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The treatment strategies for T1 oesophageal squamous cell carcinoma (ESCC) patients with or without lymph node metastasis (LNM) are different. Given the advantages of the minimally invasive, sensitive and real-time detection, liquid biopsy has become an important cancer diagnostic and prognostic tool.MiRNA array and small-RNA sequencing were performed. Then, 222 formalin-fixed and paraffin-embedded tumour samples and 229 pretreatment serum samples from T1 ESCC patients were used to verify and evaluate the results.We demonstrated that serum miR-20b-5p could predict LNM in T1 ESCC patients. The AUC for serum miR-20b-5p was higher (0.827) than those for lymphovascular invasion (LVI) (0.751, P = 0.2128), invasion depth (0.662, P = 0.0027) and tumour differentiation grade (0.634, P = 0.0019). A nomogram for predicting LNM with three independent significant predictors (miR-20b-5p, LVI and invasion depth) was constructed with a concordance index of 0.931. Serum miR-20b-5p was also significantly correlated with disease-free survival (P 0.001). An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level was constructed.This study suggests that serum miR-20b-5p is a potential biomarker for predicting LNM and can be helpful for precise clinical decision-making strategies and improve treatment outcomes for T1 ESCC patients.

Gastric adenocarcinoma (GA) is a heterogeneous tumor, and the accurate classifications are important. Previous classifications are based on molecular analysis and neglect GA with the primitive enterocyte phenotype (GAPEP), a unique subtype with a poor prognosis and frequent liver metastases. New substituted molecular (SM) classifications based on immunohistochemistry (IHC) are needed. According to the IHC staining results, we divided 582 cases into six types: mismatch repair deficient (dMMR), Epstein-Barr virus associated (EBVa), the primitive enterocyte phenotype (PEP), the epithelial mesenchymal transition (EMT) phenotype, not other special/P53 mutated (NOS/P53m) and not other special/P53 wild-type (NOS/P53w). We analyzed the clinicopathological features, immune microenvironment (PD-L1, CD8) and expression of HER2 and VEGFR2 of those types. There were 31 (5.3%) cases of the dMMR type, 13 (2.2%) cases of the EBVa type, 44 (7.6%) cases of the PEP type, 122 (21.0%) cases of the EMT type, 127 (21.8%) cases of the NOS/P53m type and 245 (42.1%) cases of the NOS/P53w type. Patients with the dMMR type had the best survival (P

Background Lymphovascular invasion (LVI) is a crucial predictor of lymph node metastasis (LNM). However, few studies have investigated the LVI positivity rate and its clinical significance in pT1b esophageal squamous cell carcinoma (ESCC) using immunohistochemistry and elastin staining. Methods We collected data from158 patients with pT1b ESCC who had undergone radical esophagectomy. All paraffin blocks of invasive carcinoma from each patient were subjected to HE staining, elastin staining + CK (AE1/AE3) immunohistochemistry (E&IHC), and CD31/D2-40 + CK (AE1/AE3) double immunohistochemistry (D-IHC). The LVI was classified into types, i.e., vascular invasion (VI) and lymphatic vessel invasion (LI), and its location, quantity, and clinical significance were explored. Results The positivity rates of VI by E&IHC (E-VI), VI by CD31D-IHC (CD31-VI), and LI by D2-40 D-IHC (D2-40-LI) were significantly higher than those obtained by HE staining (P Conclusion E&IHC and D-IHC can dramatically improve the detection rate of LVI in pT1b ESCC, and the classification and grading of LVI can help to improve the prediction of LNM and prognosis.

AimTo compare the long-term nutritional status, reflux esophagitis and anastomotic stenosis, between total gastrectomy (TG) and proximal gastrectomy (PG).MethodsPatients who underwent PG or TG in this single institution between January 2014 and December 2016 were included in this study. The inclusion and exclusion criteria were defined. One-to-one propensity score matching (PSM) by the demographic and pathological characteristics was performed to compare the long-term outcomes between the two groups. The primary endpoint was long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes.ResultsTotally 460 patients received PG or TG in our institution for the treatment between January 2014 and December 2016 and according to the inclusion and exclusion criteria 226 cases were included in this study finally. There was no significant difference as to nutritional status in the end of first 5 years after PG or TG. While reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group (54.4% versus 26.8%, p < 0.001; 14.9% versus 4.5%, p=0.015; respectively). Overall survival rates were similar between the two groups after PSM (5-year survival rates: 65.4% versus 61.5% in the PG and TG groups, respectively; p = 0.54). The rate of carcinoma of remnant stomach after PG was 3.5% in this group of patients.ConclusionsTG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG.

The impact of neoadjuvant chemotherapy (NAC) on patients with neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the stomach is unclear. The aim of this retrospective study was to evaluate the effects of NAC on patients with these conditions. This study included patients with locally advanced NEC or MANEC of the stomach who underwent gastrectomy. Histologic and prognostic effects of NAC were assessed. The overall survival (OS) rate was used to compare treatment efficacies between NAC patients and surgery-first patients. Of the 69 patients included in this study, 20 received NAC and 49 underwent surgery first after diagnosis. A total of 13 patients responded to NAC (including 3 with complete remission and 10 with partial remission) and 7 patients acquired stable disease status according to the Response Evaluation Criteria in Solid Tumors version 1.1. One patient (5%) achieved a pathological complete response after NAC. Pathological tumor regression grades 1, 2, 3, 4, and 5 were observed in 1 (5%), 5 (25%), 3 (15%), 10 (50%), and 1 (5%) patient(s) with NAC, respectively. The incidence of postoperative complications was similar in the two groups. Patients in the NAC group demonstrated better OS than did patients in the surgery-first group (P = 0.032). Multivariate analyses showed that NAC, adjuvant chemotherapy, and the clinical N stage were independent factors affecting OS. In patients with locally advanced NEC and MANEC of the stomach, NAC significantly improved OS.

Purpose: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression. Experimental Design: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells. Results: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell–formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo. Conclusions: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.

BackgroundThis study aimed to explore the predictive value of quantitative dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters for the response to neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) patients, and the relationship between the prediction results and patients’ prognosis, so as to provide a basis for clinical individualized precision treatment.MethodsOne hundred twenty-nine newly diagnosed LAGC patients who underwent IVIM-DWI and DCE-MRI pretreatment were enrolled in this study. Pathological tumor regression grade (TRG) served as the reference standard of NCT response evaluation. The differences in DCE-MRI and IVIM-DWI parameters between pathological responders (pR) and pathological non-responders (pNR) groups were analyzed. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCT response. Prediction models were built with statistically significant quantitative parameters and their combinations. The performance of these quantitative parameters and models was evaluated using receiver operating characteristic (ROC) analysis. Clinicopathological variables, DCE-MRI and IVIM-DWI derived parameters, as well as the prediction model were analyzed in relation to 2-year recurrence-free survival (RFS) by using Cox proportional hazards model. RFS was compared using the Kaplan–Meier method and the log-rank test.ResultsSixty-nine patients were classified as pR and 60 were pNR. Ktrans, kep, and ve values in the pR group were significantly higher, while ADCstandard and D values were significantly lower than those in the pNR group. Multivariate logistic regression analysis demonstrated that Ktrans, kep, ve, and D values were independent predictors for NCT response. The combined predictive model, which consisted of DCE-MRI and IVIM-DWI, showed the best prediction performance with an area under the curve (AUC) of 0.922. Multivariate Cox regression analysis showed that ypStage III and NCT response predicted by the IVIM-DWI model were independent predictors of poor RFS. The IVIM-DWI model could significantly stratify median RFS (52 vs. 15 months) and 2-year RFS rate (72.3% vs. 21.8%) of LAGC.ConclusionPretreatment DCE-MRI quantitative parameters Ktrans, kep, ve, and IVIM-DWI parameter D value were independent predictors of NCT response for LAGC patients. The regression model based on baseline DCE-MRI, IVIM-DWI, and their combination could help RFS stratification of LAGC patients.

Circular RNAs (circRNAs) regulate gene expression by acting as a 'sponge' for microRNAs (miRs) and play crucial roles in tumorigenesis, including in bladder cancer (BC). circRNA‑baculoviral IAP repeat‑containing 6 (circ‑BIRC6) has been reported to participate in the pathogenesis of several cancer types. The present study aimed to elucidate the roles and potential mechanisms of circ‑BIRC6 in the progression of BC. circ‑BIRC6 expression levels in BC cell lines were determined using reverse transcription‑quantitative PCR. Following circ‑BIRC6 knockdown, cell proliferation, invasion and migration were detected using Cell Counting Kit‑8, colony formation, Transwell and wound healing assays, respectively. Western blotting was also conducted to evaluate the expression levels of X‑box binding protein 1 (XBP1) and epithelial‑mesenchymal transition (EMT)‑associated proteins. In addition, rescue experiments were performed using by transfecting a miR‑495‑3p inhibitor into T24 cells following circ‑BIRC6 knockdown. The interactions between circ‑BIRC6, miR‑495‑3p and XBP1 was verified using dual luciferase reporter assays. Moreover, T24 cells with circ‑BIRC6 knockdown and miR‑495‑3p inhibitor transfection were used for the tumor‑bearing experiment. Tumor growth was observed and Ki‑67 expression was determined using immunohistochemistry. The results demonstrated that circ‑BIRC6 expression was upregulated in BC cell lines. Moreover, circ‑BIRC6 knockdown notably attenuated the proliferation, invasion, migration and EMT of BC cells, which was blocked by the miR‑495‑3p inhibitor. It was also identified that circ‑BIRC6 sponged miR‑495‑3p to regulate XBP1 expression. In addition, results from the xenograft experiments indicated that the knockdown of circ‑BIRC6 and miR‑495‑3p expression significantly inhibited tumor growth. It was also found that the expression levels of XBP1, Ki‑67 and EMT‑associated proteins in tumor tissues of the co‑transfection group were markedly restored compared with the circ‑BIRC6 knockdown group. In conclusion, these findings demonstrated that circ‑BIRC6 knockdown suppressed BC tumorigenesis and progression via regulation of the miR‑495‑3p/XBP1 signaling axis, offering a promising therapeutic target for the treatment of BC.

e16001 Background: PD-1 inhibitor combined with chemotherapy showed remarkable objective response rate in the first line treatment of metastatic gastric cancer. While, the benefit of perioperative PD-1 inhibitor plus chemotherapy in locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer was not clear. Therefore, we aimed to assess the efficacy and safety of perioperative XELOX plus toripalimab in the patients with locally advanced G/GEJ cancer in this study. Methods: This was a prospective single arm phase 2 study. Eligible patients were with histologically confirmed locally advanced G/GEJ (Siewert II/II type) adenocarcinoma (cT3-4 Nany M0 or T1-2 N2-3 M0). Patients received 4 preoperative and 2 postoperative cycles of XELOX plus toripalimab (oxaliplatin 130mg/m2 D1, capecitabine 1000mg/m2 bid D1-14, toripalimab 240mg D1, Q3W) followed by subsequent 2 cycles of toripalimab monotherapy. Patients underwent D2 gastrectomy after preoperative treatment. The primary endpoint was major pathological response (MPR) according to Becker TRG criteria. Secondary endpoints included safety, R0 resection rate, pathological complete response (pCR), 3-year disease free survival (DFS) and 3-year overall survival (OS). Results: From Jul, 2019, to Dec, 2021, 35 pts were recruited. The median age was 61 (34-72) years old. 80% of the pts were men. Acutally, all the pts had cT4 (cT4a [48.6%] & cT4b [51.4%]) and 88.6% had cN+ by CT, MRI and ultrasound gastroscopy. 2 pts suffered disease progression during neoadjuvant treatment. 4 pts have not yet completed preoperative therapy. 29 pts had received gastrectomy and 2 pts were pathologically diagnosed with large cell neuroendocrine carcinoma. Therefore, 27 adenocarcinoma pts were included in this analysis. 3 (11.1%) pts achieved pCR (TRG1a) and 4 (14.8%) pts achieved MPR (TRG1a/b). R0 resection was achieved in 96.3% (26/27) of the pts. No patient had pT4b. The most common (≥10%) grade 1-2 treatment related adverse events (TRAEs) included leucopenia (45.7%), neutropenia (42.9%), thrombocytopenia (20%), nausea (34.1%), vomiting (14.3%), anorexia (14.3%), ALT increased (40%) and AST increased (34.3%). Only 4 (11.4%) pts experienced grade 3 neutropenia. No other ≥ grade 3 TRAEs occurred. Most of the potential immune-related adverse events were grade 1-2 including hypothyroidism (8.6%), adrenal insufficiency (2.9%) and hyperglycemia (11.4%). Only one (2.9%) patient had grade 3 hyperglycemia. No serious perioperative complication and death occurred. Conclusions: Perioperative XELOX plus toripalimab preliminarily showed a favorable R0 resection rate and acceptable MPR in cT4a/T4b locally advanced G/GEJ cancer patients with a manageable safety profile. Clinical trial information: NCT04119622.

Background Aging is a comorbidity of breast cancer suggesting that aging-associated transcriptome changes may promote breast cancer progression. However, the mechanism underlying the age effect on breast cancer remains poorly understood. Method We analyzed transcriptomics of the matched normal breast tissues from the 82 breast cancer patients in The Cancer Genome Atlas (TCGA) dataset with linear regression for genes with age-associated expression that are not associated with menopause. We also analyzed differentially expressed genes between the paired tumor and non-tumor breast tissues in TCGA for the identification of age and breast cancer (ABC)-associated genes. A few of these genes were selected for further investigation of their malignancy-regulating activities with in vitro and in vivo assays. Results We identified 148 upregulated and 189 downregulated genes during aging. Overlapping of tumor-associated genes between normal and tumor tissues with age-dependent genes resulted in 14 upregulated and 24 downregulated genes that were both age and breast cancer associated. These genes are predictive in relapse-free survival, indicative of their potential tumor promoting or suppressive functions, respectively. Knockdown of two upregulated genes (DYNLT3 and P4HA3) or overexpression of the downregulated ALX4 significantly reduced breast cancer cell proliferation, migration, and clonogenicity. Moreover, knockdown of P4HA3 reduced growth and metastasis whereas overexpression of ALX4 inhibited the growth of xenografted breast cancer cells in mice. Conclusion Our study suggests that transcriptome alterations during aging may contribute to breast tumorigenesis. DYNLT3, P4HA3, and ALX4 play significant roles in breast cancer progression.

The current clinical standard for mass screening of prostate cancer are prostate-specific antigen (PSA) biomarker assays. Unfortunately, the low specificity of PSA's bioassays to prostate cancer leads to high false-positive rates, as such there is an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we have successfully demonstrated, with the use of our Photonic-Crystal based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, detection of prostate cancer (PC-3) cells against benign prostate hyperplasia (BPH-1) cells. The PC-TIR biosensor achieved detection of individual prostate cancer cells utilizing cellular refractive index (RI) as the only contrast parameter. To further study this methodology in vitro, we report a comprehensive study of the cellular RI's of various prostate cancer and noncancerous cell lines (i.e. RWPE-1, BPH-1, PC-3, DU-145, and LNCaP) via reflectance spectroscopy and single-cell RI imaging utilizing the PC-TIR biosensor. Our study shows promising clinical potential in utilizing the PC-TIR biosensor system for the detection of prostate cancer against noncancerous prostate epithelial cells.

Glioma-associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration-resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen-responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen-dependent and -independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re-expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.

e21607 Background: The mutational profile of non-small cell lung cancer (NSCLC) has been widely studied. However, the correlation between mutational profile and the prognosis of various molecular subtypes of NSCLC has not been fully investigated. Methods: We established the mutational landscape from 244 stage I-IV NSCLC patients using a 605-gene next generation sequencing panel. Molecular subtyping was performance based on the mutational status of EGFR, TP53, KRAS and STK11 genes according to reported methods. Sequencing data were analyzed with R packages and statistics analysis was performed with Graphpad PRISM 5.0 software. P ≤ 0.05 was regarded as statistically significant. Results: Differential SNV/INDEL mutation frequency across stage I-IV was found in EGFR, TP53, ATM, CDKN2A and NF1 (P < 0.05), differential CNV frequency was found in EGFR, RB1, PIK3CA, TERT, KRAS, FGFR1 and ERBB2 (P < 0.05), and differential SV frequency was found in ROS1 (P < 0.05). TMB of stage III-IV patients was higher than those of stage I (P < 0.05). TMB was higher in patients with TP53 but without EGFR mutations (P < 0.05). The association between prognosis and mutational status was further investigated in stage IV NSCLC. Patients with EGFR SNV/INDEL mutations exhibited better PFS and OS time, while patients with KRAS and/or STK11 SNV/INDEL mutations, or without mutations in EGFR, TP53, KRAS and STK11 exhibited worse PFS and OS time. However, no significant difference was observed in PFS and OS between patients with or without TP53 SNV/INDEL, EGFR CNV, ERBB2 CNV or TERT CNV variations. Further analysis showed that male or age≥62 exhibited worse OS time (P < 0.05), while smoking history, palliative surgery and palliative radiotherapy did not affect the PFS and OS time of stage IV patients. Conclusions: We found differential frequency in SNV/INDEL, CNV and SV variations across stage I-IV NSCLC. EGFR SNV/INDEL, KRAS SNV/INDEL, STK11 SNV/INDEL mutation, gender and age were found to be prognostic predicting factors for stage IV NSCLC.

Background Programmed death ligand 1 (PD-L1) is a ligand for the inhibitory programmed cell death protein 1 (PD-1), which are targeted by several anti-PD-1 and PD-L1 drugs for a variety of human cancers. However, only a few studies have evaluated PD-L1 expression in esophageal squamous cell carcinoma (ESCC) with a large Chinese cohort. Our present study is to evaluate the association of PD-L1 expression with clinicopathological features on ESCC. Methods Using tissue microarray and immunohistochemistry, PD-L1 expression on tumor cells and tumor-infiltrating immune cells was studied in 378 advanced ESCC patients without neoadjuvant chemoradiotherapy. Its correlation with clinicopathological parameters was analyzed. Results PD-L1 was expressed on 29.9% (113/378) ESCC tumor cells and 40.2% (152/378) tumor-infiltrating immune cells. PD-L1 expression in tumor cells was significantly correlated with age, degree of differentiation, T stage, N stage and metachronous hematogenous metastasis, and PD-L1 expression in tumor-infiltrating immune cells was significantly associated with N stage (P

Breast cancer treatment options often include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, we utilized a fiber-optic probe to characterize in vivo HER2 and EGFR overexpressed tumors through the fluorescence of targeted dyes. HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. The fiber was inserted into the samples via a 30-gauge needle. Different wavelengths of a supercontinuum laser were selected to couple into the fiber and excite the corresponding fluorophores in the samples. The fluorescence from the dyes was collected through the same fiber and quantified by a time-correlated single photon counter. Fluorescence at different antibody-dye concentrations was measured for calibration. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates and were later probed at the tumor sites. The measured fluorescence was used to distinguish between tumor types and to calculate the concentration of the antibody-dye conjugates, which were detectable at levels as low as 40 nM. The fiber-optic probe presents a minimally invasive instrument to characterize the molecular signatures of breast cancer in vivo.

Advanced, recurrent, or persistent cervical cancer is often incurable. Therefore, in-depth insights into the molecular mechanisms are needed for the development of novel therapeutic targets and the improvement of current therapeutic strategies. In this study, we investigated the role of GLI2 and GLI3 in the regulation of the malignant properties of cervical cancer. We showed that down-regulation of GLI2, but not GLI3, with an inducible GLI2 shRNA inhibited the growth and migration of cervical cancer cell lines, which could be rescued by ectopic expression of GLI2. GLI2 appeared to support cell growth by regulating the mitosis, but not the apoptosis, of the cervical cancer cells. Mechanistically, these functions of GLI2 were in part mediated by the activation of AKT pathway. Knockdown of GLI2, but not GLI3, also inhibited xenograft growth of cervical cancer cells in vivo. Finally, analysis of TCGA data showed that high levels of GLI2, but not GLI3, conferred a poor prognosis in cervical cancer patients. These observations for the first time suggest that GLI2, but not GLI3, exerts a tumor-promoting role in cervical cancer and may be targeted as a novel therapeutic strategy.

During aging, besides genetic alterations, genes with altered expression may promote breast cancer development. Using linear regression modeling, we identified 148 up-regulated and 189 down-regulated genes during aging, by analyzing the whole transcriptome profiling data of matched normal tissues from 82 female patients with age and menopausal status available from The Cancer Genome Atlas data. We also compared matched tumor and normal samples, 3356 up-regulated and 3124 down-regulated genes were identified to be affected by tumorigenesis. Overlapping of tumorigenesis-associated genes with age-dependent genes resulted in 14 up-regulated and 24 down-regulated genes with both age and tumorigenesis. These genes were significantly predictive in relapse free survival, indicative of their potential tumor promoting or suppressive functions respectively. To test this hypothesis, we selected two up-regulated genes-DYNLT3 and P4HA3, and two down-regulated genes-ALX4 and WDR86 to investigate their function in controlling breast cancer malignancy because they are novel genes to breast cancer. We found that knockdown of DYNLT3 or P4HA3, and overexpression of ALX4, significantly reduced breast cancer cell proliferation, migration and colony forming capacity in soft agar, while overexpression of WDR86 did not show any inhibitory activity in breast cancer cells. Consistent with the in vitro data, knockdown of DYNLT3, P4HA3 and overexpression of ALX4 inhibited tumor growth and lung metastasis when breast cancer cells were orthotopically implanted in mice, whereas such inhibition was not observed in mice when WDR86-overexpressing breast cancer cells were implanted. Taken together, our results support that some age-related genes harbor tumor promoting or inhibiting functions. Thus, proper modulation of their expression has potential to prevent or slow down the progression of breast cancer. Citation Format: Bingzhi Wang, Xiang Gu, Haiyan Zhu, Luzhe Sun. Novel age-related tumor promoting and inhibiting genes in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 36.