Venetoclax for an ATRA and ATO resistance acute promyelocytic leukemia patient with TNRC18::RARA fusion gene.

Variant acute promyelocytic leukemia (APL) poses diagnostic and therapeutic challenges primarily because of the absence of PML::RARA. This report presents the case of a patient diagnosed with all-trans retinoic acid (ATRA)-resistant APL harboring the TNRC18::RARA fusion gene. After treatment with venetoclax, azacitidine, and ATRA, the patient achieved complete remission. The patient also developed pulmonary tuberculosis and a multidrug-resistant infection, which improved considerably after antituberculosis treatment and carrimycin, respectively.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

ETHE1 dampens colorectal cancer angiogenesis by promoting TC45 Dephosphorylation of STAT3 to inhibit VEGF-A expression.

Angiogenesis is critical for colorectal cancer (CRC) progression, but its mechanisms remain unclear. Here, we reveal that ethylmalonic encephalopathy protein 1 (ETHE1), an essential enzyme in hydrogen sulfide catabolism, inhibits VEGF-A expression and tumor angiogenesis in vitro and in vivo. Moreover, we find that this biological function of ETHE1 depends on the STAT3/VEGF-A pathway. Further investigation demonstrates that ETHE1 promotes the interaction between T cell protein tyrosine phosphatase (TC45) and STAT3, resulting in decreased STAT3 phosphorylation and inhibition of the STAT3 signaling pathway. In clinical samples, we find that ETHE1 is downregulated in CRC and positively correlates with survival outcomes of CRC patients. Meanwhile, the negative correlation of ETHE1 and VEGF-A expression is verified in CRC specimens, and the patients with low ETHE1 and high VEGF-A expression exhibits poorer prognosis. Collectively, our study identifies ETHE1 as a novel regulator of tumor angiogenesis, implying its potential as a prognostic biomarker and promising antiangiogenic target for CRC patients.

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.

Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that RPS19 exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56-0.83, P = 1.12 × 10-6), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene RPS19 mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of RPS19 during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.

Radiomics in cone-beam breast CT for the prediction of axillary lymph node metastasis in breast cancer: a multi-center multi-device study.

OBJECTIVES: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. METHODS: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. RESULTS: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). CONCLUSIONS: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. CLINICAL RELEVANCE STATEMENT: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. KEY POINTS: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node.

Inhibition of CARM1-Mediated Methylation of ACSL4 Promotes Ferroptosis in Colorectal Cancer.

Ferroptosis, which is caused by iron-dependent accumulation of lipid peroxides, is an emerging form of regulated cell death and is considered a potential target for cancer therapy. However, the regulatory mechanisms underlying ferroptosis remain unclear. This study defines a distinctive role of ferroptosis. Inhibition of CARM1 can increase the sensitivity of tumor cells to ferroptosis inducers in vitro and in vivo. Mechanistically, it is found that ACSL4 is methylated by CARM1 at arginine 339 (R339). Furthermore, ACSL4 R339 methylation promotes RNF25 binding to ACSL4, which contributes to the ubiquitylation of ACSL4. The blockade of CARM1 facilitates ferroptosis and effectively enhances ferroptosis-associated cancer immunotherapy. Overall, this study demonstrates that CARM1 is a critical contributor to ferroptosis resistance and highlights CARM1 as a candidate therapeutic target for improving the effects of ferroptosis-based antitumor therapy.

Radiomics nomogram for predicting axillary lymph node metastasis-a potential method to address the limitation of axilla coverage in cone-beam breast CT: a bi-center retrospective study.

PURPOSE: Cone-beam breast CT (CBBCT) has an inherent limitation that the axilla cannot be imaged in its entirety. We aimed to develop and validate a nomogram based on clinical factors and contrast-enhanced (CE) CBBCT radiomics features to predict axillary lymph node (ALN) metastasis and complement limited axilla coverage. MATERIAL AND METHODS: This retrospective study included 312 patients with breast cancer from two hospitals who underwent CE-CBBCT examination in a clinical trial (NCT01792999) during 2012-2020. Patients from TCIH comprised training set (n = 176) and validation set (n = 43), and patients from SYSUCC comprised external test set (n = 93). 3D ROIs were delineated manually and radiomics features were extracted by 3D Slicer software. RadScore was calculated and radiomics model was constructed after feature selection. Clinical model was built on independent predictors. Nomogram was developed with independent clinical predictors and RadScore. Diagnostic performance was compared among three models by ROC curve, and decision curve analysis (DCA) was used to evaluate the clinical utility of nomogram. RESULTS: A total of 139 patients were ALN positive and 173 patients were negative. Twelve radiomics features remained after feature selection. Location and focality were selected as independent predictors for ALN status. The AUC of nomogram in external test set was higher than that of clinical model (0.80 vs. 0.66, p = 0.012). DCA demonstrated that the nomogram had higher overall net benefit than that of clinical model. CONCLUSION: The nomogram combined CE-CBBCT-based radiomics features and clinical factors could have potential in distinguishing ALN positive from negative and addressing the limitation of axilla coverage in CBBCT.

Genetic Variants That Impact Alternative Polyadenylation in Cancer Represent Candidate Causal Risk Loci.

Alternative polyadenylation (APA) is emerging as a major mechanism of posttranscriptional regulation. APA can impact the development and progression of cancer, suggesting that the genetic determinants of APA might play an important role in regulating cancer risk. Here, we depicted a pan-cancer atlas of human APA quantitative trait loci (apaQTL), containing approximately 0.7 million apaQTLs across 32 cancer types. Systematic multiomics analyses indicated that cancer apaQTLs could contribute to APA regulation by altering poly(A) motifs, RNA-binding proteins (RBP), and chromatin regulatory elements and were preferentially enriched in genome-wide association studies (GWAS)-identified cancer susceptibility loci. Moreover, apaQTL-related genes (aGene) were broadly related to cancer signaling pathways, high mutational burden, immune infiltration, and drug response, implicating their potential as therapeutic targets. Furthermore, apaQTLs were mapped in Chinese colorectal cancer tumor tissues and then screened for functional apaQTLs associated with colorectal cancer risk in 17,789 cases and 19,951 controls using GWAS-ChIP data, with independent validation in a large-scale population consisting of 6,024 cases and 10,022 controls. A multi-ancestry-associated apaQTL variant rs1020670 with a C>G change in DNM1L was identified, and the G allele contributed to an increased risk of colorectal cancer. Mechanistically, the risk variant promoted aberrant APA and facilitated higher usage of DNM1L proximal poly(A) sites mediated by the RBP CSTF2T, which led to higher expression of DNM1L with a short 3'UTR. This stabilized DNM1L to upregulate its expression, provoking colorectal cancer cell proliferation. Collectively, these findings generate a resource for understanding APA regulation and the genetic basis of human cancers, providing insights into cancer etiology. SIGNIFICANCE: Cancer risk is mediated by alternative polyadenylation quantitative trait loci, including the rs1020670-G variant that promotes alternative polyadenylation of DNM1L and increases colorectal cancer risk.

Risk SNP in a transcript of RP11-638I2.4 increases lncRNA-YY1 interaction and pancreatic cancer susceptibility.

Tens of thousands of long non-coding RNAs (lncRNAs) have been identified through RNA-seq analysis, but the biological and pathological significance remains unclear. By integrating the genome-wide lncRNA data with a cross-ancestry meta-analysis of PDAC GWASs, we depicted a comprehensive atlas of pancreatic ductal adenocarcinoma (PDAC)-associated lncRNAs, containing 1,204 lncRNA (445 novel lncRNAs and 759 GENCODE annotated lncRNAs) and 4,368 variants. Furthermore, we found that PDAC-associated lncRNAs could function by altering chromatin activity, transcription factors, and RNA-binding proteins binding affinity. Importantly, genetic variants linked to PDAC are preferentially found at PDAC-associated lncRNA regions, supporting the biological and clinical relevance of PDAC-associated lncRNAs. Finally, we prioritized a novel transcript (MICT00000110172.1) of RP11-638I2.4 as a potential tumor promoter. MICT00000110172.1 is able to reinforce the interaction with YY1, which could reverse the effect of YY1 on pancreatic cancer cell cycle arrest to promote the pancreatic cancer growth. G > A change at rs2757535 in the second exon of MICT00000110172.1 induces a spatial structural change and creates a target region for YY1 binding, which enforces the effect of MICT00000110172.1 in an allele-specific manner, and thus confers susceptibility to tumorigenesis. In summary, our results extend the repertoire of PDAC-associated lncRNAs that could act as a starting point for future functional explorations, and the identification of lncRNA-based target therapy.

Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report.

Synchronous gastrointestinal multiple primary tumors including gastric, colonic, and rectal cancers are rare. Moreover, it was a challenge to find an appropriate procedure without negatively impacting the overall outcome. We described the case of a 63-year-old woman who presented with a 4 month history of upper abdominal pain, acid regurgitation, and anemia. Gastroscopy with biopsy suggested early cancer of gastric antrum. Abdominal contrast-enhanced computerized tomography and colonoscopy revealed ascending colon and rectum tumors. She had no family history of malignancy. Endoscopic submucosal dissection was performed for gastric cancer, and the pathological result presented that it was poorly differentiated and invaded into deep submucosa. The laparoscopy-assisted radical surgery combined with distal gastrectomy, right hemicolectomy, and anterior resection of rectum was performed for these three tumors via eight ports and a 7 cm midline upper-abdominal incision. No other perioperative complications were encountered except postoperative ileus. The patient was discharged on the 12th postoperative day. The pathological results revealed gastric cancer (T1N0M0), right colonic cancer (T3N1M0), and rectal cancer (T2N0M0), indicating complete surgical resection. We reported that our laparoscopic approach for synchronous triple primary gastrointestinal malignant tumors was feasible and minimally invasive.

Triclosan is associated with breast cancer via oxidative stress and relative telomere length.

Introduction: Triclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association. Methods: This case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells. Results: Significant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGF2α, RTL, and BC risk, with the odds ratios (95% confidence intervals) being 1.58 (1.32-1.91), 3.08 (1.55-6.23), 3.39 (2.45-4.77), 3.99 (2.48-6.54), and 1.67 (1.35-2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2α (all p<0.05) but not with 8-OHdG (p = 0.060) after adjusting for covariates. The mediated proportions of 8-isoPGF22α and RTL in the relationship between TCS and BC risk were 12.84% and 8.95%, respectively (all p<0.001). Discussion: In conclusion, our study provides epidemiological evidence to confirmed the deleterious effects of TCS on BC and indicated the mediating effect of oxidative stress and RTL on the correlation between TCS and BC risk. Moreover, exploring the contribution of TCS to BC can clarify the biological mechanisms of TCS exposure, provide new clues for the pathogenesis of BC, which is of great significance to improving public health systems.

Surgical and oncological outcomes of laparoscopic right hemicolectomy (D3 + CME) for colon cancer: A prospective single-center cohort study.

BACKGROUND: Complete mesocolic excision (CME) or D3 lymphadenectomy led to survival benefits for locally advanced right colon cancer, but with vague definitions in anatomy and debated surgical hazard in clinic. Aiming to achieve a precise definition of it in anatomy, we proposed laparoscopic right hemicolectomy (D3 + CME) as a novel procedure for colon cancer. However, the surgical and oncological results of this procedure in clinic were uncertain. METHODS: We performed a cohort study involving prospective data collected from a single-center in China. Data from all patients who underwent right hemicolectomy between January 2014 and December 2018 were included. We compared the surgical and oncological outcomes between D3 + CME and conventional CME. RESULTS: After implementation of exclusion criteria, a total of 442 patients were included. D3 + CME group performed better in lymph nodes harvested (25.0 [17.0, 33.8] vs. 18.0 [14.0, 25.0], P < 0.001) and the proportion of intraoperative blood loss ≥ 50 mL (31.7% vs. 51.8%, P < 0.001); no significant difference was observed in the complication rates between two groups. Kaplan-Meier analysis demonstrated that a better cumulative 5-year disease-free survival (91.3% vs. 82.2%, P = 0.026) and a better cumulative 5-year overall survival (95.2% vs. 86.1%, P = 0.012) were obtained in the D3 + CME group. Multivariate COX regression revealed that D3 + CME was an independent protective factor for disease-free survival (P = 0.026). CONCLUSION: D3 + CME could improve surgical and oncological outcomes simultaneously for right colon cancer compared to conventional CME. Large-scale randomized controlled trials were further required to confirm this conclusion, if possible.

Comparison of malignant calcification identification between breast cone-beam computed tomography and digital mammography.

BACKGROUND: Calcifications are important abnormal findings in breast imaging and help in the diagnosis of breast cancer. PURPOSE: To compare breast cone-beam computed tomography (CBCT) with digital mammography (DM) in terms of the ability to identify malignant calcifications. MATERIAL AND METHODS: In total, 115 paired examinations were performed utilizing breast CBCT and DM; 86 pathology-proven malignant lesions with calcifications detected on DM and 29 randomly selected breasts without calcifications were reviewed by three radiologists. The ability to detect calcifications was assessed on CBCT images. The characterization agreement of two imaging modalities was evaluated by the kappa coefficient. For breast CBCT images, the parameters for the display of calcifications were recorded. The Kruskal-Wallis test was used to compare the preferred slice thickness chosen by each of the three radiologists. The degree of calcification clarity was compared between two modalities using the Mann-Whitney U-test. RESULTS: The combined sensitivity and specificity of three radiologists in 85 DM-detected calcifications detection on breast CBCT images were 98.43% (251/255) and 98.85% (86/87), respectively. CBCT images showed substantial agreement with mammograms in terms of the characterization of calcifications morphology (k = 0.703; P < 0.05) and distribution (k = 0.629; P < 0.05). CBCT images with a slice thickness of 0.273 mm and three-dimensional maximum-intensity projection (3D-MIP) were more beneficial for calcifications identification. No statistically significant difference was found between standard DM views and CBCT images for three radiologists on calcification display clarity. CONCLUSION: CBCT images were comparable to mammograms in calcification identification and may be sufficient for malignant calcifications detection and characterization.

N-isopropylbenzylamine, a methamphetamine mimics, produces toxicity via increasing nitric oxide in vitro.

N-isopropylbenzylamine, an isomer of methamphetamine, has been used to adulterate methamphetamine, and distributed as fake "Ice" methamphetamine by illicit manufacturers, leading to a world problem of N-isopropylbenzylamine exposure. Though it is unclear whether N-isopropylbenzylamine has addictive potential like methamphetamine, N-isopropylbenzylamine users reported side effects such as headaches and confusion. However, the pharmacological targets and cytotoxicity of this chemical remained unknown. In this study, in vitro toxicity of N-isopropylbenzylamine and its toxicity-related targets were investigated in SN4741, SH-SY5Y or PC12 cell lines that model neurons. The cell viability was analyzed by using MTT assay after incubation with N-isopropylbenzylamine for 24 h in cells. N-isopropylbenzylamine caused cell death with IC50 values at around 1-3 mM in these cell lines. N-isopropylbenzylamine time- and concentration-dependently facilitated the expression of neuronal nitric oxide synthase (nNOS), and increased intracellular nitric oxide (NO) in SN4741 cells. Furthermore, 7-nitroindazole, a specific inhibitor of nNOS, significantly prevented N-isopropylbenzylamine-induced toxicity in vitro. These results suggested that N-isopropylbenzylamine-induced toxicity is at least partially related to the increased intracellular NO levels and the activated nNOS. Considering the circumstances that N-isopropylbenzylamine was used to adulterate and mimic methamphetamine, and the side effects associated with N-isopropylbenzylamine in abusers, our findings sounded an alarm for abuser and warn the dangerousness of N-isopropylbenzylamine for public health.

Dedicated breast CT: state of the art-Part II. Clinical application and future outlook.

Dedicated breast CT is being increasingly used for breast imaging. This technique provides images with no compression, removal of tissue overlap, rapid acquisition, and available simultaneous assessment of microcalcifications and contrast enhancement. In this second installment in a 2-part review, the current status of clinical applications and ongoing efforts to develop new imaging systems are discussed, with particular emphasis on how to achieve optimized practice including lesion detection and characterization, response to therapy monitoring, density assessment, intervention, and implant evaluation. The potential for future screening with breast CT is also addressed. KEY POINTS: • Dedicated breast CT is an emerging modality with enormous potential in the future of breast imaging by addressing numerous clinical needs from diagnosis to treatment. • Breast CT shows either noninferiority or superiority with mammography and numerical comparability to MRI after contrast administration in diagnostic statistics, demonstrates excellent performance in lesion characterization, density assessment, and intervention, and exhibits promise in implant evaluation, while potential application to breast cancer screening is still controversial. • New imaging modalities such as phase-contrast breast CT, spectral breast CT, and hybrid imaging are in the progress of R & D.

Dedicated breast CT: state of the art-Part I. Historical evolution and technical aspects.

Dedicated breast CT is an emerging 3D isotropic imaging technology for breast, which overcomes the limitations of 2D compression mammography and limited angle tomosynthesis while providing some of the advantages of magnetic resonance imaging. This first installment in a 2-part review describes the evolution of dedicated breast CT beginning with a historical perspective and progressing to the present day. Moreover, it provides an overview of state-of-the-art technology. Particular emphasis is placed on technical limitations in scan protocol, radiation dose, breast coverage, patient comfort, and image artifact. Proposed methods of how to address these technical challenges are also discussed. KEY POINTS: • Advantages of breast CT include no tissue overlap, improved patient comfort, rapid acquisition, and concurrent assessment of microcalcifications and contrast enhancement. • Current clinical and prototype dedicated breast CT systems differ in acquisition modes, imaging techniques, and detector types. • There are still details to be decided regarding breast CT techniques, such as scan protocol, radiation dose, breast coverage, patient comfort, and image artifact.

CCNI2 plays a promoting role in the progression of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan-Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence-activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan-Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2-siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.

Contrast-enhanced cone beam breast CT features of breast cancers: correlation with immunohistochemical receptors and molecular subtypes.

OBJECTIVES: To investigate the association of contrast-enhanced cone beam breast CT (CE-CBBCT) features, immunohistochemical (IHC) receptors, and molecular subtypes in breast cancer. METHODS: In this retrospective study, patients who underwent preoperative CE-CBBCT and received complete IHC results were analyzed. CE-CBBCT features were evaluated by two radiologists. Observer reproducibility and feature reliability were assessed. The association between CE-CBBCT features, IHC receptors, and molecular subtypes was analyzed using the chi-square, Mann-Whitney, and Kruskal-Wallis tests. Multivariate logistic regression was performed to assess the ability of combined imaging features to discriminate molecular subtypes. ROC curve was used to evaluate prediction performance. RESULTS: A total of 240 invasive cancers identified in 211 women were enrolled. Molecular subtypes of breast cancer were significantly associated with focality number of lesions, lesion type, tumor size, lesion density, internal enhancement pattern, degree of lesion enhancement (ΔHU), mass shape, spiculation, calcifications, calcification distribution, and increased peripheral vascularity of lesion (all p < 0.005), some of which also helped to differentiate IHC receptor status. A multivariate logistic regression model showed that tumor size (odds ratio, OR = 1.244), mass shape (OR = 0.311), spiculation (OR = 0.159), and internal enhancement pattern (OR = 0.227) were associated with differentiation between luminal and non-luminal subtypes (AUC = 0.809). Combined CE-CBBCT features, including lesion type (OR = 0.118), calcifications (OR = 0.181), and ΔHU (OR = 0.962), could be significant indicators of triple-negative versus HER-2-enriched subtypes (AUC = 0.913). CONCLUSIONS: CE-CBBCT features have the potential to help predict IHC receptor status and distinguish molecular subtypes of breast cancer, which could in turn help to develop individual treatment decisions and prognosis predictions. KEY POINTS: • A total of 11 CE-CBBCT features were associated with molecular subtypes, some of which also helped to differentiate IHC receptor status. • Tumor size, irregular mass shape, spiculation, and internal enhancement pattern could help identify luminal subtype. • Lesion type, calcification, and ΔHU could be significant indicators of HER-2- enriched versus triple-negative breast cancers.

Correction to: Cone-beam breast CT features associated with HER2/neu overexpression in patients with primary breast cancer.

The original version of this article, published on 03 January 2020, unfortunately contained two mistakes.