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Introduction: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. Methods: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. Results: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). Conclusion: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

Given the increased incidence of esophageal cancer (EC) in individuals over 80 years old, the optimum therapeutic strategy for elderly patients is needed to be established with scientific evidence. Here, we studied the short-term and long-term outcomes after treatment of patients aged 80 years old or older with EC.Eighty patients with EC aged 80 years old or older, who underwent esophagectomy (n=23), definitive chemoradiotherapy (dCRT) (n=46) or best supportive care (n=11) between January 2010 and March 2019 were included in this study, and clinical data were compared among these groups.Surgery had a great benefit on the 3-year overall survival (OS) compared to dCRT (68.4% vs. 29.3%, p0.01). The cure rates of treatment were 86.9% in surgery and 34.8% in dCRT. dCRT led to a better 3-year OS compared to BSC (29.3% vs. 0%, p0.01); however, dCRT did not improved OS in patients with T4. Patients with T4 had high frequency of adverse events and treatment-related death in dCRT; CTCAE Grade 3-5 was observed in 100% of all T4 patients and Grade 5 in 57.1%. Multivariate analysis revealed that T4 was an independent risk factor of treatment-related death after dCRT (p0.01).Surgery is the first treatment option for resectable EC even in elderly patients, and dCRT can be considered as an alternative. However, dCRT may induce severe toxicity especially in T4 EC patients.

Background/Aim: The immune system has a pivotal role in modulating the response to chemotherapy in breast cancer (BC). However, the immune status during chemotherapy remains unclear. We evaluated the sequential changes in peripheral systemic immunity markers in BC patients treated with various chemotherapeutic agents. Materials and Methods: We examined the correlation between the peripheral systemic immunity markers, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC) and the local cytolytic activity (CYT) score obtained by quantitative reverse-transcription polymerase chain reaction of 84 preoperative BC patients. Next, we observed the sequential changes in the peripheral systemic immunity markers during treatment with four anticancer drugs: oral 5-fluorouracil derivative; S-1, epirubicin plus cyclophosphamide; paclitaxel plus the anti-vascular endothelial growth factor antibody bevacizumab, and eribulin in 172 HER2-negative advanced BC patients. Finally, we examined the correlation between the changes in the peripheral systemic immunity markers, time to treatment failure (TTF) and progression-free survival (PFS). Results: A negative correlation was found between ALC and NLR. ALC-low and NLR-high cases were positively associated with CYT score-low cases. The ratio of ALC-increase and NLR-decrease varies depending on the anticancer drugs used. The responder group (TTF ≥3 months) had a higher NLR-decrease ratio than the nonresponder group (TTF

To further improve the prognosis of locally advanced esophageal cancer patients, investigating new perioperative treatment strategies is necessary. The current study aimed to retrospectively investigate neoadjuvant radiotherapy with cisplatin and 5-fluorouracil (CF-RT) and radiotherapy with docetaxel and CF (DCF-RT) and compare their treatment outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC).We retrospectively reviewed 95 patients with ESCC who received CF-RT or DCF-RT followed by esophagectomy. The CF-RT group received chemotherapy consisting of two courses of CF repeated every 4 weeks. The DCF-RT group received chemotherapy consisting of two courses of DCF repeated every 2 weeks. A radiotherapy dose of 1.8-2 Gy was administered per session, up to a total of 40-41.4 Gy. Adverse events of neoadjuvant chemoradiotherapy, surgical outcomes, pathological responses, prognosis, and recurrence patterns were evaluated.Both the CF-RT and DCF-RT groups had equivalent pathological complete response rates of the primary tumor at 31.6% and 38.6%, respectively. However, the DCF-RT group had significantly better 5-year disease-free survival and 5-year overall survival than (HR=0.50, 95%CI=0.26-0.97, p=0.0392) than the CF-RT group.DCF-RT may be a candidate neoadjuvant therapy for locally advanced ESCC.

Cancer is a leading cause of death worldwide, and the incidence continues to increase. Despite major research aimed at discovering and developing novel and effective anticancer drugs, oncology drug development is a lengthy and costly process, with high attrition rates. Drug repositioning (DR, also referred to as drug repurposing), the process of finding new uses for approved noncancer drugs, has been gaining popularity in the past decade. DR has become a powerful alternative strategy for discovering and developing novel anticancer drug candidates from the existing approved drug space. Indeed, the availability of several large established libraries of clinical drugs and rapid advances in disease biology, genomics/transcriptomics/proteomics and bioinformatics has accelerated the pace of activity‐based, literature‐based and in silico DR, thereby improving safety and reducing costs. However, DR still faces financial obstacles in clinical trials, which could limit its practical use in the clinic. Here, we provide a brief review of DR in cancer and discuss difficulties in the development of DR for clinical use. Furthermore, we introduce some promising DR candidates for anticancer therapy in Japan., We provide a brief review of drug repositioning (DR) in cancer and discuss difficulties in the development of DR for clinical use. Furthermore, we introduce some promising DR candidates for anticancer therapy in Japan.

Background/aim Kinesin family member 15 (KIF15) participates in the transport of macromolecules in essential cellular processes. In this study we evaluated the clinical relevance of KIF15 expression in hepatocellular carcinoma (HCC). Materials and methods Association between KIF15 expression and clinical outcomes in HCC patients was analyzed using three independent cohorts. Localization of KIF15 expression was assessed by immunohistochemical analysis. Co-culture experiments were performed using healthy donor peripheral blood mononuclear cells (PBMC) and HCC cell lines. Results Immunohistochemical analysis showed that KIF15 was mainly expressed in inflammatory monocytes around cancer cells. Multivariate analysis indicated high KIF15 expression was an independent poor prognostic factor for survival. HCC cells with high expression of minichromosome maintenance protein 2 (MCM2) were located close to KIF15-expressing inflammatory monocytes. The proliferation ability of HCC cells was increased by co-culture with PBMC. Conclusion High KIF15 expression in inflammatory monocytes in tumor tissues may serve as a prognostic marker for poor outcome in HCC.

Background/Aim: To investigate changes in post-progression chemotherapy (PPC) before and after nivolumab approval and determine their prognostic impact. Patients and Methods: A total of 146 patients with unresectable gastric cancer who had at least progressive disease after first- and/or second-line chemotherapy were retrospectively enrolled. Results: Among the 146 patients, 46 and 23 received ramucirumab and nivolumab, respectively. Moreover, 95 and 62 patients received PPC after first- and second-line chemotherapy, respectively. Group B (i.e., at least chemotherapy after nivolumab approval) had significantly higher proportions of patients receiving ramucirumab therapy, nivolumab therapy, and PPC after first- or second-line chemotherapy compared to group A (i.e., termination of chemotherapy before nivolumab approval). Group A had significantly poorer prognosis than group B. Multivariate analysis showed that age, number of distant metastatic sites, and ramucirumab therapy were independent prognostic factors. Conclusion: Changes in chemotherapeutic strategies, including PPC, might contribute to improved prognosis in patients with advanced gastric cancer.

Alternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1.

Background/aim The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy. Patients and methods We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS. Results The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients. Conclusion Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS.

Background/aim To determine the prognostic utility of trastuzumab-based chemotherapy based on human epidermal growth factor receptor 2 (HER2) expression in patients with para-aortic lymph node (PAN) metastasis from gastric cancer. Patients and methods A total of 41 patients with clinical PAN metastasis from gastric cancer who underwent chemotherapy were retrospectively enrolled. Results Eighteen (43.9%) patients had HER2-positive tumors and consequently, received trastuzumab-based chemotherapy. A total of 11 patients underwent surgery. HER2 status was significantly correlated with the number of distant metastatic sites, the presence or absence of trastuzumab-based chemotherapy, and the presence or absence of gastrectomy. HER2-positive patients had significantly better prognosis than HER2-negative patients. Multivariate analysis identified age and trastuzumab-based chemotherapy based on HER2 status as an independent prognostic factor. Conclusion Assessing HER2 expression and subsequent trastuzumab-based chemotherapy can be an effective method for determining the prognosis of patients with PAN metastasis from gastric cancer.

Background: The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC. Methods: Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery. Results: The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006). Conclusion: The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.

BackgroundPeritoneal dissemination (PD) frequently occurs in gastric cancer (GC) and is incurable. In this study, we aimed to identify novel PD-associated genes and clarify their clinical and biological significance in GC.Materials and methodsWe identified LOXL1 as a PD-associated candidate gene by in silico analysis of GC datasets (highly disseminated peritoneal GC cell line and two freely available GC datasets, GSE15459 and TCGA). Next, we evaluated the clinical significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a validation cohort (Kyushu cohort). Moreover, we performed gene expression analysis, including gene set enrichment analysis (GSEA) with GSE15459 and TCGA datasets. Finally, we performed a series of in vitro experiments using GC cells.ResultsIn silico analysis showed that LOXL1 was overexpressed in tumor tissues of GC patients with PD and in highly disseminated peritoneal GC cells, relative to that in the control GC patients and cells, respectively. High expression of LOXL1 was a poor prognostic factor in the TCGA dataset. Next, IHC showed that LOXL1 was highly expressed in GC cells. High LOXL1 mRNA expression was associated with poorly differentiated histological type, lymph node metastasis, and was an independent poor prognostic factor in the Kyushu validation cohort. Moreover, LOXL1 expression was positively correlated with the EMT (epithelial-mesenchymal transition) gene set in GSEA. Finally, LOXL1-overexpressing GC cells changed their morphology to a spindle-like form. LOXL1 overexpression reduced CDH1 expression; increased the expression of VIM, CDH2, SNAI2, and PLS3; and promoted the migration capacity of GC cells.ConclusionsLOXL1 is associated with PD in GC, possibly through the induction of EMT.

BACKGROUND/AIM Certain chromosomal arms are clonally amplified in colorectal cancer (CRC) and may contain novel driver genes. The aim of this study was to identify a novel driver gene for colorectal cancer carcinogenesis on long arm of chromosome 7 and the clarify its biological function. MATERIALS AND METHODS We identified ArfGAP with GTPase domain, ankyrin repeat and PH domain 3 (AGAP3) as a putative driver gene using the CRC dataset in The Cancer Genome Atlas (TCGA). Biological functions of AGAP3 and CRMP5-associated GTPase (CRAG), a splicing variant of AGAP3, were explored by overexpression. AGAP3/CRAG expression in our cohort was examined by quantitative reverse transcription polymerase chain reaction. Clinical significance of AGAP3/CRAG expression in TCGA dataset, Gene Expression Omnibus datasets and our clinical cohort was evaluated. RESULTS AGAP3 expression was significantly increased in CRC and colorectal adenoma compared to normal tissue. CRAG overexpression up-regulated c-Jun expression, and significantly increased cell proliferation and colony formation capability. AGAP3 expression did not have a concordant association with patient prognosis among datasets. CONCLUSION CRAG may contribute to development of CRC via activator protein 1 activation.

Background/aim Circulating microRNAs (miRs) in blood have been highlighted as diagnostic, prognostic and predictive biomarkers for "Precision medicine". This study aimed to explore the possibility of using circulating precursor miRs (pre-miRs) as clinical biomarkers of recurrence in breast cancer. Materials and methods We performed miR microarray analyses of circulating miRs in blood from patients with or without recurrence of breast cancer and identified miR-488-5p as a recurrence-related miR. Then, the expression levels of pre-miR-488 or miR-488-5p were measured by RT-qPCR and the clinicopathological and prognostic significance of circulating pre-miR-488 was assessed in the blood of breast cancer patients. Results A positive correlation was noted between pre-miR-488 and miR-488-5p expression in blood. In 330 cases of surgically-treated breast cancer, high expression of circulating pre-miR-488 was an independent poor prognostic factor for recurrence-free survival. Conclusion Circulating pre-miR-488 expression could be a novel prognostic biomarker for predicting recurrence in breast cancer patients.

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC., Author summary We found that copy number aberrations (CNAs) may be the most important selective pressure promoting cancer evolution from early-to-advanced tumors in primary sites. The diminished neoantigens (NAG) in cancer cells and the diverse TCR repertoire in cytotoxic T cells were crucial for the onset of postoperative recurrence during genomic neutral evolution, along with clonal CNA and several driver SNVs from primary to recurrent sites. Therefore, cancer metastasis could be prevented by activating CTL at the premetastatic sites before priming of the metastatic process.

Background: Pancreatic cancer (PC) is the most lethal cancer in humans, with a 5-year survival rate of less than 10%. Thus, identification of prognostic biomarkers as well as molecular therapeutic targets should be critical. Translational reprogramming in cancer has been attracting attention. Several studies have reported that genomic alternations of a translational regulatory gene contributing to malignancy. eIF5-mimic protein 1 (5MP1), previously termed BZW2 is a member of the bZIP superfamily of transcription factors. 5MP1 is reported to be upregulated and has a pro-tumor effect via activation of the Akt/mTOR signaling pathway in osteosarcoma. However, the role and mechanisms of 5MP1 in PC remains unknown. The aim of this study is to clarify the clinical significance of 5MP1 expression in PC. Material and method: Firstly, we analyzed public datasets of PC (178 RNA-sequencing data from The Cancer Genome Atlas, 36 gene expression array data from GSE 15471, 45 gene expression array data from GSE 28735, 69 gene expression array data from GSE 62452, 145 primary PC and 46 normal pancreas gene expression array data from GSE 71729, 45 Copy number variation and expression array data from Broad-Novartis Cancer Cell Line Encyclopedia(CCLE)). Then we performed Gene set enrichment analysis (GSEA) to identify the gene sets which were associated with the expression of 5MP1 in PC. Finally, we investigated the localization of 5MP1 by immunohistochemical staining data of THE HUMAN PROTEIN ATLAS and also confirmed with staining our histological specimens. Results: In tumor tissues, mRNA expression of 5MP1 was higher than normal tissues (t-test. p Conclusion and Significance: We demonstrated that 5MP1 was overexpressed in PC cells, and the high expression was associated with poor prognosis. These results suggest that 5MP1 may be associated with tumor progression and can be a promising biomarker for a patient with a poor prognosis of PC. Now we are performing a knockdown experiment for 5MP1 to clarify its biological significance in PC. Citation Format: Yushi Motomura, Takaaki Masuda, Kuniaki Sato, Atsushi Fujii, Akihiro Kitagawa, Hiroaki Wakiyama, Kensuke Koike, Junichi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Katsumi Sakamoto, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori. Clinical significance of eif5-mimic protein 1 in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 475.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and the second leading cause of cancer-related deaths in developed countries, with the majority of deaths being attributed to distant metastasis. Therefore, it is necessary to identify a novel biomarker for cancer progression and metastasis, one that could also be a useful therapeutic target in CRC. Amplification of chromosome 7p is frequent in CRC, and it has been considered to harbor driver genes that promote tumorigenesis or tumor progression by the gain of function. We aimed to identify novel candidate driver genes on chromosome 7p and to clarify the clinical significance of their expression in CRC. Material and Methods: 1. We selected the candidate genes that satisfied the following criteria using CRC data from The Cancer Genome Atlas (TCGA). 1) The DNA copy number and mRNA expression are positively correlated with each other, 2) overexpressed in the tumor tissues compared to the normal tissues. 2. The mRNA expression of the candidate genes was measured in 147 surgically-resected CRC tissues and the paired normal tissues in our hospital by quantitative RT-PCR. The differences of mRNA expression between CRC tissues and normal tissues were analyzed by Mann Whitney U-test. 3. Survival analysis between high and low expression group of the candidate genes was performed by the Kaplan-Meier method. Correlation between the mRNA expression of the candidate genes and the clinicopathological factors were analyzed by Fisher’s exact test. 4. Gene Set Enrichment Analysis (GSEA) was performed in CRC data from TCGA to clarify the correlation between the candidate genes and gene sets that are associated with tumorigenesis or tumor progression. Results: The Golgi to ER traffic protein 4 (GET4) was identified as a candidate driver gene. GET4 is known to be one factor of the BCL2-associated athanogene 6 (BAG6) chaperone complex and function as a regulator for the nucleo-cytoplasmic transport of BAG6. The BAG6 complex is implicated in diverse cellular processes including apoptosis, co-chaperone, and DNA damage response. The expression of GET4 was significantly higher in CRC tissues than in normal colon tissues (p=0.03), and it correlated with depth invasion (p=0.02), and lymphatic invasion (p=0.01). The high GET4 expression group had a significantly poorer prognosis than the low expression group (p=0.02). On multivariate analysis, distant metastasis was an independent prognostic factor affecting OS (p Conclusions: GET4 could be a promising driver gene of CRC on chromosome 7p possibly through regulating the location of BAG6. GET4 may be a therapeutic target as well as a poor prognostic biomarker in CRC. Note: This abstract was not presented at the meeting. Citation Format: Kensuke Koike, Takaaki Masuda, Kuniaki Sato, Yuushi Motomura, Jyunnichi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Atsushi Fujii, Akihiro Kitagawa, Miwa Noda, Yusuke tsuruda, Hajime Ootu, Yousuke Kuroda, Hidetoshi Eguchi, Takashi Nakagawa, Koushi Mimori. Clinical significance of GET4 expression in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5238.

Background : Hepatocellular carcinoma (HCC) is one of the most threatening malignancies because of the limited availability of radical therapeutic options. Thus, identification of prognostic biomarkers as well as molecular therapeutic targets of HCC should be very important for HCC patients. Fanconi anemia complementation group E (FANCE) is a DNA repair-related gene and it’s deletion is one of causes of Fanconi anemia. Recent studies reported that FANCD2 which is activated by FA complex involving FANCE shows high expression in HCC and expression of FANCD2 is in direct proportion to the grade of malignancy of HCC (Anticancer Res, 2017). And other studies reported that FANCE shows high expression in breast cancer (J Mol Biol, 2015). However clinical significance of FANCE expression in HCC is unknown. Objective : To clarify the clinical significance of FANCE expression in HCC. Material and method: Firstly, we assessed the relation between mRNA expression of FANCE and prognosis using large scale HCC gene data sets (The Cancer Genome Atlas; TCGA, Gene Expression Omnibus; GEO, and European Genome-phenome Archive; EGA). Secondly, the mRNA expression of FANCE was measured in 72 surgically resected HCC in our hospital during the period from 2000 to 2004 by RT-qPCR (normalized by internal control GAPDH), and we compared the expression of FANCE in between tumors and normal tissues. Thirdly, we assessed the associations between expression of FANCE and clinicopathological factors. Finally, we investigated the localization of FANCE by immunohistochemical staining data of THE HUMAN PROTEIN ATLAS. Result: In large scale HCC gene data sets and our samples, tumor tissues have higher mRNA expression of FANCE than normal tissues(t test. p Discussion: FANCE was overexpressed in HCC cells, and the high expression of FANCE was associated with poor prognosis. So high expression of FANCE could be a prognostic biomarker in HCC. Now we are performing knockdown experiment for FANCE to clarify the biological significance of FANCE expression in HCC.Conclusion: FANCE could be a prognostic biomarker in HCC. Citation Format: Junichi Takahashi, Takaaki Masuda, Yosuke Kuroda, Akihiro Kitagawa, Yushi Motomura, Kensuke Koike, Dai Shimizu, Shotaro Kuramitsu, Atsushi Fujii, Miwa Noda, Kuniaki Sato, Yusuke Tsuruda, Hajime Otsu, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Koshi Mimori. Clinical significance of Fanconi anemia complementation group E(FANCE)DNA repair-related gene expression in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3173.

Introduction: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with extremely poor overall survival. There is no available molecular marker in clinical application until now. SATB1(special AT-rich binding protein 1) tether genomic DNA in nucleolus and hold three-dimensional structure of genomic DNA. We evaluated SATB1 expression using clinical samples from patients of ESCC and analyzed the association with clinicopathological factors and prognosis to identify novel prognostic marker in ESCC. In addition, we investigated the function of SATB1 using ESCC cells. We focused on matrix metalloproteinase protein (MMP3), which has a SATB1 binding site in its upstream. Materials and Methods: We accumulated 71 samples of ESCC patients who underwent primary tumor resection. The relative expression levels of SATB1 were obtained by normalizing the amount of SATB1 mRNA with respect to GAPDH mRNA as an endogenous control for each sample. We divided 71 ESCC samples into 2 groups, which are SATB1 low expression group (n=35) and SATB1 high expression group (n=36) according to the median of SATB1 expression level, and performed the comparison between two groups. In order to elucidate biological significance, we generated SATB1 overexpression stable transfectants in KYSE150, and performed migration and invasion assays. Next, we knockdowned SATB1 expression of KYSE410, which are ESCC lines, using SATB1 siRNA and evaluated the capability of migration and invasion. Moreover, to validate whether SATB1 altered MMP3 genomic locus, we analyzed comparative genomic hybridization (CGH) array obtained from 54 esophageal cancer samples. We examined MMP3 expression in SATB1 overexpression cells using qRT-PCR. Result: The SATB1 high expression group showed greater tumor depth than the low expression group (P=0.003). In the overall survival curve, patients in the SATB1 high expression group had a significant poorer prognosis than those in the SATB1 low expression group (P=0.013). Multivariate analysis showed that the level of SATB1 expression was an independent prognostic predictor (OR; 1.56, 95%CI; 1.04 - 2.44, P = 0.043). SATB1 transfectants significantly increased the capability of migration and invasion compared to mock (P Conclusion: We indicated that SATB1 is novel prognostic factor in ESCC and that SATB1 promote migration and invasion of ESCC cells. SATB1 may be a promising new candidate for targeted therapies for ESCC. Citation Format: Yusuke Tsuruda, Ryunosuke Kogo, Shuhei Ito, Akihiro Kitagawa, Atsushi Fujii, Shotaro Kuramitsu, Dai Simizu, Yosuke Kuroda, Hidetoshi Eguchi, Tkaaki Masuda, Shoji Natsugoe, Masaki Mori, Koshi Mimori. SATB1 is a novel prognostic factor in esophageal cancer patients and promotes migration and invasion of esophageal cancer cells [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 1552.