 2025; 63:775-788. [PMID: 38520567 PMCID: PMC11832605 DOI: 10.1007/s10528-024-10784-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 01/28/2024] [Indexed: 03/25/2024]
Abstract
Colorectal cancer (CRC) is a usual cancer and a kind of lethiferous cancer. Cuproptosis-related gene ferredoxin 1 (FDX1) has been discovered to act as a suppressor, thereby suppressing some cancers' progression. But, the regulatory functions of FDX1 in CRC progression keep vague. In this work, at first, through TCGA database, it was revealed that FDX1 exhibited lower expression in COAD (colon adenocarcinoma) tissues, and CRC patients with lower FDX1 expression had worse prognosis. Furthermore, FDX1 expression was verified to be down-regulated in CRC tissues (n = 30) and cells. It was further uncovered that FDX1 expression was positively correlated with CDH1 and TJP1 (epithelial marker), and negatively correlated with CDH2, TWIST1, and FN1 (stromal marker), suggesting that FDX1 was closely associated with the epithelial-mesenchymal transition (EMT) progress. Next, it was demonstrated that overexpression of FDX1 suppressed cell viability, invasion, and migration in CRC. Furthermore, it was verified that FDX1 retarded the EMT progress in CRC. Lastly, through rescue assays, the inhibited CRC progression mediated by FDX1 overexpression was rescued by EGF (EMT inducer) treatment. At last, it was uncovered that the tumor growth and metastasis were relieved after FDX1 overexpression, but these changes were reversed after EGF treatment. In conclusion, FDX1 inhibited the growth and progression of CRC by inhibiting EMT progress. This discovery hinted that FDX1 may act as an effective candidate for CRC treatment.
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Affiliation(s)
- Chao Wang
- Department of Internal Medicine Oncology, Chaohu Hospital of Anhui Medical University, No. 64, Chaohu North Road, Juchao District, Chaohu, 238000, Anhui, China.
| | - Jingjing Guo
- Department of Internal Medicine Oncology, Chaohu Hospital of Anhui Medical University, No. 64, Chaohu North Road, Juchao District, Chaohu, 238000, Anhui, China
| | - Yun Zhang
- Department of Internal Medicine Oncology, Chaohu Hospital of Anhui Medical University, No. 64, Chaohu North Road, Juchao District, Chaohu, 238000, Anhui, China
| | - Shusheng Zhou
- Department of Internal Medicine Oncology, Chaohu Hospital of Anhui Medical University, No. 64, Chaohu North Road, Juchao District, Chaohu, 238000, Anhui, China
| | - Bing Jiang
- Department of Gastrointestinal Surgery, Chaohu Hospital of Anhui Medical University, Chaohu, 238000, Anhui, China
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Louis M, Akhtar A, Ayinde B, Grabill N, Foxhall E, Murdoch E, Sarmiento Garzon D. Early Detection and Quality Indicators: Assessing the Clinical Impact and Effectiveness of Lowering the Colorectal Cancer Screening Age. Cureus 2025; 17:e78911. [PMID: 40092018 PMCID: PMC11908823 DOI: 10.7759/cureus.78911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Accepted: 02/12/2025] [Indexed: 03/19/2025] Open
Abstract
Objective With colorectal cancer (CRC) being a leading cause of cancer-related deaths globally, early detection through screening is critical for improving survival rates. Recent guidelines recommend lowering the initial screening age from 50 to 45 years based on increasing CRC incidence among younger adults. Methodology This retrospective study evaluates the impact of this adjustment on adenoma detection rates (ADR), a validated quality indicator of screening colonoscopies. We conducted a retrospective analysis of 2,792 patients who underwent colonoscopy screening at a major healthcare institution. Patients were categorized into three age groups: 45-49, 50-59, and 60-75 years. We compared ADR across these groups with a focus on evaluating the consistency of ADR in the newly included younger age group against established benchmarks. Result The ADRs for the 45-49 age group were 51.2% (105/205) in male patients and 38.5% (116/301) in female patients, closely mirroring those of the 50-59 age group at 51.08% (188/368) in male patients and 34.80% (133/382) in female patients, with no significant reduction in detection rates. Gender-specific analysis revealed higher ADR in male patients across all age groups. These findings were statistically significant when comparing procedure type with age group and gender (p < 0.05). Conclusion The study supports maintaining the already established ADR for the new age group of 45-49 as the ADR was comparable to those in the older groups. Similar polyp biopsy +/- removal rates in the 45-49-year-old age group (43.6%; 221/506) compared to the older age group (42.7%; 320/750) is also an indirect measure of the effectiveness of early screening for colon cancer.
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Affiliation(s)
- Mena Louis
- General Surgery, Northeast Georgia Medical Center Gainesville, Gainesville, USA
| | - Adeel Akhtar
- Internal Medicine, Northeast Georgia Medical Center Gainesville, Gainesville, USA
| | - Bolaji Ayinde
- Internal Medicine, Northeast Georgia Medical Center Gainesville, Gainesville, USA
| | - Nathaniel Grabill
- Surgery, Northeast Georgia Medical Center Gainesville, Gainesville, USA
| | - Edward Foxhall
- Surgery, Northeast Georgia Medical Center Gainesville, Gainesville, USA
| | - Emily Murdoch
- Trauma and Acute Care Surgery, Northeast Georgia Medical Center Gainesville, Gainesville, USA
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Yang H, Han Z, Yang Y, Zhou S, Zhang B, He J, He X, Wang N. Expression, prognosis, immunological infiltration, and DNA methylation of members of the SFRP gene family in colorectal cancer: a comparative bioinformatic and experimental analysis. In Vitro Cell Dev Biol Anim 2025; 61:149-164. [PMID: 39729237 DOI: 10.1007/s11626-024-00998-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 11/13/2024] [Indexed: 12/28/2024]
Abstract
This study aimed to investigate the expression, prognostic significance, methylation, and immune invasion levels of secreted frizzled-related proteins (SFRP1-5) in colorectal cancer (CRC). Additionally, the relationship between SFRP1/2 methylation and immune infiltration in CRC was explored. The expression of SFRP1-5 was analyzed using several databases, including GEO, TCGA, TIMER, STRING, and GEPIA. Molecular interactions with SFRPs were examined via Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, and Genomes (KEGG) pathway analyses were conducted using the DAVID database. Methylation levels of SFRP1/2 in CRC were assessed through methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) experiments. Apoptosis and proliferation in CRC cells following the knockdown of SFRP1/2 expression were evaluated using flow cytometry and CCK-8 assays. The TISIDB database was used to analyze the relationship between SFRP1/2 methylation levels and immune infiltration. The expression of SFRP1, SFRP2, and SFRP5 was significantly lower in CRC patients, while SFRP4 expression was higher compared to that in healthy individuals. Elevated mRNA expression of SFRP2 was significantly associated with improved overall survival (OS), disease-specific survival, and progression-free intervals. SFRP1/2 expression was also linked to immune invasion, with higher levels correlating with increased immune infiltration. Both SFRP1 and SFRP2 showed hypermethylation in CRC. Knockdown of SFRP1/2 expression resulted in increased proliferation of CRC cells, and their methylation levels were inversely correlated with immune cell presence. The expression, methylation, and immune cell infiltration patterns of the SFRP family in CRC differed markedly from those in healthy individuals. These findings suggest that SFRPs may serve as potential therapeutic targets and key genes associated with immune cell infiltration in CRC.
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Affiliation(s)
- Haicheng Yang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Zhuo Han
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Ying Yang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Shuai Zhou
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Bo Zhang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Jiaxing He
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Xianli He
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Nan Wang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China.
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18
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Mitev S, Saeed H, Rasheed CF, Abdullah A, Murvakov S, Sirakov V, Tchernodrinski S, Spassova Z. Texture and color enhancement imaging versus white light imaging for the detection of colorectal adenomas: Systematic review and meta-analysis. Endosc Int Open 2025; 13:a24749676. [PMID: 39958660 PMCID: PMC11827751 DOI: 10.1055/a-2474-9676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/13/2024] [Indexed: 02/18/2025] Open
Abstract
Background and study aims Texture and color enhancement imaging (TXI) is a novel optical technology designed to improve visibility during endoscopy by highlighting subtle differences in morphology and color. This systematic review and meta-analysis aimed to determine whether TXI, compared with conventional white light imaging (WLI), can improve important colonoscopy quality indicators, specifically the adenoma detection rate (ADR) and adenomas per colonoscopy (APC). Patients and methods We searched PubMed, EMBASE, and the Cochrane Central for studies comparing TXI to WLI in patients undergoing colonoscopy for any indication. Risk ratios (RRs) and mean differences (MDs) were computed using a random-effects model. Results We included 1541 patients from three studies, of which two were randomized controlled trials (RCTs). TXI was used in 775 patients (50.3%). Indications for colonoscopy varied, including positive fecal immunochemical test (FIT), surveillance, and diagnostic workup for abdominal symptoms. In the pooled data, TXI significantly increased both ADR (57,8% versus 43.6%; RR 1.32; 95% confidence interval [CI] 1.20-1.46; P < 0.001; I 2 = 0%) and APC (MD 0.50; 95% CI 0.37-0.64; P < 0.001; I 2 = 0%), compared with WLI. Furthermore, TXI was more effective at detecting nonpolypoid/flat adenomas, proximal/right-sided adenomas, and adenomas ≥ 10 mm in size. Colonoscopies with TXI had shorter withdrawal times. Conclusions Our meta-analysis demonstrates that TXI significantly improves detection of colorectal adenomas in patients undergoing colonoscopy for various indications. TXI has the potential to improve overall quality of colonoscopy and contribute to colorectal cancer prevention.
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Affiliation(s)
- Stefan Mitev
- Gastroenterology Clinic, University Hospital St Ivan Rilski, Sofia, Bulgaria
| | - Humza Saeed
- Gastroenterology, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Ch Faizan Rasheed
- Gastroenterology, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - A Abdullah
- Gastroenterology, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Stefan Murvakov
- HPB Surgery and Transplantology, Military Medical Academy, Sofia, Bulgaria, Sofia, Bulgaria
| | - Vassil Sirakov
- HPB Surgery and Transplantology, Military Medical Academy, Sofia, Bulgaria, Sofia, Bulgaria
| | - Stefan Tchernodrinski
- Division of Academic Internal Medicine and Geriatrics, University of Illinois Chicago, Chicago, United States
| | - Zoya Spassova
- Gastroenterology Clinic, University Hospital St Ivan Rilski, Sofia, Bulgaria
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19
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Feng XX, Wang JJ, Dong AQ. Expression of SPNS2 in colorectal cancer and its role in colorectal cell proliferation and migration. Shijie Huaren Xiaohua Zazhi 2024; 32:919-926. [DOI: 10.11569/wcjd.v32.i12.919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/26/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Sphingosine-1-phosphate transporter 2 (SPNS2) is involved in various tumor biological processes, but its expression status and function in colorectal cancer (CRC) have not been clarified yet.
AIM To investigate SPNS2 expression in CRC tissues and explore its role and mechanisms in proliferation, invasion, and migration of SW620 cells.
METHODS The expression profile data of CRC were retrieved from the Cancer Genome Atlas (TCGA) database. The expression difference of SPNS2 in CRC and normal tissues was analyzed using R, and verified using the Human Protein Atlas (HPA) database. The relationship between SPNS2 expression and the prognosis of patients was analyzed through the Kaplan-Meier Plotter website. After downregulating the expression of SPNS2 in SW620 cells by transfecting si-SPNS2, the proliferation, migration and invasion capabilities of the cells were assessed through the WST-8 assay, colony formation assay, scratch assay, and Transwell cell invasion assay. Concurrently, the expression levels of proteins related to cell proliferation, epithelial-mesenchymal transition (EMT), and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, AKT) signaling pathway were analyzed via Western blot.
RESULTS The TCGA expression profile data analysis showed that SPNS2 was significantly upregulated in CRC tissues, which was confirmed using the HPA database. Kaplan-Meier Plotter analysis showed that patients with high expression of SPNS2 had a poor prognosis. Compared to the control group, transfection with si-SPNS2 significantly inhibited SPNS2 expression in SW620 cells, leading to a notable reduction in their proliferation capability, colony formation rate, cell migration rate, and cell invasion rate. Additionally, Western blot analysis indicated that SPNS2 knockdown resulted in increased E-cadherin expression in SW620 cells, while simultaneously decreasing the expression levels of proliferating cell nuclear antigen, Ki-67 antigen, N-cadherin, Snail, matrix metallopeptidase 9, p-PI3K/PI3K, and p-AKT/AKT.
CONCLUSION SPNS2 is upregulated in CRC. Knockdown of SPNS2 can inhibit the proliferation, invasion, and migration of SW620 cells, and the mechanism may be related to the regulation of proliferation, EMT, and expression of PI3K/AKT signaling pathway-related proteins.
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Affiliation(s)
- Xing-Xing Feng
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang Province, China
| | - Jia-Jie Wang
- Department of Pharmacy, Taizhou Enze Hospital, Taizhou 318050, Zhejiang Province, China
| | - Ai-Qin Dong
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang Province, China
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20
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Zhang M, Liu R, Jiang W, Li H, Zhang S, Cheng W, Ye X, He J, Liu Y, Jing A, Song Y, Wang D, Liu X, Zhang B, Wang X, Ji J. A novel piperine derivative HJ-23 exhibits anti-colorectal cancer effects by activating the p53 pathway. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024:10.1007/s00210-024-03707-2. [PMID: 39718615 DOI: 10.1007/s00210-024-03707-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 12/04/2024] [Indexed: 12/25/2024]
Abstract
There has been an increase in the incidence and poor prognosis of colorectal cancer in recent years. In several studies, piperine has been shown to inhibit colon cancer cell growth and induce apoptosis. This study aimed to investigate whether a novel piperine-derived compound, HJ-23 (2,2-difluorobenzo[d][1,3]dioxol-5-yl)(4-(2,4-difluorophenyl)piperazin-1-yl)methanone), can effectively inhibit the development of colorectal cancer through specific molecular mechanisms. The MTT method was used to evaluate the effect of HJ-23 on the viability of colorectal cancer cells. The effectiveness of the compound was further confirmed by antiproliferation experiments in cell and chicken embryo models. In addition, RNA sequencing (RNA-Seq) was used to analyze changes in gene expression, and gene set enrichment analysis (GSEA) was used to identify pathways regulated by HJ-23. MTT assay, clone formation assay, and chicken embryo assay all confirmed that HJ-23 could significantly inhibit the proliferation of colorectal cancer cells. RNA-Seq analysis showed that HJ-23 significantly downregulated the expression of the tumor proliferation marker Mki67. GSEA showed that HJ-23 mainly regulated cell proliferation and cell cycle processes by activating the p53 pathway and inhibiting the E2F transcription factor (E2F) pathway. HJ-23 exhibits significant anti-tumor effects by activating the p53 pathway and inhibiting tumor cell proliferation. These findings suggest that HJ-23 is a promising drug candidate for treating colorectal cancer.
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Affiliation(s)
- Meiqi Zhang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Ruotong Liu
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Wentao Jiang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Hanxue Li
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Siyi Zhang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Wenhao Cheng
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xiaoqing Ye
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Jingliang He
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Yuanyuan Liu
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Aixin Jing
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Yizhuo Song
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Dan Wang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xing Liu
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Boyu Zhang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xiujun Wang
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
| | - Jing Ji
- Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
- College of Pharmacy and Chemistry and Chemical Engineering, Taizhou University, Taizhou, China.
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21
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Yao J, Chen G. The global, regional, and national alcohol-related colorectal cancer burden and forecasted trends: results from the global burden of disease study 2021. Front Nutr 2024; 11:1520852. [PMID: 39777070 PMCID: PMC11704491 DOI: 10.3389/fnut.2024.1520852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Background The mortality of colorectal cancer (CRC) is increasing year by year and poses a significant global health burden. Many studies have demonstrated that alcohol consumption is an important risk factor for CRC and is closely associated with malignant metastasis in CRC patients, which in turn leads to a poor prognosis. Methods This study aimed to quantify the global, regional, and national burden of alcohol-related CRC between 1990 and 2021. First, numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) for alcohol-related CRC in 2021 were analyzed at different levels. Temporal trends in the burden of disease from 1990 to 2021 were analyzed through linear regression models. Finally, both Age-Period-Cohort (APC) models and Bayesian Age-Period-Cohort (BAPC) models were utilized to project the future burden of the disease for 2022-2046. Results The global burden of disease for alcohol-related CRC is higher in 2021 compared to 1990. Male and older age groups are at high risk. Disease burden varies very much between Sociodemographic Index (SDI) regions, Global Burden of Disease (GBD) regions and countries. From 1990 to 2021, the number of cases increased, but the Age-Standardized Rate (ASR) decreased. The trends in disease burden predicted by the two models for 2022-2046 were not consistent. Conclusion This study describes the burden of disease in alcohol-related CRC and emphasizes that alcohol is a non-negligible risk factor for CRC. In order to mitigate harm, we need to strengthen disease surveillance, early prevention, timely detection, and improved treatment measures, with different approaches and responses for different regions.
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Affiliation(s)
| | - Guo Chen
- Department of Oncology, Shuguang Anhui Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (The First Affiliated Hospital West District of Anhui University of Chinese Medicine), Hefei, China
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22
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Guzowska M, Dziendzikowska K, Kopiasz Ł, Gajewska M, Wilczak J, Harasym J, Czerwińska M, Gromadzka-Ostrowska J. Oat Beta-Glucans Modulate the Gut Microbiome, Barrier Function, and Immune Responses in an In Vivo Model of Early-Stage Colorectal Cancer. Int J Mol Sci 2024; 25:13586. [PMID: 39769349 PMCID: PMC11677220 DOI: 10.3390/ijms252413586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/10/2024] [Accepted: 12/16/2024] [Indexed: 01/04/2025] Open
Abstract
Oat beta-glucans (OBGs) are known for their beneficial effects on gut health, including anti-inflammatory and prebiotic effects. The aim of this study was to evaluate the impact of two doses (1% or 3% w/w) of dietary low-molar-mass OBG supplementation on colorectal cancer (CRC) development, immune cell profiles, intestinal barrier protein expression, and microbiota composition in a rat model of CRC induced by azoxymethane (AOM). Microbiome analysis revealed significant differences between the control and CRC groups. OBG supplementation influenced microbial diversity and abundance, particularly increasing the population of beneficial bacteria, such as Lachnospiraceae and Ruminococcaceae, associated with butyrate production. However, higher doses of OBG (3%) led to a decrease in butyrate-producing bacteria and a shift toward higher levels of Akkermansia muciniphila and Enterococcus faecalis. Immune cell profiling showed a higher percentage of T lymphocytes (CD3+) in rats fed a diet supplemented with 3% OBG, both in the intraepithelial (IEL) and lamina propria lymphocytes (LPLs). Immunohistochemical analysis of the large intestine revealed a significantly elevated expression of intestinal barrier proteins, i.e., claudin 3 and 4 in rats receiving 1% OBG, while claudin 7 expression was reduced in early-stage CRC. Gene expression analysis also revealed a significant downregulation of Cldn1 in CRC rats. These findings suggest that dietary OBG supplementation modulates the gut microbiota, immune response, and intestinal barrier integrity, with potential implications for nutritional CRC development prevention and treatment strategies.
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Affiliation(s)
- Magdalena Guzowska
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Katarzyna Dziendzikowska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Łukasz Kopiasz
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Małgorzata Gajewska
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Jacek Wilczak
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Joanna Harasym
- Department of Biotechnology and Food Analysis, Wroclaw University of Economics and Business, 53-345 Wroclaw, Poland;
| | - Malwina Czerwińska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Joanna Gromadzka-Ostrowska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
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Lv K, He T. Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets. MOLECULAR BIOMEDICINE 2024; 5:70. [PMID: 39680287 PMCID: PMC11649616 DOI: 10.1186/s43556-024-00233-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 11/04/2024] [Accepted: 11/19/2024] [Indexed: 12/17/2024] Open
Abstract
Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven to be a formidable challenge, yielding limited success on a broad scale. The tumor microenvironment(TME), a critical niche for cancer cell survival, presents a novel way for cancer treatment. Cancer-associated fibroblast (CAF), as a main component of TME, is a dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span the entire spectrum of tumor development, metastasis, drug resistance, and prognosis. A thorough understanding of CAFs functions and therapeutic advances holds significant clinical implications. In this review, we underscore the heterogeneity of CAFs by elaborating on their origins, types and function. Most importantly, by elucidating the direct or indirect crosstalk between CAFs and immune cells, the extracellular matrix, and cancer cells, we emphasize the tumorigenicity of CAFs in cancer. Finally, we highlight the challenges encountered in the exploration of CAFs and list targeted therapies for CAF, which have implications for clinical treatment.
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Affiliation(s)
- Keke Lv
- Department of Hepatopanreatobiliary Surgery, Changhai Hospital, 168 Changhai Road, Yangpu District, Shanghai, 200433, China
| | - Tianlin He
- Department of Hepatopanreatobiliary Surgery, Changhai Hospital, 168 Changhai Road, Yangpu District, Shanghai, 200433, China.
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24
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Bai J, Wang Z, Yang M, Xiang J, Liu Z. Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer. Clin Exp Metastasis 2024; 41:971-988. [PMID: 39424682 DOI: 10.1007/s10585-024-10316-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 09/23/2024] [Indexed: 10/21/2024]
Abstract
Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, primarily due to liver metastasis. This study explores the role of centromere protein N (CENP-N) in mediating the methylation of septin 9 (SEPT9) and its subsequent effects on aerobic glycolysis and liver metastasis in CRC. We employed in vitro and in vivo experiments, including single-cell RNA sequencing, methylation-specific PCR (MSP), ChIP assays, and various functional assays to assess the impact of CENP-N and SEPT9 on CRC cell proliferation, migration, invasion, and metabolic reprogramming. Our data reveal that CENP-N directly interacts with SEPT9, enhancing its methylation at specific lysine residues. This modification significantly upregulates key glycolytic enzymes, thereby promoting aerobic glycolysis, CRC cell proliferation, and migration. In vivo studies further demonstrate that the CENP-N/SEPT9 axis facilitates liver metastasis of CRC, as confirmed by fluorescence imaging and histological analysis. This study identifies a novel pathway where CENP-N-mediated methylation of SEPT9 drives metabolic reprogramming and metastasis in CRC. These findings suggest potential therapeutic targets for inhibiting CRC progression and liver metastasis, offering new insights into CRC pathogenesis.
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Affiliation(s)
- Junge Bai
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 Health Road, Nangang District, Harbin, Heilongjiang, 150081, China
| | - Zhexue Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Ming Yang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Jun Xiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
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25
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Zhou X, Guo L, Yang Z, Xu H, Zhang Z, Zhang X. Impact of Chondroitin Sulfate Proteoglycan 4 Pseudogene 12 Genetic Variants on Colorectal Cancer Risk: A Case-Control Study. DNA Cell Biol 2024; 43:596-604. [PMID: 39421940 DOI: 10.1089/dna.2024.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024] Open
Abstract
This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of CSPG4P12 (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of CSPG4P12 single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The CSPG4P12 exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: p = 0.006; CA + AA vs. CC: p = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: p = 0.024; CA + AA vs. CC: p = 0.014) and younger individuals (CA vs. CC: p = 0.004; CA + AA vs. CC: p = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001) and nondrinkers (CA vs. CC: p = 0.002; CA + AA vs. CC: p = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: p = 0.016; CA + AA vs. CC: p = 0.036) and nondrinkers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Haplotype analysis showed that the CSPG4P12 Trs2880765Crs6496932Grs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (CSPG4P12 Ars2880765Crs6496932Crs8040855) (OR = 0.46, 95% CI = 0.26-0.82, p = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.
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Affiliation(s)
- Xianlei Zhou
- School of Public Health, North China University of Science and Technology, Tangshan, China
- Hebei Key Laboratory of Occupational Health and Safety for Coal Industry, Tangshan, China
| | - Liwen Guo
- College of Life Sciences, North China University of Science and Technology, Tangshan, China
| | - Zhenbang Yang
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Hongxue Xu
- School of Public Health, North China University of Science and Technology, Tangshan, China
| | - Zhi Zhang
- Affiliated Tangshan Gongren Hospital, North China University of Science and Technology, Tangshan, China
| | - Xuemei Zhang
- School of Public Health, North China University of Science and Technology, Tangshan, China
- Hebei Key Laboratory of Occupational Health and Safety for Coal Industry, Tangshan, China
- College of Life Sciences, North China University of Science and Technology, Tangshan, China
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26
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Drittone D, Schipilliti FM, Arrivi G, Mazzuca F. Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy applications in upper and lower gastrointestinal cancer, a review. Oncol Rev 2024; 18:1496141. [PMID: 39659741 PMCID: PMC11628282 DOI: 10.3389/or.2024.1496141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/14/2024] [Indexed: 12/12/2024] Open
Abstract
Peritoneal metastases (PM) are the spread of tumor forms into the peritoneum as metastases from another organ. PM is a frequent condition in metastatic gastrointestinal cancer (colorectal, gastric, pancreatic, appendiceal, and cholangiocarcinoma); their presence confers a poor prognosis, reducing patient survival. The standard treatment consists of systemic chemotherapy according to current guidelines. In recent years, scientific evidence has shown how combined cytoreductive surgery (CRS) techniques followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival in this patient population. Despite the results still obtained, using this combined technique is still under discussion. This review aims to highlight the benefits and limitations of this combined procedure, which is already widely used to treat peritoneal metastases in gynecological tumors.
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Affiliation(s)
- Denise Drittone
- Medical Oncology Unit, Sant’Andrea Hospital in Rome, Rome, Italy
| | | | - Giulia Arrivi
- Oncology Unit, Department of Clinical and Molecular Medicine, Azienda Ospedaliera Universitaria Sant’Andrea, Sapienza University of Rome, Rome, Italy
- PhD School in Translational Medicine and Oncology, Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
| | - Federica Mazzuca
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Rome, Italy
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27
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Lupan I, Silaghi C, Stroe C, Muntean A, Deleanu D, Bintintan V, Samasca G. The Importance of Genetic Screening on the Syndromes of Colorectal Cancer and Gastric Cancer: A 2024 Update. Biomedicines 2024; 12:2655. [PMID: 39767561 PMCID: PMC11674014 DOI: 10.3390/biomedicines12122655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/15/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
Gastrointestinal cancers (GIC), encompassing colonic, rectal, and gastric malignancies, rank among the most prevalent cancer types globally, contributing significantly to cancer-related mortality. In the scientific literature, various syndromes associated with colorectal and gastric cancers have been elucidated, highlighting the intricate interplay between genetic factors and disease manifestation. The primary objective of this study was to conduct a genetic exploration aimed at elucidating these associations and identifying shared genetic determinants across these cancer types. Notably, considerable research has focused on the KRAS gene mutations, polymorphisms in nucleic acids, the Wnt signaling pathway, and the role of chemokine ligands in tumorigenesis. While investigations into natural plant extracts as potential therapeutic agents are still in their nascent stages, they represent a promising avenue for future research. Ongoing studies are essential to uncover suitable biomarkers that could facilitate the identification and understanding of the genetic links between these GIC. This exploration not only seeks to enhance our comprehension of the underlying genetic architecture but also aims to inform the development of targeted therapies and preventive strategies.
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Affiliation(s)
- Iulia Lupan
- Department of Molecular Biology, Babes-Bolyai University, 400084 Cluj-Napoca, Romania;
| | - Ciprian Silaghi
- Department of Biochemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Claudia Stroe
- Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.S.); (A.M.); (D.D.)
| | - Adriana Muntean
- Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.S.); (A.M.); (D.D.)
| | - Diana Deleanu
- Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.S.); (A.M.); (D.D.)
| | - Vasile Bintintan
- Department of Surgery 1, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Gabriel Samasca
- Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (C.S.); (A.M.); (D.D.)
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28
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Shumilova VN, Goncharov AE, Azarov DV, Sitkin SI, Latariya EL, Aslanov BI, Bobrakov MA, Topuzov RE. Detection of genetic determinants of potentially oncogenic representatives of the intestinal microbiota as biomarkers of colorectal cancer. JOURNAL OF MICROBIOLOGY, EPIDEMIOLOGY AND IMMUNOBIOLOGY 2024; 101:668-678. [DOI: 10.36233/0372-9311-564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Relevance. Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. Non-invasive diagnostic methods based on the determination of hidden blood in the stool (fecal immunochemical test, guaiac test), which have been proven to be effective in clinical studies, are used for CRC screening. However, a significant disadvantage of the available non-invasive diagnostic methods is the low sensitivity in detecting the oncological process at the early stages. A number of recent studies discuss the relationship between the disease and various potentially oncogenic microorganisms in the human intestinal tract, which can be used to expand the arsenal of non-invasive methods for diagnosing CRC based on molecular genetic examination of a stool sample to identify oncogenic microorganisms.
The aim of this study was to evaluate the possibility of using genetic determinants of potentially oncogenic microorganisms as markers for colorectal cancer, based on a comparison of their prevalence in groups of patients with colorectal cancer, facultative precancerous diseases and patients without intestinal pathology.
Materials and methods. 215 participants were included in the "case–control" study: 70 patients with newly diagnosed colorectal cancer, 70 patients with inflammatory bowel disease, 75 participants without diagnosed intestinal pathology. Polymerase chain reaction (PCR) was used to identify and detect genes of potentially oncogenic microorganisms.
Results and discussion. An association was found between CRC and the presence of the Bacteroides fragilis fragilisin gene (OR 7.00; 95% CI: 2.55–22.50; p 0.001), species-specific genes of the periodontal pathogenic microorganisms Fusobacterium nucleatum (OR 5.61; 95% CI: 2.87–11.30; p 0.001) and Porphyromonas gingivalis (OR 16.3; 95% CI: 4.33–106.00; p 0.001), the clbB gene of pks pathogenicity island of the Enterobacteria (OR 3.44; 95% CI: 1.39–8.51; p = 0.010).
Conclusion. The presence of genetic markers of potentially oncogenic bacterial species and genotypes in the gut microbiome is associated with colorectal cancer. The results obtained support the possibility of using molecular genetic detection of the studied potentially oncogenic microorganisms as a method for non-invasive diagnosis of CRC.
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Shao Y, Yu M, Zhang L, Zhou L, Yan X, Feng B, Zhang S. In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies. Sci Rep 2024; 14:28535. [PMID: 39558044 PMCID: PMC11574123 DOI: 10.1038/s41598-024-79893-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 11/13/2024] [Indexed: 11/20/2024] Open
Abstract
Colorectal cancer (CRC) lymph node metastasis (LNM) is a crucial factor affecting the prognosis and treatment outcomes of CRC patients. It has been confirmed that altered glycosylation is a key event during CRC lymphatic metastases. Sialylation is one of the most significant glycosylation alterations in tumors. However, the predictive role of sialylation and sialylated protein in CRC remains elusive, especially in CRC-LNM. In this study, we explored and identified 1102 sialylated glycoproteins in CRC-LNM using metabolic labeling strategy and proteomics analysis. Combined with comprehensive analysis with bioinformatics and machine learning algorithms, we screened 25 prognostic sialylation-related genes (SRGs) to construct a new molecular phenotype (LRSRGs-Phenotype) and a prognostic SRG signature (LRSRGs-related Gene Signature) in CRC. Then, we further confirmed that patients in different phenotypes had different prognosis, molecular biological characteristics, immune cell infiltration and could be closely linked to three previously reported immune phenotypes: immune-excluded (Phenotype A), immune-desert (Phenotype B), and immune-inflamed (Phenotype C). Besides, we evaluated and validated the LRSRGs-related gene (ACADM, EHD4, FLOT1, GPC1, GSR, LRRC8A, NGFR, SDHB, and SEC61G) signature and found the risk score was an independent risk factor for CRC prognosis. CRC patients in different risk groups had different somatic mutation, tumor microenvironment and immunotherapy response. Finally, we also identified the potential therapeutic agents for CRC patients in different risk groups. In conclusion, we explored the key sialylated glycoproteins, which may play a key role in tumor LNM and clinical outcomes. And constructed the LRSRGs-phenotype and signature with prognostic and therapeutic predictive value in CRC, hoping to provide reliable scientific basis for future treatments in CRC patients.
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Affiliation(s)
- Yanfei Shao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengqin Yu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Luyang Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Leqi Zhou
- Department of colorectal surgery, Changhai Hospital, Naval Mdical University, Shanghai, China
| | - Xialin Yan
- Department of Colorectal Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Bo Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Sen Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Song D, Hou S, Ma N, Yan B, Gao J. Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of advanced colorectal cancer: a systematic review and meta-analysis. Front Immunol 2024; 15:1485303. [PMID: 39555073 PMCID: PMC11563947 DOI: 10.3389/fimmu.2024.1485303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 10/15/2024] [Indexed: 11/19/2024] Open
Abstract
Background The efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in the treatment of advanced colorectal cancer is controversial. This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors for advanced colorectal cancer. Methods PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), overall response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis. Results 12 articles with 566 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%). Conclusion PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown promising clinical responses in the treatment of colorectal cancer (CRC). Although the incidence of adverse reactions is high, they are generally tolerable. Systematic review registration https://inplasy.com/, identifier INPLASY202480030.
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Affiliation(s)
- Dandan Song
- Department of Neurology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shufu Hou
- Department of Gastrointestinal Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Ning Ma
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
| | - Bing Yan
- Department of Gastrointestinal Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jing Gao
- Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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Abstract
Sirtuin 7 (SIRT7) is a member of the sirtuin family and has emerged as a key player in numerous cellular processes. It exhibits various enzymatic activities and is predominantly localized in the nucleolus, playing a role in ribosomal RNA expression, DNA damage repair, stress response and chromatin compaction. Recent studies have revealed its involvement in diseases such as cancer, cardiovascular and bone diseases, and obesity. In cancer, SIRT7 has been found to be overexpressed in multiple types of cancer, including breast cancer, clear cell renal cell carcinoma, lung adenocarcinoma, prostate adenocarcinoma, hepatocellular carcinoma, and gastric cancer, among others. In general, cancer cells exploit SIRT7 to enhance cell growth and metabolism through ribosome biogenesis, adapt to stress conditions and exert epigenetic control over cancer-related genes. The aim of this review is to provide an in-depth understanding of the role of SIRT7 in cancer carcinogenesis, evolution and progression by elucidating the underlying molecular mechanisms. Emphasis is placed on unveiling the intricate molecular pathways through which SIRT7 exerts its effects on cancer cells. In addition, this review discusses the feasibility and challenges associated with the development of drugs that can modulate SIRT7 activity.
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Affiliation(s)
- Francisco Alejandro Lagunas-Rangel
- Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, San Pedro Zacatenco, Gustavo A. Madero, 07480, Mexico City, Mexico.
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Li X, Xu L, Ou QJ, Xu H, Chen YY, Fang YJ, Zhang CX. Serum Pyridoxal 5'-Phosphate and Pyridoxic Acid Ratio Index with Prognosis of Colorectal Cancer: A Prospective Cohort Study. Nutrients 2024; 16:3685. [PMID: 39519518 PMCID: PMC11547691 DOI: 10.3390/nu16213685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 10/24/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Studies on the association between serum vitamin B6 status and colorectal cancer prognosis are limited and have yielded inconsistent results. This study investigated the association of pyridoxal 5'-phosphate (PLP) and pyridoxic acid ratio (PAr) index with colorectal cancer survival. METHODS A total of 1286 colorectal cancer patients diagnosed since 2010 were selected from the Guangdong Colorectal Cancer Cohort study. Serum levels of PLP, pyridoxal, and 4-pyridoxic acid were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. The study followed overall mortality and colorectal cancer-specific mortality until December 2023. Multivariable Cox proportional hazards regression models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Restricted cubic spline and stratified analysis were performed. RESULTS During a median follow-up of 77.36 months, 331 deaths were recorded, with 293 specifically attributed to colorectal cancer. Higher PLP levels were associated with a longer overall survival (HRQ4 vs. Q1, 0.63; 95% CI: 0.46, 0.87; p for trend = 0.008) and colorectal cancer-specific survival (HRQ4 vs. Q1, 0.62; 95% CI: 0.44, 0.87; p for trend = 0.006). Non-linear associations were observed between serum PLP and overall and colorectal cancer-specific survival (p for non-linear < 0.05). However, PAr was not significantly associated with either overall survival (HRQ4 vs. Q1, 1.03; 95% CI: 0.75, 1.41) or colorectal cancer-specific survival (HRQ4 vs. Q1, 1.01; 95% CI: 0.72, 1.42). The association between serum PLP and both overall survival and colorectal cancer-specific survival (p for interaction < 0.05) varied by alcohol drinking status. CONCLUSIONS Higher serum PLP levels, but not PAr, may be associated with improved overall and colorectal cancer-specific survival.
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Affiliation(s)
- Xue Li
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lei Xu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Qing-Jian Ou
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Huan Xu
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
| | - Yuan-Yuan Chen
- Chronic Noncommunicable Disease Prevention and Control Department, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
| | - Yu-Jing Fang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Cai-Xia Zhang
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
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Świątkowski F, Lambrinow J, Górnicki T, Jurga M, Chabowski M. The Influence of Sociodemographic Factors and Clinical Aspects on the Quality of Life of Surgically Treated Patients with Colorectal Cancer. Cancer Manag Res 2024; 16:1293-1303. [PMID: 39355765 PMCID: PMC11444071 DOI: 10.2147/cmar.s478179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 09/13/2024] [Indexed: 10/03/2024] Open
Abstract
Introduction Due to the increasing number of cases and the levels of mortality, colorectal cancer is still a major health problem. Therefore, the growing interest in the quality of life of patients and the assessment of the quality of life of patients with colorectal cancer seems to be particularly important. The aim of the study was to investigate and determine factors that have a significant impact on the QoL of patients who were diagnosed with colorectal cancer that was surgically treated in the Surgical Department of the 4th Military Clinical Hospital in Wroclaw. Methods 102 respondents were enrolled into the study. The QLQ-C30, QLQ-CR29 as well as an original questionnaire regarding the socioeconomic factors were used for the assessment. The information was supplemented with patients' clinical data. Results According to the QLQ-C30 questionnaire the average QoL of the respondents was 55%. Factors such as male gender, younger age, higher BMI, no significant weight loss, living with family, lower level of education and being professionally active have significant positive impact on QoL. In contrary, patients with more advanced and malignant cancer with tumor located in the right half of the colon had worse QoL. The particular domains of QoL influenced by these factors were also identified. Determining these factors will allow for more effective treatment, for the shortening of the hospitalization and finally for the reduction of the costs. Conclusion The better QoL of the patients with colorectal cancer treated surgically showed younger men, living with family and with the support from close people, professionally active, with primary level of education, and without significant weight loss, ie less than 5% of body weight in the last 6 months. Moreover, patients with cancer located in the left colon, at a lower stage, with a lower grading demonstrated a better QoL.
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Affiliation(s)
- Filip Świątkowski
- Department of Surgery, 4th Military Clinical Hospital, Wroclaw, 50-981, Poland
- Division of Anaesthesiologic and Surgical Nursing, Department of Nursing and Obstetrics, Faculty of Health Science, Wroclaw Medical University, Wroclaw, 51-618, Poland
| | - Jakub Lambrinow
- Department of Angiology and Internal Medicine, Wroclaw Medical University, Wroclaw, 50-556, Poland
| | - Tomasz Górnicki
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, 50-368, Poland
| | - Marta Jurga
- Student Research Club No 180, Faculty of Medicine, Wroclaw Medical University, Wroclaw, 50-367, Poland
| | - Mariusz Chabowski
- Department of Surgery, 4th Military Clinical Hospital, Wroclaw, 50-981, Poland
- Department of Clinical Surgical Sciences, Faculty of Medicine, Wroclaw University of Science and Technology, Wroclaw, 50-556, Poland
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Moreira H, Szyjka A, Bęben D, Siwiela O, Radajewska A, Stankiewicz N, Grzesiak M, Wiatrak B, Emhemmed F, Muller CD, Barg E. Genotoxic and Anti-Migratory Effects of Camptothecin Combined with Celastrol or Resveratrol in Metastatic and Stem-like Cells of Colon Cancer. Cancers (Basel) 2024; 16:3279. [PMID: 39409900 PMCID: PMC11476312 DOI: 10.3390/cancers16193279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Colorectal cancer is one of the leading and most lethal neoplasms. Standard chemotherapy is ineffective, especially in metastatic cancer, and does not target cancer stem cells. A promising approach to improve cancer treatment is the combination therapy of standard cytostatic drugs with natural compounds. Several plant-derived compounds have been proven to possess anticancer properties, including the induction of apoptosis and inhibition of cancer invasion. This study was focused on investigating in vitro the combination of camptothecin (CPT) with celastrol (CEL) or resveratrol (RSV) as a potential strategy to target metastatic (LOVO) and stem-like (LOVO/DX) colon cancer cells. Methods: The genotoxic effects that drive cancer cells into death-inducing pathways and the ability to inhibit the migratory properties of cancer cells were evaluated. The γH2AX+ assay and Fast-Halo Assay (FHA) were used to evaluate genotoxic effects, the annexin-V apoptosis assay to rate the level of apoptosis, and the scratch test to assess antimigratory capacity. Results: The results showed that both combinations CPT-CEL and CPT-RSV improve general genotoxicity of CPT alone on metastatic cells and CSCs. However, the assessment of specific double-stranded breaks (DSBs) indicated a better efficacy of the CPT-CEL combination on LOVO cells and CPT-RSV in LOVO/DX cells. Interestingly, the combinations CPT-CEL and CPT-RSV did not improve the pro-apoptotic effect of CPT alone, with both LOVO and LOVO/DX cells suggesting activation of different cell death mechanisms. Furthermore, it was found that the combinations of CPT-CEL and CPT-RSV improve the inhibitory effect of camptothecin on cell migration. Conclusions: These findings suggest the potential utility of combining camptothecin with celastrol or resveratrol in the treatment of colon cancer, including more aggressive forms of the disease. So far, no studies evaluating the effects of combinations of these compounds have been published in the available medical databases.
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Affiliation(s)
- Helena Moreira
- Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
- The Hubert Curien pluridisciplinary Institute-IPHC, UMR 7178, University of Strasbourg, 67401 Illkirch, France
| | - Anna Szyjka
- Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | - Dorota Bęben
- Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | - Oliwia Siwiela
- Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | - Anna Radajewska
- Division of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | - Nadia Stankiewicz
- Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | | | - Benita Wiatrak
- Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
| | - Fathi Emhemmed
- The Hubert Curien pluridisciplinary Institute-IPHC, UMR 7178, University of Strasbourg, 67401 Illkirch, France
| | - Christian D. Muller
- The Hubert Curien pluridisciplinary Institute-IPHC, UMR 7178, University of Strasbourg, 67401 Illkirch, France
| | - Ewa Barg
- Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland
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Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: Recent advances in management and treatment. World J Clin Oncol 2024; 15:1136-1156. [PMID: 39351451 PMCID: PMC11438855 DOI: 10.5306/wjco.v15.i9.1136] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 06/11/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Jad El Masri
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Hiam Fakhereddine
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Joe Youssef
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Chrystelle Chemaly
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Samer Doughan
- Department of Surgery, American University of Beirut Medical Center, Beirut 1107-2020, Lebanon
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
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Zong ZP, Wu C. Clinical significance of peripheral blood UL16 and DR-70 for the early diagnosis and prognostic evaluation of colorectal cancer. World J Gastrointest Oncol 2024; 16:3832-3838. [PMID: 39350986 PMCID: PMC11438780 DOI: 10.4251/wjgo.v16.i9.3832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Early diagnosis of colorectal cancer (CRC) is of great significance to improve the survival rate and quality of life of patients, but early diagnosis of CRC requires more sensitive techniques. Peripheral blood UL16-binding protein 2 (ULBP2) and human fibrinogen degradation products (DR-70) are the main indicators for the diagnosis of malignant tumors. AIM To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference. METHODS This study involved 60 patients with early-stage CRC (CRC group), 50 patients with benign colorectal tumors (benign group), and 50 healthy patients (control group) enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January, 2020 and January, 2022. ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined. Patients with CRC were divided into the good prognosis and poor prognosis groups, and ULBP2 and DR-70 levels in the blood and diagnostic values were compared. RESULTS ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups (P < 0.05); however, no significant differences were observed between the benign and control groups (P > 0.05). Among the 60 patients with CRC followed up for two years, two died (3.33%) and 15 exhibited tumor metastasis, progression, or recurrence (25.00%). ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). A receiver operating characteristic curve was plotted. Area under the curve, sensitivity, and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices (P < 0.05) in both the good and poor prognosis groups. CONCLUSION ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC. They improved the diagnostic rate of early-stage CRC and predicted patient prognosis, thereby showing clinical application potential.
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Affiliation(s)
- Zhi-Ping Zong
- Department of Blood Transfusion, Affiliated Hospital of Jiangnan University, Wuxi 214000, Jiangsu Province, China
| | - Chen Wu
- Clinical Laboratory, Jiangsu Province Official Hospital, Nanjing 210003, Jiangsu Province, China
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Chen G, Cong LH, Gu CJ, Li P. Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging, invasion, and metastasis. World J Clin Cases 2024; 12:5492-5501. [PMID: 39188605 PMCID: PMC11269982 DOI: 10.12998/wjcc.v12.i24.5492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/06/2024] [Accepted: 06/19/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most frequently encountered malignant tumors in clinical settings. Proteins encoded by the testis-expressed gene 14 (TEX14) are imperative for spermatogenesis, necessitating intercellular bridges between germ cells. Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells. Recombinant A disintegrin and metalloprotease 17 (ADAM17) is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane. We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging, invasion, and metastasis of CRC. AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging, invasion, and metastasis. METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023. For each patient, one sample of cancer tissue and one sample of adjacent normal tissue were harvested. Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17. Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions. Clinical pathological features of neoplasm staging, invasion, and metastasis were collected, and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated. RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues. The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93% and 77.91%, respectively. There were no significant differences in age, sex, pathological type, and tumor diameter between TEX14 and ADAM17-positive and -negative patients. Patients with higher tumor differentiation degree, deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17. Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without. Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging, invasion, and metastasis. CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients, and their high expressions were associated with tumor staging, invasion, and metastasis.
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Affiliation(s)
- Gun Chen
- Department of Pathology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Ling-Hua Cong
- Department of Pathology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Chi-Jiang Gu
- Department of Gastrointestinal Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Ping Li
- Department of Pathology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
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Lin M, Liu J, Lan C, Qiu M, Huang W, Liao C, Zhang S. Factors associated with pathological complete remission after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world clinical setting. Front Oncol 2024; 14:1421620. [PMID: 39169941 PMCID: PMC11335664 DOI: 10.3389/fonc.2024.1421620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Objective This study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods We conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging. Results Postoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%). Conclusion LARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.
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Affiliation(s)
- Minglin Lin
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Junsheng Liu
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chongyuan Lan
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ming Qiu
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wei Huang
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Cun Liao
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
| | - Sen Zhang
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China
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Nie X, Zhang T, Huang X, Gu C, Zuo W, Fu LJ, Dong Y, Liu H. Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer. Cell Biol Toxicol 2024; 40:64. [PMID: 39096436 PMCID: PMC11297826 DOI: 10.1007/s10565-024-09889-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 06/03/2024] [Indexed: 08/05/2024]
Abstract
BACKGROUND AND PURPOSE Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously. EXPERIMENTAL APPROACH Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB. KEY RESULTS The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results. CONCLUSIONS AND IMPLICATIONS This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.
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Affiliation(s)
- Xusheng Nie
- Department of Gastroenterology, Yunyang County People's Hospital, Chongqing, 404599, China
| | - Tingting Zhang
- Department of Pediatrics, Rongchang District People's Hospital, Chongqing, 402460, China
| | - Xiumei Huang
- Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China
| | - Chongqi Gu
- Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China
| | - Wei Zuo
- Department of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Li-Juan Fu
- Department of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Yiping Dong
- Department of Digital Medicine, Department of Bioengineering and Imaging, Army Medical University, Chongqing, 400038, China
| | - Hao Liu
- Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China.
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Tamraz M, Al Ghossaini N, Temraz S. Optimization of colorectal cancer screening strategies: New insights. World J Gastroenterol 2024; 30:3361-3366. [PMID: 39091719 PMCID: PMC11290395 DOI: 10.3748/wjg.v30.i28.3361] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 06/07/2024] [Accepted: 06/28/2024] [Indexed: 07/24/2024] Open
Abstract
In this editorial, we discuss the article by Agatsuma et al. We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer (CRC) and its substantial impact on both incidence and mortality rates. Screening is highly recommended, and an early diagnosis stands out as the most crucial predictor of survival for CRC patients. Therefore, it is essential to identify and address the barriers hindering adherence to screening measures, as these barriers can vary among different populations. Furthermore, we focus on screening strategy optimization by selecting high-risk groups. Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage, showing no significant difference compared to patients undergoing regular screening. This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.
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Affiliation(s)
- Magie Tamraz
- Department of Nutrition and Public Health, Holy Spirit University of Kaslik, Jounieh 446, Lebanon
| | - Najib Al Ghossaini
- Department of Internal Medicine, Ain Wazein Medical Village, Chouf 1503, Lebanon
| | - Sally Temraz
- Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
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Yang SM, Liu JM, Wen RP, Qian YD, He JB, Sun JS. Correlation between abdominal computed tomography signs and postoperative prognosis for patients with colorectal cancer. World J Gastrointest Surg 2024; 16:2145-2156. [PMID: 39087101 PMCID: PMC11287691 DOI: 10.4240/wjgs.v16.i7.2145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/08/2024] [Accepted: 05/27/2024] [Indexed: 07/22/2024] Open
Abstract
BACKGROUND Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. AIM To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. METHODS The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. RESULTS For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). CONCLUSION The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.
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Affiliation(s)
- Shao-Min Yang
- Department of Radiology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan 528315, Guangdong Province, China
| | - Jie-Mei Liu
- Department of Rehabilitation Medicine, Shunde Hospital, Southern Medical University, Foshan 528399, Guangdong Province, China
| | - Rui-Ping Wen
- Department of Radiology, Lecong Hospital of Shunde, Foshan 528315, Guangdong Province, China
| | - Yu-Dong Qian
- Department of Radiology, Lecong Hospital of Shunde, Foshan 528315, Guangdong Province, China
| | - Jing-Bo He
- Department of Ultrasound, Lecong Hospital of Shunde, Foshan 528315, Guangdong Province, China
| | - Jing-Song Sun
- Department of Radiology, Lecong Hospital of Shunde, Foshan 528315, Guangdong Province, China
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Luo H, Luo W, Ding N, Zhu H, Lai J, Tang Q, He Y. Glycerophosphoinositol modulates FGA and NOTCH3 in exercise-induced muscle adaptation and colon cancer progression. Front Pharmacol 2024; 15:1430400. [PMID: 39130639 PMCID: PMC11310102 DOI: 10.3389/fphar.2024.1430400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 06/24/2024] [Indexed: 08/13/2024] Open
Abstract
Objectives Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins. Methods Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types. Results The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3. Conclusion FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.
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Affiliation(s)
- Hongbiao Luo
- Department of Anorectal Surgery, Chenzhou NO. 1 People’s Hospital, Chenzhou, Hunan, China
- Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Wei Luo
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ning Ding
- Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Huimin Zhu
- Department of Critical Care Medicine, Chenzhou NO. 1 People’s Hospital, Chenzhou, Hunan, China
| | - Jiahui Lai
- The Third Hospital, Hebei Medical University, Shijiazhuang, China
| | - Qingzhu Tang
- Department of Anorectal Surgery, Chenzhou NO. 1 People’s Hospital, Chenzhou, Hunan, China
| | - Yongheng He
- Hunan University of Chinese Medicine, Changsha, Hunan, China
- Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, China
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Wang W, Zhao X, Zhou J, Li H. A novel antitumor mechanism of triptonide in colorectal cancer: inducing ferroptosis via the SLC7A11/GPX4 axis. Funct Integr Genomics 2024; 24:126. [PMID: 39012393 DOI: 10.1007/s10142-024-01402-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/25/2024] [Accepted: 07/02/2024] [Indexed: 07/17/2024]
Abstract
Colorectal cancer (CRC) is a prevalent malignancy affecting the human digestive tract. Triptonide has been shown to have some anticancer activity, but its effect in CRC is vague. Herein, we examined the effect of triptonide on CRC. In this study, the results of bioinformatics analysis displayed that triptonide may regulate ferroptosis in CRC by modulating GPX4 and SLC7A11. In HCT116 and LoVo cells, the expression levels of GPX4 and SLC7A11 were significantly reduced after triptonide management versus the control group. Triptonide inhibited proliferation, but promoted ferroptosis in CRC cells. SLC7A11 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide inhibited activation of the PI3K/AKT/Nrf2 signaling in CRC cells. Activation of the PI3K/AKT signaling or Nrf2 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide suppressed CRC cell growth in vivo by modulating SLC7A11 and GPX4. In conclusion, Triptonide repressed proliferation and facilitated ferroptosis of CRC cells by repressing the SLC7A11/GPX4 axis through inactivation of the PI3K/AKT/Nrf2 signaling.
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Affiliation(s)
- Weijie Wang
- Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, No. 804 Shengli South Street, Xingqing District, Yinchuan City, 750004, China
| | - Xiaofen Zhao
- Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, No. 804 Shengli South Street, Xingqing District, Yinchuan City, 750004, China
| | - Jie Zhou
- Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, No. 804 Shengli South Street, Xingqing District, Yinchuan City, 750004, China
| | - Hai Li
- Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, No. 804 Shengli South Street, Xingqing District, Yinchuan City, 750004, China.
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Fu X, Xiong Y, Tang R, Li X, Liu H, Ren X. Association of hTERT Gene Polymorphism and Colorectal Cancer (CRC) Risk in the Chinese Han Population. TOHOKU J EXP MED 2024; 263:89-95. [PMID: 38296486 DOI: 10.1620/tjem.2024.j008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
The catalytic subunit telomerase reverse transcriptase (hTERT) is a prerequisite for malignant transformation of human cells. Colorectal cancer (CRC) is a common malignant tumor. The genetic association of hTERT gene rs2853669 and rs2736098 polymorphisms with CRC was surveyed in the Chinese population. Two hundreds patients with CRC and 200 healthy controls were taken for blood sample collection. Sanger sequencing was applied for genotyping. Multiple logistic regression analysis was performed, and odds ratio (OR) together with confidence interval (CI) were calculated to obtain the corresponding association power. Among CRC cases (49.50%), hTERT gene rs2736098 GA genotype carriers were more prevalent compared with the control group (41.00%, P = 0.035), which increased the risk of CRC by 1.576 times (95% CI, 1.031-2.409). Distribution of the rs2736098 genotypes was significantly associated with TNM stage, tumor differentiation, tumor size and lymph node metastasis (P < 0.05). The frequencies of hTERT gene rs2853669 polymorphism were not significantly different between CRC patients and healthy controls. Logistic regression analysis indicated that both body mass index (BMI) and hTERT gene rs2736098 polymorphism remained significantly correlated with CRC susceptibility. The frequencies of hTERT gene rs2853669 polymorphism did not differ significantly between CRC patients and control group (P > 0.05). The hTERT gene rs2736098 polymorphism was correlated with CRC risk in the Chinese Han population, and the GA genotype was a risk element for the onset of CRC.
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Affiliation(s)
- Xianxian Fu
- Department of Laboratory, Haikou People's Hospital
| | - Yanyan Xiong
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University
| | - Renjin Tang
- Department of Integrated Traditional Chinese and Western Medicine, Chengdu Shangjin Nanfu Hospital
| | - Xuelin Li
- Department of Integrated Traditional Chinese and Western Medicine, Chengdu Shangjin Nanfu Hospital
| | - Hong Liu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University
| | - Xiaowei Ren
- Department of Anorectal, Fuling Hospital of Chinese Medicine
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Wu HB, Liu DF, Liu YL, Wang XF, Cao YP. Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma. World J Gastrointest Surg 2024; 16:1734-1741. [PMID: 38983325 PMCID: PMC11230031 DOI: 10.4240/wjgs.v16.i6.1734] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/08/2024] [Accepted: 05/11/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.
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Affiliation(s)
- Hong-Biao Wu
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Dong-Fang Liu
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Ye-Lei Liu
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Xiao-Feng Wang
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
| | - Yue-Peng Cao
- Department of Colorectal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
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Ze Y, Tu HM, Zhao YY, Zhang L. Developing a Nomogram for Predicting Colorectal Cancer and Its Precancerous Lesions Based on Data from Three Non-Invasive Screening Tools, APCS, FIT, and sDNA. J Multidiscip Healthc 2024; 17:2891-2901. [PMID: 38903878 PMCID: PMC11189322 DOI: 10.2147/jmdh.s465286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/29/2024] [Indexed: 06/22/2024] Open
Abstract
Purpose This study aimed to develop and validate a nomogram for predicting positive colonoscopy results using the data from non-invasive screening strategies. Methods The volunteers participated in primary colorectal cancer (CRC) screenings using Asia-Pacific colorectal screening (APCS) scoring, faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing and underwent a colonoscopy. The positive colonoscopy results included CRC, advanced adenoma (AA), high-grade intraepithelial neoplasia (HGIN), and low-grade intraepithelial neoplasia (LGIN). The enrolled participants were randomly selected for training and validation sets in a 7:3 ratio. A model for predicting positive colonoscopy results was virtualized by the nomogram using logistic regression analysis. Results Among the 179 enrolled participants, 125 were assigned to training set, while 54 were assigned to validation set. After multivariable logistic regression was done, APCS score, FIT result, and sDNA result were all identified as the predictors for positive colonoscopy results. A model that incorporated the above independent predictors was developed and presented as a nomogram. The C-index of the nomogram in the validation set was 0.768 (95% CI, 0.644-0.891). The calibration curve demonstrated a good agreement between prediction and observation. The decision curve analysis (DCA) curve showed that the model achieved a net benefit across all threshold probabilities. The AUC of the prediction model for predicting positive colonoscopy results was much higher than that of the FIT + sDNA test scheme. Conclusion The nomogram for predicting positive colonoscopy results was successfully developed based on 3 non-invasive screening tools (APCS scoring, FIT and sDNA test).
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Affiliation(s)
- Yuan Ze
- Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China
| | - Hui-Ming Tu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China
| | - Yuan-Yuan Zhao
- Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China
| | - Lin Zhang
- Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230026, People’s Republic of China
- School of Population Medicine and Public Health, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, 100053, People’s Republic of China
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Fryer E, Martin RM, Haycock P, Yarmolinsky J. Investigating the causal effect of previously reported therapeutic agents for colorectal cancer prevention: protocol for a Mendelian randomization analysis. Wellcome Open Res 2024; 9:30. [PMID: 38911899 PMCID: PMC11190651 DOI: 10.12688/wellcomeopenres.20861.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 06/25/2024] Open
Abstract
Background Colorectal cancer (CRC) is the third most common cancer worldwide, with 1.9 million new cases in 2020 and a predicted rise to 3.2 million in 2040. Screening programmes are already in place to aid early detection and secondary prevention of CRC, but the rising prevalence means additional approaches are required in both primary and secondary prevention settings. Preventive therapy, whereby natural or synthetic agents are used to prevent, reverse or delay disease development, could be an effective strategy to further reduce cancer risk and potential agents have already been identified in conventional observational studies. However, as such studies are vulnerable to confounding and reverse causation, we aim to evaluate these observed relationships using Mendelian randomization (MR), an alternative causal inference approach which should be less susceptible to these biases. Methods and analysis We will use two-sample MR, which uses two independent samples for the exposure and outcome data, to investigate previously reported observational associations of multiple potential preventive agents with CRC risk. We define preventive agents as any synthetic (e.g. approved medication) or natural (e.g. micronutrient, endogenous hormone) molecule used to reduce the risk of cancer. We will first extract potential preventive agents that have been previously linked to CRC risk in observational studies from reviews of the literature. We will then evaluate whether we can develop a genetic instrument for each preventive agent from previously published genome-wide association studies (GWASs) of direct measures of molecular traits (e.g. circulating levels of protein drug targets, blood-based biomarkers of dietary vitamins). The summary statistics from these GWASs, and a large GWAS of CRC, will be used in two-sample MR analyses to investigate the causal effect of putative preventive therapy agents on CRC risk. Sensitivity analyses will be conducted to evaluate the robustness of findings to potential violations of MR assumptions.
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Affiliation(s)
- Ella Fryer
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England, BS8 2BN, UK
- Population Health Sciences, University of Bristol, Bristol, England, BS8 2BN, UK
| | - Richard M. Martin
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England, BS8 2BN, UK
- Population Health Sciences, University of Bristol, Bristol, England, BS8 2BN, UK
- NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust, University of Bristol, Bristol, England, BS8 2BN, UK
| | - Philip Haycock
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England, BS8 2BN, UK
- Population Health Sciences, University of Bristol, Bristol, England, BS8 2BN, UK
| | - James Yarmolinsky
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, England, W2 1PG, UK
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Lingam G, Shakir T, Kader R, Chand M. Role of artificial intelligence in colorectal cancer. Artif Intell Gastrointest Endosc 2024; 5:90723. [DOI: 10.37126/aige.v5.i2.90723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 04/10/2024] [Accepted: 04/19/2024] [Indexed: 05/11/2024] Open
Abstract
The sphere of artificial intelligence (AI) is ever expanding. Applications for clinical practice have been emerging over recent years. Although its uptake has been most prominent in endoscopy, this represents only one aspect of holistic patient care. There are a multitude of other potential avenues in which gastrointestinal care may be involved. We aim to review the role of AI in colorectal cancer as a whole. We performed broad scoping and focused searches of the applications of AI in the field of colorectal cancer. All trials including qualitative research were included from the year 2000 onwards. Studies were grouped into pre-operative, intra-operative and post-operative aspects. Pre-operatively, the major use is with endoscopic recognition. Colonoscopy has embraced the use for human derived classifications such as Narrow-band Imaging International Colorectal Endoscopic, Japan Narrow-band Imaging Expert Team, Paris and Kudo. However, novel detection and diagnostic methods have arisen from advances in AI classification. Intra-operatively, adjuncts such as image enhanced identification of structures and assessment of perfusion have led to improvements in clinical outcomes. Post-operatively, monitoring and surveillance have taken strides with potential socioeconomic and environmental savings. The uses of AI within the umbrella of colorectal surgery are multiple. We have identified existing technologies which are already augmenting cancer care. The future applications are exciting and could at least match, if not surpass human standards.
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Affiliation(s)
- Gita Lingam
- Department of General Surgery, Princess Alexandra Hospital, Harlow CM20 1QX, United Kingdom
| | - Taner Shakir
- Department of Colorectal Surgery, University College London, London W1W 7TY, United Kingdom
| | - Rawen Kader
- Department of Gastroenterology, University College London, University College London Hospitals Nhs Foundation Trust, London W1B, United Kingdom
| | - Manish Chand
- Gastroenterological Intervention Centre, University College London, London W1W 7TS, United Kingdom
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Su MC, Hsu CH, Chen KC, Lin JR, Li HY, Fang YT, Huang RYJ, Jeng YM. Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling. Pathobiology 2024; 91:393-410. [PMID: 38830348 PMCID: PMC11614314 DOI: 10.1159/000539612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 05/30/2024] [Indexed: 06/05/2024] Open
Abstract
INTRODUCTION The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. METHODS We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. RESULTS Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. CONCLUSION These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.
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Affiliation(s)
- Min-Cheng Su
- Department of Pathology, Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Ching-Hsiang Hsu
- Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan
| | - Ko-Chen Chen
- School of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jun-Ru Lin
- Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan
| | - Huei-Ying Li
- Medical Microbiota Center of the First Core Laboratory, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Fang
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ruby Yun-Ju Huang
- School of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yung-Ming Jeng
- Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
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Lv X, Ma W, Miao X, Hu S, Xie H. Navigating colorectal cancer prognosis: A Treg-related signature discovered through single-cell and bulk transcriptomic approaches. ENVIRONMENTAL TOXICOLOGY 2024; 39:3512-3522. [PMID: 38459654 DOI: 10.1002/tox.24214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND The significance of regulatory T cells (Tregs) in colorectal cancer is unclear. METHODS The single-cell sequencing data for colorectal cancer, specifically GSE132465 and GSE188711, were retrieved from the GEO database. Simultaneously, bulk transcriptome data were obtained from the UCSC Xena website. To delve into the heterogeneity of Treg cells and identify key genes at the single-cell sequencing level, we employed dimensionality reduction techniques alongside clustering and conducted differential expression gene analysis. For the bulk transcriptome data, we utilized weighted co-expression network analysis to investigate critical gene modules. Additionally, we employed COX regression and Lasso regression methodologies to construct prognostic models, thereby assessing patient outcomes. To facilitate outcome evaluation, nomograms were constructed. The integration of these diverse approaches aims to comprehensively study colorectal cancer, encompassing single-cell heterogeneity, key gene identification, and prognosis modeling using both single-cell and bulk transcriptome data. Polymerase chain reaction (PCR) experiments are used to verify mRNA expression levels of key genes. The analysis software was R software (version 4.3.2). RESULTS Through single-cell sequencing analysis and bulk transcriptome analysis, we constructed a prognostic model composed with Treg-associated signatures. The high-risk group demonstrated significantly worse prognosis compared with the low-risk group, highlighting the clinical relevance of our models. PCR confirmed that the key gene DEAH-box helicase 15 (DHX15) was significantly overexpressed in colorectal cancer. CONCLUSIONS The prognostic models developed in this study offer a potential tool for risk assessment, guiding treatment decisions for colorectal cancer patients.
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Affiliation(s)
- Xuening Lv
- Department of Gastroenterology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China
| | - Wen Ma
- Oncology Department II, Huai'an 82 hospital, Huai'an, Jiangsu, China
| | - Xiaye Miao
- Department of Laboratory Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China
| | - Shaohui Hu
- Department of Thoracic Surgery, Fuyang Tumour Hospital, Fuyang, China
| | - Huaibing Xie
- Department of Traditional Chinese Medicine &Oncology, Huai'an Second People's Hospital, Affiliated to Xuzhou Medical University, Huai'an, China
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