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Deng RZ, Zheng X, Lu ZL, Yuan M, Meng QC, Wu T, Tian Y. Effect of colorectal cancer stem cells on the development and metastasis of colorectal cancer. World J Gastrointest Oncol 2024; 16:4354-4368. [PMID: 39554751 PMCID: PMC11551631 DOI: 10.4251/wjgo.v16.i11.4354] [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: 07/23/2024] [Revised: 08/24/2024] [Accepted: 09/09/2024] [Indexed: 10/25/2024] Open
Abstract
The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role - immune checkpoints - and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.
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Affiliation(s)
- Run-Zhi Deng
- College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, Fujian Province, China
| | - Xin Zheng
- College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, Fujian Province, China
| | - Zhong-Lei Lu
- College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, Fujian Province, China
| | - Ming Yuan
- Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Qi-Chang Meng
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Tao Wu
- Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610044, Sichuan Province, China
| | - Yu Tian
- Department of Thoracic Surgery, Yancheng No. 1 People’s Hospital, Affiliated Hospital of Nanjing University Medical School, The First People’s Hospital of Yancheng, Yancheng 224000, Jiangsu Province, China
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Li X, Sharen G, Zhang M, Zhang L, Liu K, Wang Y, Cheng H, Hou M. High expression of PDCD11 in colorectal cancer and its correlation with the prognosis and immune cell infiltration. Heliyon 2024; 10:e35002. [PMID: 39170455 PMCID: PMC11336332 DOI: 10.1016/j.heliyon.2024.e35002] [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: 01/09/2024] [Revised: 07/20/2024] [Accepted: 07/21/2024] [Indexed: 08/23/2024] Open
Abstract
Objective To undertake a comprehensive assay of PDCD11 expression in colorectal cancer (CRC) and its association with prognosis and immune cell infiltration (ICIN) utilizing bioinformatics tools. Methods The PDCD11 expression in CRC and pan-cancer was quantified through datasets from TCGA and GEO databases, and the assay was conducted through R software and the GEPIA database. Moreover, mRNA and protein expression data of PDCD11 were attained from the HPA database. It was attempted to establish protein-protein interaction networks of PDCD11 via the STRING and GeneMANIA databases. The association of PDCD11 expression with CRC staging was evaluated through R software, while its association with CRC and pan-cancer prognosis was figured out via the GEPIA database. Furthermore, the relationship of PDCD11 expression with ICIN was assayed using R software and the TIMER database. Additionally, the influences of PDCD11 knockdown on the proliferation, apoptosis, and migration of colon cancer RKO cell lines was evaluated. Results PDCD11 exhibited elevated expression in CRC and various other malignancies, potentially indicating a promotive role in cancer progression. Overexpression of PDCD11 was found to correlate with attenuated overall survival in CRC and other malignancies. Moreover, PDCD11 demonstrated promising predictive capabilities for distinguishing between tumor and non-tumor tissues. The positive association of high PDCD11 expression with the infiltration of neutrophils, dendritic cells, CD8+ T cells, CD4+ T cells, and macrophages, as well as with the expression of immune checkpoint molecules CTLA4 and PD-1 was noteworthy. Lentivirus-mediated PDCD11 knockdown suppressed RKO cell proliferation, colony formation, and migration, while triggered apoptosis in these cells. Conclusion The outcomes unveiled the noticeable function of PDCD11 in CRC and various other malignancies, emphasizing its potential as a prognostic biomarker and therapeutic target.
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Affiliation(s)
- Xiongfeng Li
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Gaowa Sharen
- Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University & Department of Pathological Anatomy, College of Basic Medicine of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Minjie Zhang
- Department of Ultrasound, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Lei Zhang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Kejian Liu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Yu Wang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Haidong Cheng
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
| | - Mingxing Hou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia, China
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Abedizadeh R, Majidi F, Khorasani HR, Abedi H, Sabour D. Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments. Cancer Metastasis Rev 2024; 43:729-753. [PMID: 38112903 DOI: 10.1007/s10555-023-10158-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 11/27/2023] [Indexed: 12/21/2023]
Abstract
Colorectal cancer is the third most common and the second deadliest cancer worldwide. To date, colorectal cancer becomes one of the most important challenges of the health system in many countries. Since the clinical symptoms of this cancer appear in the final stages of the disease and there is a significant golden time between the formation of polyps and the onset of cancer, early diagnosis can play a significant role in reducing mortality. Today, in addition to colonoscopy, minimally invasive methods such as liquid biopsy have received much attention. The treatment of this complex disease has been mostly based on traditional treatments including surgery, radiotherapy, and chemotherapy; the high mortality rate indicates a lack of success for current treatment methods. Moreover, disease recurrence is another problem of traditional treatments. Recently, new approaches such as targeted therapy, immunotherapy, and nanomedicine have opened new doors for cancer treatment, some of which have already entered the market, and many methods have shown promising results in clinical trials. The success of immunotherapy in the treatment of refractory disease, the introduction of these methods into neoadjuvant therapy, and the successful results in tumor shrinkage without surgery have made immunotherapy a tough competitor for conventional treatments. It seems that the combination of those methods with such targeted therapies will go through promising changes in the future of colorectal cancer treatment.
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Affiliation(s)
- Roya Abedizadeh
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Fateme Majidi
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hamid Reza Khorasani
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hassan Abedi
- Department of Internal Medicine, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
| | - Davood Sabour
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran.
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran.
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Huang J, Zhao P, Shi J, Ning J, Wang Z, Luo Y, Qin J, Huang X. Prognostic Value and Immunological Role of P4HA3 in Colon Adenocarcinoma. Int J Gen Med 2023; 16:1953-1971. [PMID: 37251280 PMCID: PMC10224728 DOI: 10.2147/ijgm.s407068] [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: 02/03/2023] [Accepted: 05/05/2023] [Indexed: 05/31/2023] Open
Abstract
Purpose Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been proven to participate in the occurrence and development of multiple cancers. However, the functional role of P4HA3 in the tumor immune microenvironment (TIME) of colon adenocarcinoma (COAD) and the prognosis of COAD patients has not been clarified. This study aimed to elucidate the immunological role and prognostic value of P4HA3 in COAD. Methods P4HA3 expression in COAD tissues was analyzed via experiments and a bioinformatics algorithm. Based on the COAD patients in The Cancer Genome Atlas database, we comprehensively evaluated whether the expression levels of P4HA3 affected clinical prognosis, TIME, and immunotherapy of COAD using the R platforms and several public databases, including GEPIA, TIMER, TISIDB, and TCIA. Results The results of the pan-cancer analysis indicated that P4HA3 expression was significantly different in most tumor tissues compared with normal tissues. P4HA3 was overexpressed in COAD tissues, and overexpression of P4HA3 was associated with a worse overall survival and a shorted progression-free interval in COAD patients. The expression of P4HA3 was positively correlated with pathological stage, T stage, N stage, perineural infiltration, and lymphatic infiltration. There were significant correlations of P4HA3 expression levels with immune cell infiltration and their makers, as well as immunomodulators, chemokines, and microsatellite status. Moreover, overexpression of P4HA3 was associated with a lower response rate to immunotherapy in the IMvigor210 cohort. Conclusion Overexpression of P4HA3 is closely related to the poor prognosis of COAD patients, and P4HA3 is a potential target for immunotherapy in COAD patients.
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Affiliation(s)
- Jun Huang
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Peizhuang Zhao
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Jialing Shi
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Jiajia Ning
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Zhen Wang
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Yihua Luo
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Jingqian Qin
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Xue Huang
- Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
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Ruan GT, Song MM, Zhang KP, Xie HL, Zhang Q, Zhang X, Tang M, Zhang XW, Ge YZ, Yang M, Zhu LC, Shi HP. A novel nutrition-related nomogram for the survival prediction of colorectal cancer-results from a multicenter study. Nutr Metab (Lond) 2023; 20:2. [PMID: 36600242 DOI: 10.1186/s12986-022-00719-8] [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: 03/27/2022] [Accepted: 12/18/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Precisely predicting the short- and long-term survival of patients with cancer is important. The tumor-node-metastasis (TNM) stage can accurately predict the long-term, but not short-term, survival of cancer. Nutritional status can affect the individual status and short-term outcomes of patients with cancer. Our hypothesis was that incorporating TNM stage and nutrition-related factors into one nomogram improves the survival prediction for patients with colorectal cancer (CRC). METHOD This multicenter prospective primary cohort included 1373 patients with CRC, and the internal validation cohort enrolled 409 patients with CRC. Least absolute shrinkage and selection operator regression analyses were used to select prognostic indicators and develop a nomogram. The concordance (C)-index, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the prognostic discriminative ability of the nomogram, TNM stage, Patient-Generated Subjective Global Assessment (PGSGA), and TNM stage + PGSGA models. The overall survival (OS) curve of risk group stratification was calculated based on the nomogram risk score. RESULTS TNM stage, radical resection, reduced food intake, activities and function declined, and albumin were selected to develop the nomogram. The C-index and calibration plots of the nomogram showed good discrimination and consistency for CRC. Additionally, the ROC curves and DCA of the nomogram showed better survival prediction abilities in CRC than the other models. The stratification curves of the different risk groups of the different TNM categories were significantly different. CONCLUSION The novel nomogram showed good short- and long-term outcomes of OS in patients with CRC. This model provides a personalized and convenient prognostic prediction tool for clinical applications.
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Affiliation(s)
- Guo-Tian Ruan
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Meng-Meng Song
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Kang-Ping Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Hai-Lun Xie
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Qi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Xi Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Meng Tang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Xiao-Wei Zhang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Yi-Zhong Ge
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Ming Yang
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China.,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China
| | - Li-Chen Zhu
- Department of Immunology, School of Preclinical Medicine, Guangxi Medical University, Nanning, China
| | - Han-Ping Shi
- Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, China. .,Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, China.
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Liu Y, Guo F, Guo W, Wang Y, Song W, Fu T. Ferroptosis-related genes are potential prognostic molecular markers for patients with colorectal cancer. Clin Exp Med 2021; 21:467-477. [PMID: 33674956 DOI: 10.1007/s10238-021-00697-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 02/12/2021] [Indexed: 12/11/2022]
Abstract
Ferroptosis is a newly discovered programmed cell death that plays a vital role in the occurrence and development of tumors. However, little is known about its prognostic value of ferroptosis-related genes (FRGs) in colorectal cancer (CRC). This study was to investigate the clinical significance of FRGs on overall survival (OS) of patients with CRC. The mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to identify hub FRGs and establish a novel ferroptosis-related gene signature in predicting OS in training cohort, and assessed in the validation cohort. Then, the genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features were established. Thirteen FRGs were identified to be most significantly related to the OS of CRC patients. Based on the LASSO Cox regression algorithm, we selected 10 genes from 13 FRGs to establish a prognostic risk signature. The log-rank test and Kaplan-Meier analysis confirmed the predictive value of the risk scores for OS in CRC patients. The time-dependent receiver operating characteristic (tdROC) of signature indicates the showed powerful prediction ability in both training cohort and validation cohort. Then, a genomic-clinicopathologic nomogram integrating age, stage, and risk scores was established and demonstrated high predictive accuracy and clinical value, which was validated through tdROC and calibration curves. The ferroptosis-related gene signature and genomic-clinicopathologic nomogram could be used to predict the prognosis of CRC patients and might also be potential therapeutic targets.
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Affiliation(s)
- Yanliang Liu
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Fengqin Guo
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Wenyi Guo
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Yatao Wang
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Wei Song
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China
| | - Tao Fu
- Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China.
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