Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition.

N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.

Visual genetic typing of glioma using proximity-anchored in situ spectral coding amplification.

Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity-anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA mutations, enabling visual typing of brain gliomas with different pathological grades at the single-cell and tissue levels. The ligation-based padlock probe can discriminate one-nucleotide variations, and the design of proximity primers enables the anchoring of amplicons on target RNA, thus improving localization accuracy. The DNA module-based spectral coding strategy can dramatically improve the multiplexing capacity for imaging RNA mutations through one-time labelling, with low cost and simple operation. One-target-one-amplicon amplification confers ProxISCA the ability to quantify RNA mutation copy number with single-molecule resolution. Based on this approach, it is found that gliomas with higher malignant grades express more genes with high correlation at the cellular and tissue levels and show greater cellular heterogeneity. ProxISCA provides a tool for glioma research and precise diagnosis, which can reveal the relationship between cellular heterogeneity and glioma occurrence or development and assist in pathological prognosis.

One-Base-Gap Circular Probe-Mediated Dual Amplification for Isothermal Detection of N6-Methyladenosine Modifications.

N6-Methyladenosine (m6A) stands out as the predominant internal modification in mammalian RNA, exerting crucial regulatory functions in the metabolism of mRNA. Currently available methods have been limited by an inability to quantify m6A modification at precise sites. In this work, we screened a Bst 2.0 warm start DNA polymerase with the capability of discriminating m6A from adenosine (A) and developed a robust m6A RNA detection method that enables isothermal and ultrasensitive quantification of m6A RNA at single-base resolution. The detection limit of the assay could reach about 0.02 amol, and the quantitative accuracy of the assay was verified in real cell samples. Furthermore, we applied this assay to single-cell analysis and found that the coefficients of variation of the MALAT1 m6A 2611 site in glioblastoma U251 cells showed over 20% higher than in oligodendrocytes MO3.13 cells. This method provides a highly sensitive analytical tool for site-specific m6A detection and quantification, which is expected to provide a basis for precise disease diagnosis and epigenetic transcriptional regulation.

One Stone, Three Birds: Multifunctional Nanodots as "Pilot Light" for Guiding Surgery, Enhanced Radiotherapy, and Brachytherapy of Tumors.

Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.

Exploration of eMSCs with HA-GEL system in repairing damaged endometrium after endometrial cancer with fertility-sparing treatment.

Despite the high complete response rate of fertility-sparing treatment in early-stage endometrial cancer (EC), the low pregnancy rate is a clinical challenge. Whether endometrium-derived mesenchymal stem cells (eMSCs) can repair damaged endometrium after EC reversal remains unclear. This study explored the potential therapeutic effects of eMSCs with suitable scaffold materials on endometrial damage caused by EC. Here, appropriate engineering scaffold materials were compared to identify the most suitable materials to carry eMSCs. Then, safety and efficacy evaluations of eMSCs with a suitable hyaluronic acid hydrogel (eMSCs/HA-GEL) were investigated in in vivo experiments with subcutaneous xenotransplantation in Balb/C nude mice and a model of endometrial mechanical injury in rats. HA-GEL has minimal cytotoxicity to eMSCs compared to other materials. Then, in vitro experiments demonstrate that eMSCs/HA-GEL enhance the inhibitory effects of progestins on EC cell biological behaviors. eMSCs/HA-GEL significantly inhibit EC cell growth and have no potential safety hazards of spontaneous tumorigenesis in Balb/C nude mouse subcutaneous xenotransplantation assays. eMSCs/HA-GEL intrauterine transplantation effectively increases endometrial thickness and glandular number, improves endometrial blood supply, reduces fibrotic areas, and improves pregnancy rates in a rat endometrial mechanical injury model. GFP-eMSCs/HA-GEL intrauterine transplantation in rats shows more GFP-eMSCs in the endometrium than GFP-eMSCs transplantation alone, and no tumor formation or suspicious cell nodules are found in the liver, kidney, or lung tissues. Our results reveal the safety and efficacy of eMSCs/HA-GEL in animal models and provide preliminary evidence for the use of eMSCs/HA-GEL as a treatment for EC-related endometrial damage.

Minimal change disease with papillary thyroid carcinoma: a report of two adult cases.

BACKGROUND: Minimal change disease (MCD), a pathological type of nephrotic syndrome (NS), can occur in patients with tumors. We report two adult cases of MCD associated with papillary thyroid carcinoma (PTC), known to be extremely rare in adults. CASE PRESENTATION: A 35-year-old female patient was simultaneously diagnosed with MCD and PTC. The MCD was effectively treated with thyroidectomy and prednisone.In addition, a 50-year-old male patient, who had been diagnosed with PTC three years prior, had MCD confirmed by renal biopsy. The patient achieved complete remission following treatment with tacrolimus and rituximab. CONCLUSIONS: The present case report describes and discusses the diagnostic and treatment processes employed in these two patients. Clinicians need to be aware of the renal effects of treating patients with solid tumors.

The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth.

IscU2 is a scaffold protein that is critical for the assembly of iron-sulfur (Fe-S) clusters and the functions of Fe-S-containing mitochondrial proteins. However, the role of IscU2 in tumor development remains unclear. Here, we demonstrated that IscU2 expression is much higher in human pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent normal pancreatic tissues. In PDAC cells, activated KRAS enhances the c-Myc-mediated IscU2 transcription. The upregulated IscU2 stabilizes Fe-S cluster and regulates the activity of tricarboxylic acid (TCA) cycle enzymes α-ketoglutarate (α-KG) dehydrogenase and aconitase 2, which promote α-KG catabolism through oxidative and reductive TCA cycling, respectively. In addition to promoting mitochondrial functions, activated KRAS-induced and IscU2-dependent acceleration of α-KG catabolism results in reduced α-KG levels in the cytosol and nucleus, leading to an increase in DNA 5mC due to Tet methylcytosine dioxygenase 3 (TET3) inhibition and subsequent expression of genes including DNA polymerase alpha 1 catalytic subunit for PDAC cell proliferation and tumor growth in mice. These findings underscore a critical role of IscU2 in KRAS-promoted α-KG catabolism, 5mC-dependent gene expression, and PDAC growth and highlight the instrumental and integrated regulation of mitochondrial functions and gene expression by IscU2 in PDAC cells.

Colonic mucosal diffuse congestion associated with Osimertinib.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common histological subtype of lung cancer. Osimertinib has been recommended as first-line treatment of advanced NSCLC with EGFR mutations. Previous studies have only reported cases of gastrointestinal bleeding due to Erlotinib and gefitinib, but to date, always no cases of gastrointestinal bleeding due to Osimertinib have been reported. CASE REPORT: We report a case of a female patient with NSCLC with EFGR mutation. After 1.5 years of treatment with Osimertinib, a colonoscopy showed diffuse congestion of the colonic mucosa. MANAGEMENT AND OUTCOME: The patient's symptoms of blood in the stool disappeared, after stopping Osimertinib and giving mucosal protection treatment for 1 week. DISCUSSION: Osimertinib may have contributed to gastrointestinal bleeding because no recurrent bleeding was observed after discontinuation of treatment. Physicians and patients should be aware that osimertinib may increase the risk of gastrointestinal bleeding.

Roles of conserved active site residues in the IscS cysteine desulfurase reaction.

Escherichia coli cysteine desulfurase (CD), IscS, modifies basal metabolism by transferring sulphur (S) from L-cysteine to numerous cellular pathways, whereas NFS1, a human CD, is active only in the formation of the [Acp]2:[ISD11]2:[NFS1]2 complex. Despite the accumulation of red-coloured IscS in E. coli cells as a result of the deficiency of accessible iron, as revealed in our previous studies, the mechanism of the potential enzymatic reaction remains unclear. In this study, the N-terminus of IscS was fused with the C-terminus of NFS1, which was reported to be almost fully active as IscS and exhibits a pyridoxal 5'-phosphate (PLP) absorption peak at 395 nm. Moreover, SUMO-EH-IscS exhibited significant growth recovery and NADH-dehydrogenase I activity in the iscS mutant cells. Furthermore, through in vitro and in vivo experiments combined with high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry, it was shown that the new absorption peaks of the IscS H104Q, IscS Q183E, IscS K206A, and IscS K206A&C328S variants at 340 and 350 nm may correspond to the enzyme reaction intermediates, Cys-ketimine and Cys-aldimine, respectively. However, after mutation of the conserved active-site residues, additional absorption peaks at 420 and 430 nm were associated with PLP migration in the active-site pocket. Additionally, the corresponding absorption peaks of Cys-quinonoid, Ala-ketimine, and Ala-aldimine intermediates in IscS were 510, 325, and 345 nm, respectively, as determined by site-directed mutagenesis and substrate/product-binding analyses during the CD reaction process. Notably, red IscS formed in vitro by incubating IscS variants (Q183E and K206A) with excess L-alanine and sulphide under aerobic conditions produced an absorption peak similar to the wild-type IscS, at 510 nm. Interestingly, site-directed mutation of IscS with hydrogen bonds to PLP at Asp180 and Gln183 resulted in a loss of enzymatic activity followed by an absorption peak consistent with NFS1 (420 nm). Furthermore, mutations at Asp180 or Lys206 inhibited the reaction of IscS in vitro with L-cysteine (substrate) and L-alanine (product). These results suggest that the conserved active site residues (His104, Asp180, and Gln183) and their hydrogen bond with PLP in the N-terminus of IscS play a key role in determining whether the L-cysteine substrate can enter the active-site pocket and regulate the enzymatic reaction process. Therefore, our findings provide a framework for evaluating the roles of conserved active-site residues, motifs, and domains in CDs.

A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata.

BACKGROUND: HLRCC syndrome is a hereditary cancer predisposition syndrome caused by heterozygous germline pathogenic variant of the fumarate hydratase (FH) gene and characterized by cutaneous leiomyomas (CL), uterine leiomyomas (UL), and renal cell carcinoma (RCC). Loss of function variant of FH gene inactivates the Kreb's cycle enzyme activity and predisposes individuals with such variant to the development of HLRCC. METHODS: Next-generation sequencing (NGS) and Sanger confirmation were given to family members accessible. Following that, a functional study in vitro was performed to further confirm the pathogenicity of the variant. FH-Wild type (FH-WT) and FH-mutant (FH-MUT) (E378K) plasmid were constructed and transfected into 293T and uterine leiomyoma cell lines, respectively. Proliferation assessment was executed to show how this mutation affects the growth of uterine leiomyoma. qPCR and Western blotting were performed to investigate the change of transcription and translation of FH with mutation (E378K), and FH enzyme assay activity were tested in 293T cells with mutation and wild-type plasmids. RESULTS: Here, we presented two families with the same missense variant (c.1132G > A) that has not been reported as a germline mutation in hereditary uterine leiomyomas before and classified as VUS in gene databases. Our in vitro experiments supported the pathogenicity of this missense variant, especially in uterine leiomyomata. CONCLUSIONS: According to the American College of Medical Genetics (ACMG) guideline, the E378K variant was classified as likely pathogenic (with evidence PS4_support, PS3_support, PM2_support, PP1, PP3 and PP4 evidence). Further insights into clinical management in uterine leiomyomata were discussed and should be practiced in gynecological clinical settings.

Novel strategies for tumor radiosensitization mediated by multifunctional gold-based nanomaterials.

Radiotherapy (RT) is one of the most effective and commonly used cancer treatments for malignant tumors. However, the existing radiosensitizers have a lot of side effects and poor efficacy, which limits the curative effect and further application of radiotherapy. In recent years, emerging nanomaterials have shown unique advantages in enhancing radiosensitization. In particular, gold-based nanomaterials, with high X-ray attenuation capacity, good biocompatibility, and promising chemical, electronic and optical properties, have become a new type of radiotherapy sensitizer. In addition, gold-based nanomaterials can be used as a carrier to load a variety of drugs and immunosuppressants; in particular, its photothermal therapy, photodynamic therapy and multi-mode imaging functions aid in providing excellent therapeutic effect in coordination with RT. Recently, many novel strategies of radiosensitization mediated by multifunctional gold-based nanomaterials have been reported, which provides a new idea for improving the efficacy and reducing the side effects of RT. In this review, we systematically summarize the recent progress of various new gold-based nanomaterials that mediate radiosensitization and describe the mechanism. We further discuss the challenges and prospects in the field. It is hoped that this review will help researchers understand the latest progress of gold-based nanomaterials for radiosensitization, and encourage people to optimize the existing methods or explore novel approaches for radiotherapy.

Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma.

Endometrial cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states. Current models do not adequately reflect oncogenic origin and pathological progression in patients. Here we use single-cell RNA sequencing to profile cells from normal endometrium, atypical endometrial hyperplasia, and endometrioid endometrial cancer (EEC), which altogether represent the step-by-step development of endometrial cancer. We find that EEC originates from endometrial epithelial cells but not stromal cells, and unciliated glandular epithelium is the source of EEC. We also identify LCN2 + /SAA1/2 + cells as a featured subpopulation of endometrial tumorigenesis. Finally, the stromal niche and immune environment changes during EEC progression are described. This study elucidates the evolution of cell populations in EEC development at single-cell resolution, which would provide a direction to facilitate EEC research and diagnosis.

Image-guided interstitial brachytherapy for recurrent cervical cancer after radiotherapy: A single institution experience.

Purpose: The aim of this study is to evaluate the efficacy and toxicity of image-guided high-dose rate (HDR) interstitial brachytherapy (ISBT) for the reirradiation of cervical cancer within a previously irradiated area. Methods and materials: Twenty-three consecutive patients with cervical cancer were reirradiated with curative intent using brachytherapy (BT) with or without external beam irradiation. The median biologically equivalent dose in 2-Gy fractions (EQD2) for reirradiation was 64.0 Gy (range: 31.3-95.1 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 152.4 Gy (range: 97.8-200.9 Gy). The average clinical target volume was 82.9 cm3 (range: 26.9-208.3 cm3), and the median treatment-free interval (TFI) was 13 months (range: 3-93 months). Results: The median follow-up time was 19 months (range: 2-59 months). The complete response rate after reirradiation was 56.5%. The 1-, 2- 3-, and 4-year post-relapse survival (PRS) rates were 65.2%, 43.5%, 33.8%, and 27.1%, respectively. The median reirradiation EQD2 D2cc of rectum and bladder was 39.5 Gy (range = 14.6-96.2 Gy) and 52.1 Gy (range = 29.1-114.2 Gy). The median cumulative EQD2 D2cc of rectum and bladder was 115.0 Gy (range = 84.4-189.3 Gy) and 130.5 Gy (range = 95.5-173.5 Gy). During follow-up, nine (39.1%) patients had experienced grade 3 or 4 late toxicities. Grade ≥3 rectal toxicity occurred in three patients (13.0%). Grade ≥3 urinary toxicity occurred in five patients (21.7%). One patient (4.3%) had both grade ≥3 urinary and rectal toxicity. Tumor volume, TFI, tumor invasion organ number, and local control were significant prognostic factors adversely affecting OS. Conclusions: For recurrent cervical cancer after radiotherapy, reirradiation of HDR-ISBT is feasible, even if the local tumor invasion is large, with a good chance of survival and acceptable side effects.

Multimodality treatment for multiple recurrences of cervical cancer after radiotherapy: a case report.

Background: Despite the availability of multiple treatments, the prognosis of recurrent cervical cancer (RCC) remains poor. There are no reports of the entire treatment of cases with multiple recurrences, and clinicians have no guidelines in such cases. We share our experience and consider this complex case of multiple recurrences of cervical cancer. Case Description: We report our encounter with a challenging case of locally advanced cervical cancer with multiple recurrences after primary chemoradiotherapy. The first recurrence was a bulky lesion invading the posterior bladder wall and pelvic wall accompanied by severe haematuria and moderate anaemia. The patient was treated with various treatments during the course of the disease, including pelvic exenteration (PE), external beam radiotherapy (EBRT), radioactive seed implantation, and targeted therapy. These salvage treatments led to an overall survival (OS) of 47 months, a progression-free survival (PFS) after the last chemotherapy of 34 months, and a post-relapse survival of 13.5 months. However, the patient died from severe infection due to an intestinal fistula. Conclusions: This study reports on the experience of treatment after multiple relapses to provide a reference for clinicians. It suggests that PE should be considered for cervical cancer patients with central recurrence within the primary irradiated field when positive margins can be guaranteed, but it can be palliative even if the pelvic wall is invaded when no other treatments are available. Appropriate extension of resection or additional treatments such as intraoperative radiotherapy (IORT) and neoadjuvant chemotherapy can be considered for patients at high risk of re-recurrence.

Volumetric apparent diffusion coefficient (ADC) histogram metrics as imaging biomarkers for pretreatment predicting response to fertility-sparing treatment in patients with endometrial cancer.

OBJECTIVES: To investigate the feasibility of volumetric apparent diffusion coefficient (ADC) histogram analysis for prediction of fertility-sparing treatment (FST) response in patients with endometrial cancer (EC). METHODS: Pretreatment data of 54 EC patients with FST were retrospectively analyzed. Treatment response at each follow-up was pathologically evaluated. The associations of ADC histogram metrics (volume, minADC, maxADC, meanADC; 10th, 25th, 50th, 75th and 90th ADC percentiles; skewness; kurtosis) and baseline clinical characteristics with complete response (CR) at the second and third follow-ups, two-consecutive CR, and recurrence at the final follow-up were evaluated by uni- and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used for diagnostic performance evaluation. RESULTS: Compared with non-CR patients, CR patients had significantly higher minADC and 10th and 25th ADC percentiles at the second follow-up (P = 0.008, 0.039, and 0.034, respectively) and higher minADC, older age, lower HE4 level, and higher overweight rate at the third follow-up (P = 0.001, 0.040, 0.021, and 0.004, respectively). Patients with two-consecutive CR had a significantly higher minADC than those without (P = 0.018). There was no association between ADC metrics or clinical characteristics and recurrence (all P > 0.05). MinADC yielded the largest AUC in predicting CR (0.688 and 0.735 at the second and third follow-up, respectively) and the presence of two-consecutive CR (0.753). When combined with patient age and HE4 level, the prediction of CR could be further improved at the third follow-up, with an AUC of 0.786. CONCLUSION: Pretreatment minADC could be a potential imaging biomarker for predicting FST response. Clinical characteristics may have incremental value to minADC in predicting CR.

[Corrigendum] Silencing of RIPK4 inhibits epithelial­mesenchymal transition by inactivating the Wnt/ß­catenin signaling pathway in osteosarcoma.

Subsequently to the publication of the above article, the authors have realized that the same western blotting data shown for the vimentin bands for the U2OS cell line in Fig. 3B on p. 1159 had inadvertently been re­used for the ß­catenin bands for the U2OS cell line in Fig. 5A on p. 1161. The authors have re­examined their original data, and have realized that Fig. 5 was assembled incorrectly. The corrected version of Fig. 5, showing the correct ß­catenin bands for the U2OS cell line, is shown opposite. Note that this error did not quantitatively affect either the results or the overall conclusions reported in this paper. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a Corrigendum, and they apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 21: 1154­1162, 2020; DOI: 10.3892/mmr.2020.10939].

Volumetric ADC histogram analysis for preoperative evaluation of LVSI status in stage I endometrioid adenocarcinoma.

OBJECTIVES: To investigate the value of volumetric ADC histogram metrics for evaluating lymphovascular space invasion (LVSI) status in stage I endometrioid adenocarcinoma (EAC). METHODS: Preoperative MRI of 227 patients with stage I EAC were retrospectively analyzed. ADC histogram data were derived from the whole tumor with ROIs drawn on all slices of DWI scans (b = 0, 1000 s/mm2). The Student t-test was performed to compare ADC histogram metrics (minADC, maxADC, and meanADC; 10th, 25th, 50th, 75th, and 90th percentiles of ADC; skewness; and kurtosis) between the LVSI-positive and LVSI-negative groups, as well as between stage Ia and Ib EACs. ROC curve analysis was carried out to evaluate the diagnostic performance of ADC histogram metrics in predicting LVSI status in EAC. RESULTS: The minADC and meanADC and 10th, 25th, 50th, 75th, and 90th percentiles of ADC were significantly lower in LVSI-positive EACs compared with those in the LVSI-negative groups for stage I, Ia, and Ib EACs (all p < 0.05). MeanADC ≤ 0.857 × 10-3 mm2/s, meanADC ≤ 0.854 × 10-3 mm2/s, and the 90th percentile of ADC ≤ 1.06 × 10-3 mm2/s yielded the largest AUC of 0.844, 0.844, and 0.849 for evaluating LVSI positivity in stage I, Ia, and Ib tumors, respectively, with sensitivity of 75.4%, 75.0%, and 76.2%; specificity of 80.0%, 83.1%, and 82.1%; and accuracy of 79.3%, 81.5%, and 79.6%, respectively. CONCLUSION: Volumetric ADC histogram metrics might be helpful for the preoperative evaluation of LVSI status and personalized clinical management in patients with stage I EAC. KEY POINTS: • Volumetric ADC histogram analysis helps evaluate LVSI status preoperatively. • LVSI-positive EAC is associated with a reduction in multiple volumetric ADC histogram metrics. • MeanADC and the 90th percentile of ADC were shown to be best in evaluating LVSI- positivity in stage Ia and Ib EACs, respectively.