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Background: HER2-low breast cancers (BC) show a good response to novel anti-HER2 antibody-drug conjugates (ADCs) in advanced setting. Nevertheless, little is known about the response, category change, and prognosis of HER2-low BC receiving neoadjuvant treatment (NAT). Methods: Consecutive invasive BC patients who underwent ≥ 4 cycles of NAT and surgery from January 2009 to December 2020 were retrospectively reviewed. HER2-low was defined as IHC 1+ or 2+ and FISH negative. Concordance rates of HER2 and other biomarkers were analyzed by Kappa test. Kaplan–Meier analysis and Cox regression were used to assess the recurrence-free interval (RFI) and overall survival (OS). Results: A total of 2489 patients were included, of whom 1023 (41.1%) had HER2-low tumors. HER2-low patients had a higher ER positivity rate than HER2-0 patients (78.5% vs. 63.6%, P < 0.001), and a similar breast pathological complete response (pCR) rate (20.6% vs. 21.8%, P = 0.617). Among non-pCR cases, 39.5% of HER2-0 tumors changed to HER2-low, and 14.3% of HER2-low tumors changed to HER2-0 after NAT. Low concordance rates of HER2-low status were found in both ER-positive (Kappa = 0.368) and ER-negative (Kappa = 0.444) patients. Primary HER2-low patients had a significantly better RFI than HER2-0 patients (P = 0.014), especially among ER-positive subset (P = 0.016). Moreover, HER2-low category change was associated with RFI in ER-positive subset (adjusted P = 0.043). Conclusions: Compared with HER2-0 patients, HER2-low patients had a high proportion of ER-positive tumor and a similar pCR rate, which were related with better prognosis, especially in residual cases after NAT. A remarkable instability of HER2-low status was found between the primary and residual tumor, indicating re-testing HER2 status after NAT in the new era of anti-HER2 ADCs therapy. [ABSTRACT FROM AUTHOR]

Introduction: HER2‐low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor‐infiltrating lymphocytes (sTILs) in this population. Methods: Consecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2‐low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) negative. sTILs were scored following the international guidelines. Clinicopathologic features and survival were compared according to HER2 and sTILs category. Results: A total of 973 breast cancer patients were enrolled, including 615 (63.2%) HER2‐low patients. HER2‐low patients shared more similarity with HER2‐0 cases in clinicopathological features. sTILs in HER2‐Low patients was comparable to HER2‐0 patients (p = 0.064), both significantly lower than HER2‐positive ones (p < 0.001). Meanwhile, tumors with sTILs ≥50% accounted for the least proportion of HER2‐low cases (p < 0.001). HER2 status had no significant influence on recurrence‐free survival (RFS, p = 0.901) in the whole population. However, in the estrogen receptor (ER)‐negative subgroup, HER2‐low was related to worse RFS (p = 0.009) and OS (p = 0.001) compared with HER2‐positive ones. sTILs increment was an independent favorable prognostic factor in the whole (OS, p = 0.003; RFS, p = 0.005) and HER2‐low population (OS, p = 0.007; RFS, p = 0.009) after adjusted to clinicopathological parameters. Conclusions: HER2‐low patients shared similar clinicopathological features with HER2‐0 rather than HER2‐positive cases and had relatively low sTILs. ER‐negative/HER2‐low patients had significantly inferior survival. sTILs increment was independently associated with favorable survival in the HER2‐low group, suggesting a potential benefit from a novel treatment strategy. [ABSTRACT FROM AUTHOR]

Time interval between breast cancer (BC) diagnosis and surgery is of concern to patients and clinicians, but its impact on survival remains unclear. We identified 5130 BC patients receiving surgery between 2009 and 2017 from the Shanghai Jiaotong University Breast Cancer Database (SJTU-BCDB), and divided as Ruijin cohort and SJTU cohort. All participants were divided into three groups according to the interval between diagnosis and surgery: ≤ 1 week, 1–2 weeks, and > 2 weeks. Among 3144 patients of Ruijin cohort, the estimated 5-year breast cancer-free interval (BCFI) rates for the ≤ 1 week, 1–2 weeks and > 2 weeks groups were 91.8%, 87.5%, and 84.0% (P = 0.088), and the estimated 5-year overall survival (OS) rates were 95.6%, 89.6%, and 91.5% (P = 0.002). Multivariate analysis showed that patients with a TTS > 2 weeks had significantly lower BCFI (HR = 1.80, 95%CI 1.05–3.11, P = 0.034) and OS (HR = 2.07, 95% CI 1.04–4.13, P = 0.038) rates than patients with a TTS ≤ 1 week. Among 5130 patients when combining Ruijin cohort with SJTU cohort, the estimated 5-year BCFI rates for the ≤ 1 week, 1–2 weeks, and > 2 weeks groups were 91.0%, 87.9%, and 78.9%, and the estimated 5-year OS rates for the ≤ 1 week, 1–2 weeks, and > 2 weeks groups were 95.8%, 90.6%, and 91.5%, both with a significantly p value < 0.001. Our findings demonstrated the prolonged time to surgery (more than 2 weeks) after BC diagnosis was associated with poor disease outcomes, suggesting that efforts to early initiate treatment after diagnosis need to be pursued where possible to improve survival. [ABSTRACT FROM AUTHOR]

Ki67 would change after core needle biopsy (CNB) in invasive breast cancer. However, whether Ki67 alteration (ΔKi67) influences disease outcomes remains unclear. Here we aim to evaluate the prognostic value of ΔKi67. Patients with paired CNB and open excision biopsy (OEB) samples between January 2009 and June 2016 were retrospectively analyzed. ΔKi67 was calculated as the absolute difference between Ki67 level in CNB and OEB samples, and the median value of 5% was adopted to category patients into high- and low ΔKi67 groups. Disease-free survival (DFS) and overall survival (OS) were compared between different ΔKi67 groups. Overall, 2173 invasive breast cancer patients were included. Median Ki67 was higher in OEB than CNB samples: 25.00% versus 20.00% (P < 0.001). Axillary nodal status, STI, histological grading, and molecular subtype were independently associated with ΔKi67 (P < 0.05). In the whole population, patients with low ΔKi67 showed superior 5-year DFS (89.6% vs 87.0%, P = 0.026), but similar OS (95.8% vs 94.3%, P = 0.118) compared to those with high ΔKi67. HER2 status at surgery was the only significant factor interacting with ΔKi67 on both DFS (P = 0.026) and OS (P = 0.007). For patients with HER2-negative disease, high ΔKi67 was associated with worse 5-year DFS (87.2% vs 91.2%, P = 0.004) as well as impaired 5-year OS (93.9% vs 96.8%, P = 0.010). ΔKi67 had no significant impact on survival of HER2-positive patients. Ki67 increase after CNB was significantly associated with worse disease outcomes in HER2-negative, but not in HER2-positive patients, which warrants further study. [ABSTRACT FROM AUTHOR]

Pseudogene-derived transcripts, especially those barely transcribed in normal tissues, have been regarded as a kind of non-coding RNAs, and present potential functions in tumorigenicity and tumor development in human beings. However, their exact effects on hepatocellular carcinoma (HCC) remain largely unknown. On basis of our previous research and the constructed online database for the non-coding RNAs related to HCC, a series of pseudogene transcripts have been discovered, and SNRPFP1, the homologous pseudogene of SNRPF, was found to produce an anomalously high expression long non-coding RNA in HCC. In this study, we validated the expression of the SNRPFP1 transcript in both HCC tissues and cell lines. The adverse correlation between SNRPFP1 expression and patients' outcomes was observed. And depletion of SNRPF1 in HCC cells significantly suppressed cell proliferation and apoptosis resistance. Meanwhile, the motility of HCC cells was potently impaired. Interestingly, miR-126-5p, one of the tumor-suppressive genes commonly decreased in HCC, was found negatively expressed and correlated with SNRPF1, and a specific region of SNRPF1 transcript is directly binding to miR-126-5p in a molecular sponge way. The rescue experiment by knock-out miR-126-5p significantly reversed the cell growth suppression and a higher ratio of cell apoptosis induced by SNRPF1 depletion. Lastly, we concluded that SNRPF1 is a pseudogene active in HCC, and its abnormally over-expressed transcript is a strong promoter of HCC cell progress in vitro by sponging miR-126-5p. We believe that the findings in this study provide new strategies for HCC prevention and therapeutic treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Novel anti-HER2 antibody–drug conjugates showed convincing efficacy in HER2-Low breast cancer patients. We aimed to investigate the accuracy of core needle biopsy (CNB) in diagnosing HER2-Low status. We found a low concordance rate of HER2-Low status between CNB and surgical excision specimen (SES) samples in early-stage HER2-Negative patients. In tumors identified as HER2-0 by CNB, 50.3% expressed HER2 at any level at SES samples. Our research confirmed the necessity of retesting HER2-Low status in SES samples to guide precise anti-HER2 ADCs therapy. Background: HER2-Low status is found in approximately half of breast cancer patients and shows potential benefits from novel antibody–drug conjugates (ADCs). Data on the accuracy of HER2-Low status between core needle biopsy (CNB) and surgical excision specimen (SES) samples are lacking. We aimed to investigate the accuracy of HER2-Low status diagnosis between CNB and SES samples. Methods: Consecutive early-stage breast cancer patients who underwent surgery from January 2009 to March 2022 with paired CNB and SES samples were retrospectively reviewed. HER2-Low was defined as IHC 1+ or IHC2+ and FISH-negative. Concordance rates were analyzed by the Kappa test. Further clinicopathological characteristics were compared among different HER2 status and their changes. Results: A total of 5610 patients were included, of whom 3209 (57.2%) and 3320 (59.2%) had HER2-Low status in CNB and SES samples, respectively. The concordance rate of HER2 status in the whole population was 82.37% (Kappa = 0.684, p < 0.001), and was 76.87% in the HER2-Negative patients (Kappa = 0.372, p < 0.001). Among 1066 HER2-0 cases by CNB, 530 patients were classified as HER2-Low tumors. On the contrary, in 3209 patients with HER2-Low tumor by CNB, 387 were scored as HER2-0 on the SES samples. ER-negative or Ki67 high expression tumor by CNB had a high concordance rate of HER2-Low status. Conclusions: A relatively low concordance rate was found when evaluating HER2-Low status between CNB and SES samples in HER2-Negative breast cancer patients, indicating the necessity of retesting HER2 low status at surgery, which may guide further therapy in the era of anti-HER2 ADCs. [ABSTRACT FROM AUTHOR]

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy. Postmortem analyses provide useful information for COVID-19 etiology. Here the authors profile 22 deceased severe COVID-19 patients with transcriptomic and histological approaches to find correlations between the presence of viral antigens with lymphocyte suppression yet myeloid activation, hinting distinct functions of these cells during pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Patients and methods: Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival. Results: A total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre‐NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23–6.90, p < 0.001). Patients with high pre‐NAC TIL levels had a better 5‐year DFS than those with low pre‐NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31–0.81, p = 0.005). The multivariate analysis showed that pre‐NAC TIL (HR = 0.48; 95% CI = 0.29–0.81, p = 0.006) but not post‐NAC TIL (HR = 0.89, 95% CI = 0.50–1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre‐ and post‐NAC TIL levels had a worse 5‐year DFS than those with high pre‐NAC TIL levels (HR = 2.09, 95% CI = 1.23–3.56, p = 0.007). Conclusions: Pre‐NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre‐NAC TIL, and TIL category change, but not post‐NAC TIL, were significantly associated with DFS. [ABSTRACT FROM AUTHOR]

Background: It remains uncertain whether the 21-gene recurrence score (RS) of a primary tumor has selective prognostic value for locoregional recurrence (LRR) or distant metastasis (DM). The current study aimed to compare the distribution and single-gene expression on the RS panel in breast cancer patients with LRR versus DM. Methods: Consecutive early breast cancer patients who had been operated on at the Comprehensive Breast Health Center, Ruijin Hospital from January 2009 to December 2016 were retrospectively reviewed. Patients were divided into LRR, DM, and no-recurrence groups according to the first reported recurrent event. Comparison and subgroup analysis of 21-gene RS, RS category, and single-gene expression on the RS panel were conducted among patients with different recurrence status. Results: A total of 1,287 patients were included, with median follow-up of 61.5 months, and 27, 47, and 1,213 patients were classified as LRR, DM, and no recurrence groups, respectively. RS was significantly diversely distributed among the three groups (P< 0.001). No-recurrence patients (median 22) presented much lower RS than LRR (median 39, P< 0.001) and DM (median 30, P< 0.001) patients. LRR patients had lower PR (P< 0.001), BCL2 (P=0.010), and CEGP1 (P< 0.001) expression, and DM patients had higher STMY3 (P=0.019) expression than no-recurrence patients. Moreover, CEGP1 expression was significantly lower in the LRR group than the DM one (P=0.028). Conclusion: RS was differently distributed between recurrent and nonrecurrent patients. PR, BCL2, CEGP1, and STMY 3 expression was associated with LRR and DM, while CEGP1 was lower in the LRR group than DM patients, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease of the exocrine glands characterized by specific pathological features. Previous studies have pointed out that salivary glands from pSS patients express a unique profile of cytokines, adhesion molecules, and chemokines compared to those from healthy controls. However, there is limited evidence supporting the utility of individual markers for different stages of pSS. This study aimed to explore potential biomarkers associated with pSS disease progression and analyze the associations between key genes and immune cells. Methods: We combined our own RNA sequencing data with pSS datasets from the NCBI Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) via bioinformatics analysis. Salivary gland biopsies were collected from 14 pSS patients, 6 non-pSS patients, and 6 controls. Histochemical staining and scanning electron micrographs (SEM) were performed to macroscopically and microscopically characterize morphological features of labial salivary glands in different disease stages. Then, we performed quantitative PCR to validate hub genes. Finally, we analyzed correlations between selected hub genes and immune cells using the CIBERSORT algorithm. Results: We identified twenty-eight DEGs that were upregulated in pSS patients compared to healthy controls. These were mainly involved in immune-related pathways and infection-related pathways. According to the morphological features of minor salivary glands, severe interlobular and periductal lymphocytic infiltrates, acinar atrophy and collagen in the interstitium, nuclear shrinkage, and microscopic organelle swelling were observed with pSS disease progression. Hub genes based on above twenty-eight DEGs, including MS4A1, CD19, TCL1A, CCL19, CXCL9, CD3G, and CD3D, were selected as potential biomarkers and verified by RT-PCR. Expression of these genes was correlated with T follicular helper cells, memory B cells and M1 macrophages. Conclusion: Using transcriptome sequencing and bioinformatics analysis combined with our clinical data, we identified seven key genes that have potential value for evaluating pSS severity. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments. Patients and Methods: T1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)−; 2) HER2+; and 3) triple negative (TN) (HR−/HER2−). Patients' characteristics and relapse events were reviewed. Kaplan–Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models. Results: In total, 2,168 patients (1,435 HR+/HER2−, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2−, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11–2.84, P = 0.018] had a higher recurrence risk than HR+/HER2− patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68–7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95–5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005). Conclusion: Molecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC. [ABSTRACT FROM AUTHOR]

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents—findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Purpose: Given the histological special types (HST) of breast carcinoma accounted for minority of the Z0011 study population, this study aimed to assess the rates of axillary lymph node (ALN) involvement and non-sentinel lymph node (SLN) metastasis in patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or other HST. Methods: Patients with cT1-2N0M0 breast cancer treated between 2009 and 2018 were retrospectively included from a multi-institutional database. Rates of nodal involvement were analyzed among different histological subgroups. The impact of ALN dissection (ALND) on adjuvant treatment decisions and prognosis were also analyzed among patients with 1–2 + SLNs. Results: A total of 8294 patients were included: 6854 (82.6%), 257 (3.1%), and 1183 (14.3%) patients with IDC, ILC, and other HST, respectively. IDC patients had a significantly higher rate of ALN metastasis compared with ILC or other HST (31.9% vs. 22.6% vs. 16.4%, P < 0.001). However, in patients with 1–2 + SLNs, rates of non-SLN metastasis were similar among three groups (IDC: n = 182, 28.6% vs. ILC: n = 5, 31.2% vs. other HST: n = 29, 34.9%, P = 0.481). For patients with 1–2 + SLNs, rates of adjuvant chemotherapy and the estimated 3-year recurrence-free survival were similar between the SLN biopsy and ALND arms, regardless of the histological types. Conclusion: Among patients with 1–2 + SLNs, ILC or other HST had similar rates of non-SLN metastasis compared with IDC. Omission of ALND may not influence adjuvant chemotherapy usage or disease outcome regardless of histological types. [ABSTRACT FROM AUTHOR]

Pseudogenes exert potential functions in tumorigenicity and tumour process in human beings. In our previous research on oncogene AKR1B10 in hepatocellular carcinoma (HCC), its pseudogene, AKR1B10P1, was preliminarily noticed being anomalistic transcribed, whereas whether AKR1B10P1 plays any specific function in HCC is poorly understood. By using shRNA transfection and lentiviral infection, we regulated the expression of ARK1B10P1 transcript and the relative targets in two ways. As we discovered, pathological transcription of AKR1B10P1 in HCC cells significantly promotes cell growth and motility either in vitro or in vivo. AKR1B10P1 was correlated with relatively dismal features of HCC. The epithelial‐mesenchymal transition (EMT) was enhanced by up‐regulating AKR1B10P1. And, a potential sequence of AKR1B10P1 transcript was discovered directly interacting with miR‐138. SOX4, a pivotal promotor of EMT, was validated as the down‐streaming target of miR‐138. Mechanistically, degradation of SOX4 mRNA induced by miR‐138 was effectively abrogated by AKR1B10P1. In conclusion, pseudogene AKR1B10P1 exerts stabilizing effect on SOX4 in HCC, associated EMT process, by directly sponging miR‐138, which post‐transcriptionally modulates SOX4's regulating gene. [ABSTRACT FROM AUTHOR]

Background: Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Methods: Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). Results: The F2P Score was established by integrating the clinical (age and tumor size) and genomic (ESR1, PGR, BCL2, CD68, GSTM1 , and BAG1) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62–0.81) and BIC was 396.75 (95% CI, 252.37–541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87–4.61) or categorical (HR, 3.68; 95% CI, 1.70–8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. Conclusion: The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown. Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups. Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS. Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

In order to avoid penetrating shrinkage crack of massive concrete for main structure of cast-in-situ tunnel under Taihu Lake, a completed crack control scheme was proposed based on multi-field coupling crack resistance evaluation. Temperature rise and shrinkage deformation of tunnel concrete was double regulated by using a temperature rise inhibited and slight expansion admixture, both the average temperature drop rate of central concrete and temperature difference between inside and outside were remarkably reduced by using a novel self-adhesive heat and moisture insulating material, which was no more than 2.0 °C/d and 15 during temperature drop stage. The first massive sidewall was casted in November 2018, no sudden change was observed in deformation monitor curve and no crack was observed in entity structure till now, which means cracking control of cast-in-situ tunnel concrete achieved a good result. [ABSTRACT FROM AUTHOR]

Objectives: To explore the characteristics of breast ductal carcinoma in situ (DCIS) on real‐time grayscale contrast‐enhanced ultrasound (CEUS) imaging and the diagnostic value of CEUS in DCIS. Methods: A total of 127 histopathologically confirmed DCIS lesions and 124 fibroadenomas (FAs; controls) were subjected to conventional ultrasound and CEUS. Next, the CEUS findings of DCIS and FA lesions, including morphologic features and quantitative parameters, were analyzed. Results: Binary logistic regression was used to identify the independent risk factors from DCIS and FA lesions detected by CEUS. Contrast‐enhanced ultrasound revealed significant differences between DCIS and FA. The wash‐in time, enhancement mode, enhancement intensity, blood perfusion defects, peripheral high enhancement, enhancement scope, intratumoral vessels and their courses and dilatation degree, and penetrating vessels on CEUS were identified as features correlated with DCIS (P <.05). Moreover, a multivariate logistic regression analysis was developed, and the area under receiver operating characteristic curve of each index was generated, including the wash‐in time, enhancement intensity, blood perfusion defects, enhancement scope, penetrating vessels, arrival time, and peak intensity (P <.05; area under the curve, >0.6). Conclusions: The contrast‐enhancement patterns and DCIS parameters appeared different from FA lesions, thus suggesting that CEUS can be very useful in distinguishing DCIS from FA lesions. [ABSTRACT FROM AUTHOR]

NES1 gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in BCL-2 expression. The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an "enhanced firepower" effect by combining overexpressed NES1 gene therapy and 131I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing hNIS in PC3, the radioactive iodine uptake ability was significantly increased. Results of in vitro and in vivo tumor proliferation experiments and 18F-fluorothymidine (18F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined NES1 gene therapy and 131I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression. These data suggest that via inhibition of BCL-2 expression, overexpressed NES1 might enhance the effect of radiation therapy of 131I uptake in hNIS overexpressed PC3 cells. [ABSTRACT FROM AUTHOR]

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR+/HER2− patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58–152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90–6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42–145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39–1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR+/HER2− patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: There are limited data about how to manage patients with discordant hormonal receptor (HR) status between core needle biopsy (CNB) and following surgical sample (FSS). This study aimed to evaluate clinicopathological features and disease outcome for these HR discordance patients. Patients and Methods: Invasive breast cancer patients with paired HR between CNB and FSS were retrospectively analyzed, being classified into three groups: HR positive, HR negative, and HR discordance. Patient characteristics, treatment decisions, and disease outcome were compared among above groups. Results: A total of 1710 patients (1233 HR positive, 417 HR negative, and 60 HR discordance patients) were enrolled. Compared with the HR positive group, HR discordance patients were associated with more human epidermal growth factor receptor 2 positivity (P < 0.001) and higher Ki67 level (P = 0.001) tumors. The fraction of patients receiving adjuvant chemotherapy was 95.0% and 93.8% in the HR discordance or HR negative groups, much higher than in the HR positive group (66.7%, P < 0.001). Of 60 HR discordance patients, 34 (56.7%) received adjuvant endocrine therapy. The 5-year disease-free survival (DFS) rate was 90.4% for HR discordant patients, showing no statistical difference compared with HR positive (87.0%, P = 0.653) or HR negative (83.2%, P = 0.522) groups. For HR discordance patients, there was no difference in DFS between patients who received adjuvant endocrine therapy or not (P = 0.259). Conclusions: HR discordance patients had similar tumor characteristics, adjuvant chemotherapy treatment, and DFS compared with HR negative patients. The benefit of endocrine therapy in these HR discordance patients is uncertain and deserves further clinical evaluation. [ABSTRACT FROM AUTHOR]

SLC7A5, who is also named LAT-1, has been validated as a promoter regulated by miRNA-126 in our previous research for gastric cancer cells. However, the mechanisms driving SLC7A5 to affect the bio-function of gastric cancer cells are unclear, remaining us lots of to elucidate. The aim of this study is to investigate the regulating effect of CRKL, one of the critical genes involving with gastric cancer progression, on SLC7A5 expression. By studying the gastric cancer cell lines and clinical pathological specimens, we found that the expression of SLC7A5 was significantly correlated to CRKL. By depleting CRKL in gastric cancer SGC-7901 cells, the SLC7A5 expression was impaired, and the invasion and migration of SGC-7901 cells were suppressed. Ectopic expression of SLC7A5 could drastically rescue the phenotypes induced by CRKL depletion in this study. Accordingly, we conclude that SLC7A5 functions as a promoter in gastric cancer metastasis, and CRKL could be one of its regulators modulating the expression of SLC7A5 and consequentially affect the metastatic feature of SGC-7901 cells. The findings in this study indicate a regulation relationship between CRKL and SLC7A5, and provide useful evidence for gastric cancer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR. The optimal cutoff value was determined as 1.93 for NLR and the median follow-up time was 55.0 months. On univariate analysis, patients with high NLR (>1.93) had worse 5-year disease-free survival (DFS) compared to those with low NLR (77.9 vs 88.0 %, p = 0.002). Regarding overall survival, there was no significant difference between patients with high NLR and low NLR, with 5-year overall survival of 90.8 and 91.7 % ( p = 0.707). In triple-negative breast cancer, patients with high NLR was associated with worse 5-year DFS compared with patients with low NLR (63.4 vs 84.9 %, p = 0.040). Mutivariate analysis revealed that NLR was an independent prognostic factor for DFS in breast cancer (HR = 1.867, 95 % confidence interval; (95%CI) = 1.155-3.017, p = 0.011). Preoperative NLR is an independent predictor of DFS in breast cancer patients, especially in triple-negative subtype. Further studies are required to validate the prognostic value of NLR before clinical application. [ABSTRACT FROM AUTHOR]

Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum β-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration ( P = 0.0264 and P < 0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI). Methods: This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm2. Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed. Results: On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867×10-3 mm2/s and 0.732×10-3 mm2/s, respectively. Conclusion: Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma. [ABSTRACT FROM AUTHOR]

In non-pSS (Grade II), the duct structure of normal glands is clear, and ductal epithelial cells have full nuclei and are connected with myoepithelial cells by desmosomes. Primary Sjogren's syndrome (pSS), bioinformatics analysis, severity, transcriptome sequencing, potential biomarkers Keywords: primary Sjogren's syndrome (pSS); transcriptome sequencing; potential biomarkers; bioinformatics analysis; severity EN primary Sjogren's syndrome (pSS) transcriptome sequencing potential biomarkers bioinformatics analysis severity 1 2 2 10/01/21 20210929 NES 210929 In the original article, there was a mistake in the legends for B Figures 7 b , B Figure 8 b as published. [Extracted from the article]

Background: To investigate the accuracy of core needle biopsy (CNB) in evaluating breast cancer estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 status and to identify factors which might be associated with Ki67 value change after CNB.Methods: A retrospective study was carried out on 276 patients with paired CNB and surgically removed samples (SRS). Clinico-pathological factors as well as the surgery time interval (STI) between CNB and surgery were analyzed to determine whether there were factors associated with Ki67 value change after CNB. Five tumor subtypes were classified as follows: Luminal A, Luminal B-HER2-, Luminal B-HER2+, Triple Negative (TN), and HER2+. Ki67 value change was calculated as SRS minus CNB.Results: Mean STI after CNB was 4.5 (1-37) days. Good agreement was achieved for ER, PR, and HER2 evaluation between CNB and SRS. However, Ki67 expression level was significantly higher in SRS compared with CNB samples: 29.1 % vs. 26.2 % (P < 0.001). Both univariate and multivariate analysis demonstrated that STI and molecular subtype were associated with a Ki67 change after CNB. Luminal A tumors experienced more Ki67 elevation than Luminal B-HER2- diseases (6.2 % vs -0.1 %, P = 0.014). Patients with longer STI after CNB had a higher Ki67 increase: -1.1 % within 1-2 days, 2.1 % with 3-4 days, and 5.6 % more than 4 days, respectively (P = 0.007). For TN and HER2+ tumors, the Ki67 change was apt to be 0 with STI ≤ 4 days, while a >7 % Ki67 increase was noticed in patients with STI ≥ 5 days.Conclusion: CNB was accurate in evaluating ER, PR, HER2, and molecular subtype status. Ki67 value significantly increased after CNB, which was associated with STI and molecular subtype. Further translational research needs to consider Ki67 changes following CNB among different breast cancer molecular subtypes. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with a poor prognosis. The aim of our study was to identify biomarkers predictive of TNBC progression. Primary TNBC breast tissue samples including four with metastasis and six without metastasis were subjected to Affymetrix GeneChip® analysis (human genome U133). Ubiquitin-specific protease 2 (USP2) was identified as an upregulated gene in the metastatic group, and its expression was analyzed by immunohistochemistry in 121 primary breast cancers, 13 paired normal tissues, and 13 paired metastatic lesions. Survival analysis was performed using the log-rank test and Cox regression hazard model. Matrigel migration and invasion assays in USP2-silenced and USP2-overexpressed breast cancer cell lines were used to investigate the mechanisms of USP2 in vitro. Positive immunostaining for USP2 was detected in breast tumors and was correlated with estrogen receptor (ER) and progesterone receptor (PR) statuses and TNBC subtype. USP2 was overexpressed in distant metastatic lesions compared with primary breast cancers. Survival analyses demonstrated that positive USP2 is a poor prognostic factor for disease-free survival. Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2. The present study showed that USP2 expression is associated with TNBC cell line's invasiveness and poor survival of breast cancer patients and may serve as a prognostic biomarker and therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]

Background: The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure. Material and Methods: In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines. Results: Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line. Conclusions: Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making. Patients and Methods: A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors. Results: Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016). Conclusion: In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse. [ABSTRACT FROM AUTHOR]

The programmed death-1 (PD-1) molecule is mainly expressed on functionally 'exhausted' CD8 T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8 cytotoxic T lymphocytes, FOXP3 (Treg cell marker), and PD-1 immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1 immune cells and FOXP3 Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1 cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1 immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the capacity of magnetic resonance imaging (MRI) to distinguish breast cancer from inflammatory breast diseases manifesting as a rim-enhanced mass with central cystic changes. Materials and Methods: Forty cases of breast cancer and 52 of inflammatory breast diseases showing a rim-enhanced mass with central cystic changes were retrospectively reviewed. All cases underwent dynamic contrast-enhanced MRI and 31 of them underwent diffusion-weighted imaging (DWI). Morphological features, dynamic parameters and apparent diffusion coefficient (ADC) values were comparatively analyzed using univariate analysis and binary logistic regression analysis. Results: Breast cancer had a significantly thicker wall than the inflammatory breast diseases (P<0.001) while internal enhancing septa were more common in inflammatory breast diseases (P = 0.003). On DWI, 86.7% of breast cancers demonstrate a peripheral hyperintensity whereas 93.8% of inflammatory breast diseases had a central hyperintensity (P<0.001). Compared to the inflammatory breast diseases, breast cancers had a lower ADC value for the wall (1.09×10−3 mm2/s vs 1.42×10−3 mm2/s, P<0.001) and a higher ADC value for the central part (1.94×10−3 mm2/s vs 1.05×10−3 mm2/s, P<0.001). Conclusions: Both breast cancer and inflammatory breast diseases could present as a rim-enhanced mass with central cystic changes on MRI. Integrated analysis of the MR findings can allow for an accurate differential diagnosis. [ABSTRACT FROM AUTHOR]

Previous studies have reported that the aberrantly expressed AKR1B10 is associated with many cancer development, however the functional roles of AKR1B10 and its regulatory mechanisms in hepatocellular carcinoma (HCC) have been limited studied. In this project, we identified AKR1B10 functional as an oncogene in HCC through tumor/normal human tissue comparison from both GEO microarray and TCGA RNAseq dataset. Further experimental validations from three HCC cell lines (SMMC-7721, HePG2 and HeP3B) also suggested the ontogenetic functions of AKR1B10 in HCC tumor growth. By knocking down AKR1B10 through shRNA in HCC HeP3B cells, we showed it significantly induced cell cycle arrest and inhibited cell growth. Interestingly, integrative analysis of TCGA RNAseq data and miRNA-seq data predicted that miR-383-5p, a novel post-transcriptional tumor suppressor, is negatively associated with AKR1B10 expression. To further investigate the role of miR-383-5p in regulating AKR1B10 in HCC, we performed Dual-luciferase reporter assay experiments. Results showed that miR-383-5p is an upstream modulator targeting AKR1B10 in the post-transcriptional stage. Thus, we report AKR1B10 modulated regulated by miR-383-5p, promotes HCC tumor progress, and could be potentially a therapeutic target for precision medicine in HCC. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/ncomms15533 [ABSTRACT FROM AUTHOR]

The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOPP94R, EZH1Q571R and ZNF148 mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) can promote cancer initiation and progression by releasing cytokines. Previously, we have found the density of TAMs correlated with lymph node metastasis in papillary thyroid carcinoma (PTC). However, the mechanisms of how TAMs promote PTC progression remain unclear. In this study, we first showed that the TAMs density in the tumor core was associated with progressive PTC features and TAMs conditioned medium enhanced PTC cells invasion. Cytokine profiling identified a mixed M1/M2 phenotype and CXCL8 was the most consistently abundant cytokine in PTC-derived TAMs. CXCL8 receptors, CXCR1 and CXCR2, were positively stained in PTC cell lines and tissues, though no association with lymph node metastasis or extrathyroid extension. PTC cell invasion was abrogated by anti-CXCL8-neutralizing antibody, whereas addition of exogenous recombinant human CXCL8 enhanced the invasiveness. More importantly, CXCL8 promoted PTC metastasis in vivo. No difference was found for TAMs-derived CXCL8 expression in patients with and without lymph node metastasis or extrathyroid extension. These findings indicated that TAMs may facilitate PTC cell metastasis through CXCL8 and its paracrine interaction with CXCR1/2.We found TAMs may facilitate metastasis of PTC cell through CXCL8 and its paracrine interaction with CXCR1/2. Our findings indicated an important role of the interaction between cancer cell and its microenvironment in thyroid cancer progression. [ABSTRACT FROM AUTHOR]

Background: Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented.Methods: Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.Results: There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (κ = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB.Conclusion: CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors. [ABSTRACT FROM AUTHOR]