Faculty Profiles - KANDA Mitsuro

Papers - KANDA Mitsuro

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Prognostic impact of a microscopic positive margin in patients undergoing gastrectomy for gastric cancer: a propensity score‑matched analysis of a multi‑institutional dataset. Reviewed

Koki Nakanishi, Mitsuro Kanda, Seiji Ito, Yoshinari Mochizuki, Hitoshi Teramoto, Kiyoshi Ishigure, Toshifumi Murai, Takahiro Asada, Akiharu Ishiyama, Hidenobu Matsushita, Dai Shimizu, Chie Tanaka, Michitaka Fujiwara, Kenta Murotani, Yasuhiro Kodera

Surgery today Vol. 52 ( 4 ) page： 559 - 566 2022.4

Language：Japanese Publishing type：Research paper (scientific journal)

PURPOSE: We analyzed the effect of a microscopic positive margin on survival outcomes after gastrectomy for gastric cancer METHODS: We analyzed a multi-institutional dataset to study patients who underwent gastrectomy with curative intent between 2010 and 2014. We used propensity score matching to strictly balance the patients' oncological features, backgrounds, and postoperative treatment to compare the survival outcomes of those with microscopic positive margins and those with negative margins. RESULTS: Among 3029 patients, 32 (1.1%) had positive margins. After matching, we enrolled 128 patients in this retrospective analysis: 32 with a positive margin and 96 with a negative margin. The recurrence-free survival of the positive-margin group was significantly shorter than that of the negative-margin group (hazard ratio [HR], 1.62, 95% confidence interval, 1.00-2.63, p = 0.0485). Consistent results were observed for patients with pStages I-III disease (HR, 1.65, p = 0.0835), whereas the survival curves overlapped in those with pStage IV disease (HR, 1.29, p = 0.5934). The prevalence of overall recurrence in the positive-margin group was higher than that in the negative-margin group (75% vs 58%, p = 0.0917). This trend was consistent with locoregional recurrence (9% vs 3%) and distant recurrence (69% vs 55%). CONCLUSIONS: The survival of patients after curative gastrectomy for gastric cancer was worse in those with microscopic positive margins than in those with negative margins.

DOI： 10.1007/s00595-021-02365-8

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PubMed

食道扁平上皮癌予後マーカーとしてのOPLAH発現 Reviewed

清水大, 神田光郎, 小池聖彦, 佐藤雄亮, 猪川祥邦, 高見秀樹, 服部憲史, 林真路, 田中千恵, 中山吾郎, 本山悟, 藤原道隆, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 122回 page： DP - 5 2022.4

ASO Visual Abstract: SLC7A9 as a Potential Biomarker for Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma. Reviewed International journal

Hayato Baba, Mitsuro Kanda, Koichi Sawaki, Shunsuke Nakamura, Sei Ueda, Dai Shimizu, Masahiko Koike, Yasuhiro Kodera, Tsutomu Fujii

Annals of surgical oncology Vol. 29 ( 4 ) page： 2710 - 2710 2022.4

SLC7A9 as a Potential Biomarker for Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma. Reviewed International journal

Hayato Baba, Mitsuro Kanda, Koichi Sawaki, Shunsuke Nakamura, Sei Ueda, Dai Shimizu, Masahiko Koike, Yasuhiro Kodera, Tsutomu Fujii

Annals of surgical oncology Vol. 29 ( 4 ) page： 2699 - 2709 2022.4

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: The expression of solute carrier (SLC) 7 family genes is reportedly associated with several malignancies. Here, we focused on SLC7A9 and investigated its expression, function, and clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: SLC7A9 transcription levels were evaluated in 13 ESCC cell lines, and polymerase chain reaction (PCR) array analysis was conducted to detect coordinately expressed genes with SLC7A9. SLC7A9 contributions to proliferation, invasion, and migration were evaluated in ESCC cells subjected to siRNA-mediated gene knockdown and pCMV6-entry plasmid-mediated overexpression. SLC7A9 expression was detected in 189 ESCC tissues by quantitative reverse-transcription (qRT)-PCR and correlated with clinicopathological parameters. RESULTS: The expression levels of SLC7A9 varied widely in ESCC cell lines and correlated with FGFBP1 expression. Knockdown of SLC7A9 significantly suppressed the proliferation, invasion, and migration of the ESCC cell lines. Moreover, overexpression of SLC7A9 enhanced cell proliferation and migration. In analyses of clinical specimens, SLC7A9 mRNA was overexpressed in the ESCC tissues compared with the adjacent normal esophageal tissues. High mRNA expression was significantly associated with high levels of squamous cell carcinoma-related antigen and carcinoembryonic antigen, advanced disease stage, and lymph node metastasis. High SLC7A9 expression was also significantly associated with poor disease-specific and disease-free survival, and lymph node recurrence after radical surgery, but not with the other recurrence patterns. On multivariate analysis, high SLC7A9 expression was an independent predictor of lymph node recurrence. CONCLUSIONS: SLC7A9 influences the malignant behavior of ESCC cells. Tumor SLC7A9 expression may serve as a novel biomarker for predicting lymph node metastasis and recurrence in ESCC patients.

DOI： 10.1245/s10434-021-11001-1

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PubMed

Stage II/III胃癌患者における術前Prognostic Nutritional Index値と術後合併症・長期予後との関連 Reviewed

笹原正寛, 神田光郎, 伊藤誠二, 望月能成, 寺本仁, 石榑清, 村井俊文, 浅田崇洋, 石山聡治, 松下英信, 田中千恵, 小林大介, 藤原道隆, 室谷健太, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 122回 page： DP - 1 2022.4

高齢者の上部消化管癌に対する治療方針高齢者機能評価から考える高齢者胃癌に対する治療法 Reviewed

田中千恵, 中西香企, 梅田晋一, 清水大, 猪川祥邦, 高見秀樹, 服部憲史, 神田光郎, 林真路, 中山吾郎, 藤原道隆, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 122回 page： WS - 4 2022.4

治癒切除不能胃癌に対するconversion surgeryの治療実態を調査する多施設共同前向き観察研究 Reviewed

中西香企, 田中千恵, 神田光郎, 清水大, 宮田一志, 藤原道隆, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 122回 page： SF - 1 2022.4

Stage II/III胃癌患者における術前Prognostic Nutritional Index値と術後合併症・長期予後との関連 Reviewed

日本外科学会定期学術集会抄録集 Vol. 122回 page： DP - 1 2022.4

Drain Amylase Concentrations at 3 h After Gastrectomy Enhance Early Prediction of Postoperative Peripancreatic Inflammatory Fluid Collection. Reviewed International journal

Koki Nakanishi, Mitsuro Kanda, Chie Tanaka, Shigeomi Takeda, Katsuhito Tanaka, Dai Shimizu, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera

World journal of surgery Vol. 46 ( 3 ) page： 648 - 655 2022.3

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Despite numerous studies of peripancreatic inflammatory fluid collection (PIFC) that report on the relevance of the drain amylase concentration (D-AMY), early prediction using this assay is problematic. This study aimed to investigate the clinical significance of measuring the D-AMY at 3 h after gastrectomy (POD0) for gastric cancer. METHODS: This retrospective analysis included consecutive patients who underwent gastrectomy combined with peripancreatic lymph node dissection. The predictive value of D-AMY on POD0 and postoperative day 1 (POD1) for clinically relevant PIFC was evaluated together or individually. RESULTS: Analyses were performed in 204 patients. Twenty (9.8%) patients experienced PIFC. D-AMY cutoffs of 721 IU/L on POD0 and 1695 IU/L on POD1 were determined using the receiver operating characteristic curve analysis for predicting PIFC. The D-AMY on POD0 had higher sensitivity (80%) but lower specificity (66.3%) for prediction of PIFC, compared with those of D-AMY on POD1 (65%, 89.1%, respectively). When combination marker analysis was performed, the highest risk group (D-AMY ≥ the cutoff values of POD0 and POD1) were associated with an elevated rate of occurrence (44%) and a high positive likelihood ratio (7.36) compared with those of the single cutoff group. The lowest risk group (D-AMY < the cutoff values on POD0 and POD1) was associated with a low rate of occurrence (2.5%) and low negative likelihood ratio (0.24) compared with those of the single cutoff group. CONCLUSIONS: Combined measurements of D-AMYs on POD0 and POD1 enhanced early prediction of PIFC after gastrectomy.

DOI： 10.1007/s00268-021-06401-z

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PubMed

Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System Reviewed

Yachida Shinichi, Totoki Yasushi, Noe Michael, Nakatani Yoichiro, Horie Masafumi, Kawasaki Kenta, Nakamura Hiromi, Saito-Adachi Mihoko, Suzuki Masami, Takai Erina, Hama Natsuko, Higuchi Ryota, Hirono Seiko, Shiba Satoshi, Kato Mamoru, Furukawa Eisaku, Arai Yasuhito, Rokutan Hirofumi, Hashimoto Taiki, Mitsunaga Shuichi, Kanda Mitsuro, Tanaka Hidenori, Takata So, Shimomura Ayaka, Oshima Minoru, Hackeng Wenzel M., Okumura Tomoyuki, Okano Keiichi, Yamamoto Masakazu, Yamaue Hiroki, Morizane Chigusa, Arihiro Koji, Furukawa Toru, Sato Toshiro, Kiyono Tohru, Brosens Lodewijk A. A., Wood Laura D., Hruban Ralph H., Shibata Tatsuhiro

CANCER DISCOVERY Vol. 12 ( 3 ) page： 692 - 711 2022.3

腹腔鏡下胃切除術における臨床病期Iから病理学的病期II/IIIへと移行した患者の予後(Prognosis of patients with stage migration from cStage I to pStage II/III after laparoscopic surgery) Reviewed

伊藤雄貴, 神田光郎, 伊藤誠二, 望月能成, 寺本仁, 石榑清, 村井俊文, 浅田崇洋, 石山聡治, 松下英信, 田中千恵, 小林大介, 藤原道隆, 室谷健太, 藤田恵三, 三輪高嗣, 田中友理, 間下直樹, 小寺泰弘

日本胃癌学会総会記事 Vol. 94回 page： 439 - 439 2022.3

A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. Reviewed International journal

Jinsei Miyoshi, Zhongxu Zhu, Aiping Luo, Shusuke Toden, Xuantong Zhou, Daisuke Izumi, Mitsuro Kanda, Tetsuji Takayama, Iqbal M Parker, Minjie Wang, Feng Gao, Ali H Zaidi, Hideo Baba, Yasuhiro Kodera, Yongping Cui, Xin Wang, Zhihua Liu, Ajay Goel

Molecular cancer Vol. 21 ( 1 ) page： 44 - 44 2022.2

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis. METHODS: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts. RESULTS: We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79-0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69-0.91]; and n = 165, AUC:0.89 [95%CI:0.83-0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87-0.96]); and (n = 188, AUC:0.93, [95%CI:0.88-0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001). CONCLUSIONS: We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts.

DOI： 10.1186/s12943-022-01507-x

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PubMed

Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer. Reviewed International journal

Souvick Roy, Mitsuro Kanda, Sachiyo Nomura, Zhongxu Zhu, Yuji Toiyama, Akinobu Taketomi, James Goldenring, Hideo Baba, Yasuhiro Kodera, Ajay Goel

Molecular cancer Vol. 21 ( 1 ) page： 42 - 42 2022.2

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC. METHODS: We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies. RESULTS: We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation. CONCLUSIONS: We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.

DOI： 10.1186/s12943-022-01527-7

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PubMed

Optimal preoperative multidisciplinary treatment in borderline resectable pancreatic cancer: Results of a dual-center study Reviewed

Kimura Nana, Yamada Suguru, Takami Hideki, Murotani Kenta, Yoshioka Isaku, Shibuya Kazuto, Sonohara Fuminori, Hoshino Yui, Hirano Katsuhisa, Watanabe Toru, Baba Hayato, Mori Kosuke, Miwa Takeshi, Tanaka Haruyoshi, Kanda Mitsuro, Hayashi Masamichi, Matsui Koshi, Okumura Tomoyuki, Kodera Yasuhiro, Fujii Tsutomu

JOURNAL OF CLINICAL ONCOLOGY Vol. 40 ( 4 ) 2022.2

Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer. Reviewed International journal

Takahiro Inaishi, Masahiro Shibata, Takahiro Ichikawa, Mitsuro Kanda, Masamichi Hayashi, Ikumi Soeda, Dai Takeuchi, Yuko Takano, Nobuyuki Tsunoda, Yasuhiro Kodera, Toyone Kikumori

Oncology reports Vol. 47 ( 1 ) 2022.1

Language：Japanese Publishing type：Research paper (scientific journal)

The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. PFKP is highly expressed in several cancers, and it has been reported to be involved in the progression of cancer cells. However, its oncological role in breast cancer (BC) remains unclear. The present study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC. Firstly, the mRNA and protein expression of PFKP was evaluated in BC and non‑cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to evaluate the correlation between PFKP and 84 cancer‑related genes. Then, PFKP knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness and migration were analyzed. Furthermore, the association between PFKP mRNA expression and clinicopathological factors was investigated in 167 patients with BC. PFKP was highly expressed in estrogen receptor‑negative and human epidermal growth factor receptor 2‑negative BC cell lines. PCR array analysis demonstrated that the expression level of PFKP was significantly correlated with that of transforming growth factor‑β1 and MYC proto‑oncogene. PFKP knockdown significantly decreased the proliferation and invasiveness of MCF7, SK‑BR‑3, and MDA‑MB‑231 cells. Furthermore, cell migration was inhibited in SK‑BR‑3 and MDA‑MB‑231 cells. In the clinical specimens, patients with T2/T3/T4, lymph node metastasis, or stage II/III/IV exhibited higher expression of PFKP mRNA than patients with less severe disease. In conclusion, the present findings indicated that PFKP is involved in promoting tumor‑progressive oncological roles in BC cells across different subtypes and is considered a possible novel therapeutic target for BC.

DOI： 10.3892/or.2021.8220

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Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy. Reviewed International journal

Yuki Sunagawa, Masamichi Hayashi, Suguru Yamada, Hiroshi Tanabe, Keisuke Kurimoto, Nobutake Tanaka, Fuminori Sonohara, Yoshikuni Inokawa, Hideki Takami, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

Clinical epigenetics Vol. 13 ( 1 ) page： 172 - 172 2021.12

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. METHODS: We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017-2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. RESULTS: Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352-9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). CONCLUSION: Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

DOI： 10.1186/s13148-021-01165-8

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Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial. Reviewed International journal

Hironori Ishigami, Yasushi Tsuji, Hisashi Shinohara, Yasuhiro Kodera, Mitsuro Kanda, Hiroshi Yabusaki, Seiji Ito, Motohiro Imano, Hiroharu Yamashita, Akio Hidemura, Hironori Yamaguchi, Takeo Fukagawa, Koji Oba, Joji Kitayama, Yasuyuki Seto

Journal of clinical medicine Vol. 10 ( 23 ) 2021.12

Language：English Publishing type：Research paper (scientific journal)

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

DOI： 10.3390/jcm10235666

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Neoadjuvant docetaxel, oxaliplatin plus S-1 for treating clinical stage III squamous cell carcinoma of the esophagus: Study protocol of an open-label phase II trial. Reviewed International journal

Mitsuro Kanda, Dai Shimizu, Kazushi Miyata, Osamu Maeda, Chie Tanaka, Yoshikuni Inokawa, Norofumi Hattori, Masamichi Hayashi, Masahiko Ando, Yachiyo Kuwatsuka, Kenta Murotani, Goro Nakayama, Masahiko Koike, Yuichi Ando, Tomoki Ebata, Yasuhiro Kodera

Contemporary clinical trials communications Vol. 24 page： 100853 - 100853 2021.12

Language：Japanese Publishing type：Research paper (scientific journal)

In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating resectable stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the requirement for a more effective regimen. We are conducting a single-arm phase II study to assess the safety and efficacy of neoadjuvant docetaxel, oxaliplatin plus S-1 (DOS) for treating patients with clinical stage III ESCC. The primary endpoint is the pathological response rate, and the target number is 45 patients. Safety, response rate, R0 resection rate, and survival are secondary endpoints. This trial is registered in the Japan Registry of Clinical Trials as jRCTs041210023. We are conducting a prospective phase II trial to evaluate the safety and efficacy of three courses of neoadjuvant DOS treatment followed by radical esophagectomy for clinical stage III ESCC.

DOI： 10.1016/j.conctc.2021.100853

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Genomewide Expression Profiling Identifies a Novel miRNA-Based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer. Reviewed International journal

Shimura T, Toden S, Kandimalla R, Toiyama Y, Okugawa Y, Kanda M, Baba H, Kodera Y, Kusunoki M, Goel A

Annals of surgery Vol. 274 ( 5 ) page： E425 - E434 2021.11

Language：Japanese Publishing type：Research paper (scientific journal)

OBJECTIVE: This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA: Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS: We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS: Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS: We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

DOI： 10.1097/SLA.0000000000003647

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Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer. Reviewed International journal

Takahiro Ichikawa, Masahiro Shibata, Takahiro Inaishi, Ikumi Soeda, Mitsuro Kanda, Masamichi Hayashi, Yuko Takano, Dai Takeuchi, Nobuyuki Tsunoda, Yasuhiro Kodera, Toyone Kikumori

Current oncology (Toronto, Ont.) Vol. 28 ( 5 ) page： 4080 - 4092 2021.10

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. METHODS: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients' clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. RESULTS: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. CONCLUSION: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.

DOI： 10.3390/curroncol28050346

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PubMed

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