Prostaglandin F2α synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F2α-dependent and F2α-independent mechanism

Wang, Yi-Jun; Xie, Xiao-Li; Liu, Hong-Qun; Tian, Hui; Jiang, Xiao-Yu; Zhang, Jiu-Na; Chen, Sheng-Xiong; Liu, Ting; Wang, Shu-Ling; Zhou, Xue; Jin, Xiao-Xu; Liu, Shi-Mao; Jiang, Hui-Qing

doi:10.3748/wjg.v29.i39.5452

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…However, the lingering question is how the initial treatment might in uence subsequent prognosis for patients who experience recurrence. It was pertinent to examine whether the initial standard treatment including chemotherapy or radiotherapy, could induce heightened drug resistance [17][18][19][20][21] and result in a more invasive tumor pro le [22]. Our ndings revealed that patients with high-risk tumors who initially received primary surgery were administered less chemotherapy before recurrence.…”

Section: Discussionmentioning

confidence: 99%

Does the Initial Treatment of the Primary Tumor Impact Prognosis after Recurrence in Locally Advanced Rectal Cancer? Results From A Retrospective Cohort Analysis

Wang,

Bai,

Chen

et al. 2024

Preprint

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Introduction: Role of neoadjuvant therapy (NAT) for local advanced rectal cancer (LARC) has been well proved, but its impact on patients who relapse remains unknown. This study aims to delineate the influence of initial treatment and MRI-defined risk factors on post recurrent survival in recurrent LARC patients. Patients and methods: LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified based on MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). They were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. Result 381 cases of relapsed patients were identified from 2,329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients with single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival time after recurrence (P < 0.001). Patients in the HiS group showed poorer survival after recurrence compared to the other three subgroups (P = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval compared to the other groups (P = 0.001). Conclusions Our findings reaffirm the prognostic significance of salvage surgery in relapsed patients from a LARC cohort. Moreover, MRI defined high-risk LARC patients who received upfront surgery without NAT had shorter interval to recurrence and poorer survival outcome after recurrence. Our result underscore the critical role of NAT in improving patients’ survival after recurrence. Trial registration: Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Does the Initial Treatment of the Primary Tumor Impact Prognosis after Recurrence in Locally Advanced Rectal Cancer? Results From A Retrospective Cohort Analysis

Wang,

Bai,

Chen

et al. 2024

Preprint

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Does the initial treatment of primary tumor impact prognosis after recurrence in locally advanced rectal cancer? Results from a retrospective cohort analysis

Wang,

Bai,

Chen

et al. 2024

Int J Colorectal Dis

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Introduction The role of neoadjuvant therapy (NAT) in the treatment of locally advanced rectal cancer (LARC) has been well proven, but its impact on patients who relapse remains unknown. This study aims to elucidate the influence of initial treatment and MRI-defined risk factors on postrecurrent survival in patients with LARC recurrence. Patients and methods LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified on the basis of MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). The patients were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. Results A total of 381 patients who experienced relapse were identified from among 2329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients who experienced single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival times after recurrence ( P < 0.001). Patients in the HiS group had poorer survival after recurrence than those in the other three groups ( P = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval than those in the other groups ( P = 0.001). Conclusions Our findings reaffirm the prognostic significance of salvage surgery in patients from a LARC cohort who experienced relapse. Moreover, MRI-defined high-risk LARC patients who received upfront surgery without NAT had shorter intervals of recurrence and poorer survival outcomes after recurrence. Our results highlight the critical role of NAT in improving patient survival after recurrence. Trial registration Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1007/s00384-024-04721-9.

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CTR-DB 2.0: an updated cancer clinical transcriptome resource, expanding primary drug resistance and newly adding acquired resistance datasets and enhancing the discovery and validation of predictive biomarkers

Jiang,

Ma,

Yang

et al. 2024

Nucleic Acids Research

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Drug resistance is a principal limiting factor in cancer treatment. CTR-DB, the Cancer Treatment Response gene signature DataBase, is the first data resource for clinical transcriptomes with cancer treatment response, and meanwhile supports various data analysis functions, providing insights into the molecular determinants of drug resistance. Here we proposed an upgraded version, CTR-DB 2.0 (http://ctrdb.ncpsb.org.cn). Around 190 up-to-date source datasets with primary resistance information (129% increase compared to version 1.0) and 13 acquired-resistant datasets (a new dataset type), covering 10 856 patient samples (111% increase), 39 cancer types (39% increase) and 346 therapeutic regimens (26% increase), have been collected. In terms of function, for the single dataset analysis and multiple-dataset comparison modules, CTR-DB 2.0 added new gene set enrichment, tumor microenvironment (TME) and signature connectivity analysis functions to help elucidate drug resistance mechanisms and their homogeneity/heterogeneity and discover candidate combinational therapies. Furthermore, biomarker-related functions were greatly extended. CTR-DB 2.0 newly supported the validation of cell types in the TME as predictive biomarkers of treatment response, especially the validation of a combinational biomarker panel and even the direct discovery of the optimal biomarker panel using user-customized CTR-DB patient samples. In addition, the analysis of users’ own datasets, application programming interface and data crowdfunding were also added.

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Prostaglandin F_2α synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F_2α-dependent and F_2α-independent mechanism

Cited by 4 publications

References 42 publications

Does the Initial Treatment of the Primary Tumor Impact Prognosis after Recurrence in Locally Advanced Rectal Cancer? Results From A Retrospective Cohort Analysis

Does the Initial Treatment of the Primary Tumor Impact Prognosis after Recurrence in Locally Advanced Rectal Cancer? Results From A Retrospective Cohort Analysis

Does the initial treatment of primary tumor impact prognosis after recurrence in locally advanced rectal cancer? Results from a retrospective cohort analysis

CTR-DB 2.0: an updated cancer clinical transcriptome resource, expanding primary drug resistance and newly adding acquired resistance datasets and enhancing the discovery and validation of predictive biomarkers

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