Oncoplastic breast surgery combining partial mastectomy with resection of double equilateral triangular skin flaps.

The treatment of early breast cancer using oncoplastic breast surgery (OBS) has been gradually increasing in popularity and is recognized for its efficacy in local control and excellent cosmetic results. We herein report a useful technique for obtaining symmetry of the breast shape for an early breast lesion located in an outer area, close to the nipple-areola, in a Japanese patient with ptotic, fatty breasts. We designed two equilateral triangles: one just upon the resected area and the other on the axilla. They were located on a straight line, with one top pointed to the cranial side and one to the caudal side. A crescent area around the areola was de-epithelialized in the 12 o'clock and 6 o'clock directions. Columnar-shaped breast tissue and an equilateral triangular skin flap and fatty tissue were removed together. To fill the defect, a skin-glandular flap was slid horizontally after suturing the inframammary line. Although an incision scar was formed on the breast and lateral chest wall in a Z-shape, this new technique was able to achieve not only cancer control but also excellent cosmetic results.

Molecular pathogenesis of breast cancer: impact of miR-99a-5p and miR-99a-3p regulation on oncogenic genes.

Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.

The usefulness and utilization of a detachable steel wire-rimmed retractor (KN retractor) for endoscopic thyroid and parathyroid surgery.

PURPOSE: In endoscopic surgery, surgeons occasionally encounter difficulties due to visual field obstruction by muscles or blood vessels. In these situations, specialized instruments that can effectively retract these obstructions are required. Recently, we developed a new detachable wire-rimmed retractor (KN retractor) for narrow-space surgery. METHODS: We evaluated the utility of this KN retractor in 15 patients with thyroid and parathyroid disease. Of those, five patients with papillary thyroid cancer had gasless endoscopic hemithyroidectomy with central node dissection, five underwent endoscopic total thyroidectomy for Graves' disease, and the remaining five received endoscopic parathyroidectomy with gas insufflation. RESULTS: Surgeons were able to perform meticulous operations in a satisfactory visual field supported by the KN retractor. In all patients, the strap muscles were preserved without cutting. The average operating time was 149, 154, and 81 min in patients who underwent hemithyroidectomy with central node dissection, total thyroidectomy, and parathyroidectomy, respectively. Gas insufflation was successfully completed in all cases while maintaining sufficient airtightness. CONCLUSIONS: The KN retractor is suitable for both the gasless lifting method and gas insufflation surgery in a narrow space. We believe that the KN retractor is a new device that will greatly improve the safety and shorten the operation time in endoscopic surgery.

Lung recurrence and its therapeutic strategy in patients with pancreatic cancer.

BACKGROUND: /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion. METHODS: We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A. RESULTS: The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUVmax of the primary pancreatic tumor. CONCLUSIONS: Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUVmax of the primary pancreatic tumor.

Correction: Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

[This corrects the article DOI: 10.1371/journal.pgen.1005778.].

Oncoplastic breast surgery combining partial mastectomy with a triangular skin resection and re-centralization of the nipple-areola.

The treatment of early breast cancer using breast conservation therapy (BCT) commonly ensures local control and acceptable cosmetic results. We herein report a useful technique to obtain symmetry of the breast shape and a level inframammary line and nipple-areola, which achieved excellent results. Six Japanese patients with early breast cancer located on the upper area of the breast were enrolled into this study. A triangle-shaped area of skin was removed together with cancerous and healthy-surrounding breast tissue. Two crescents were designed and de-epithelialized in the directions of 9 o'clock and 3 o'clock. The width of the crescent was decided to be the same as a half or the length of the base of a triangle to be removed. After partial mastectomy, the inner and outer glandular flaps were horizontally sutured. The operations were simple to perform and were not associated with any postoperative complications. Oncoplastic breast surgery combining partial mastectomy with triangular skin resection and re-centralization of the nipple-areola was useful for patients with breast cancer on the upper quadrant area of non-ptotic breasts.

Upgraded bidirectional approach video-assisted neck surgery (BAVANS) using a rigid endoscope with variable viewing direction for advanced endoscopic lymph node dissection in thyroid cancer patients.

In 2011, we developed bidirectional approach video-assisted neck surgery (BAVANS) for endoscopic thyroid cancer surgery. BAVANS combines two different approach pathways at 180 degrees to the cervical lesion for endoscopic thyroidectomy and complete cervical lymphadenectomy. We reported previously that the cranio-caudal approach is extremely useful for endoscopic complete lymph node dissection around the trachea. In 2014, we upgraded the initial BAVANS for better maneuverability and quality of lymph node dissection. A new high-tech rigid endoscope with a variable viewing direction (EndoCAMeleon™), has enabled us to reduce the camera port in the anterior neck while keeping the easy maneuverability and the same quality of central lymph node dissection (LND) as with the initial BAVANS. Endoscopic thyroid cancer surgery is now evolving concurrently with new visual technology.

Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3.

Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.

Intraoperative Identification of the Parathyroid Gland with a Fluorescence Detection System.

BACKGROUND: Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents. METHODS: Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed. RESULTS: The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands. CONCLUSION: The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.

8q24 Polymorphisms and Diabetes Mellitus Regulate Apolipoprotein A-IV in Colorectal Carcinogenesis.

BACKGROUND: Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity. METHODS: 8q24 rs6983267 polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed. RESULTS: Of genes associated with a minor SNP allele at 8q24, diabetes, and MYC overexpression, apolipoprotein A-IV (ApoA-IV) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high ApoA-IV expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV-related oncogenesis in diabetic patients. CONCLUSIONS: Changes in lipid metabolism associated with aberrant expression of ApoA-IV were risks for CRC oncogenesis.

Therapeutic mammoplasty combining partial mastectomy with nipple-areola grafting for patients with early breast cancer: a case series.

PURPOSE: Therapeutic mammoplasty (TM) for breast cancer is a widely practiced oncoplastic technique. Intraductal spread towards the nipple or the location of the cancerous lesion on the central breast may become a contraindication for breast-conserving surgery. We herein report the results of TM in such cases. METHODS: Six patients underwent TM that combined partial mastectomy with free nipple-areola (NA) grafting. The nipple was removed together with the cancerous lesions, and the areola was preserved for NA reconstruction. The tumors were located in the lower quadrant (n = 1), the central area (n = 1), the upper-outer area (n = 2), and the upper-inner area (n = 2). The types of mammoplasty that were performed included: amputation (n = 1), inverted T mammoplasty (n = 3), and L mammoplasty (n = 2). With the exception of one patient, all patients underwent inverted T mammoplasty on the contralateral breast in order to achieve symmetry. RESULTS: The total surgical and plastic periods ranged from 155 to 235 min (mean 207 min) and 100 to 150 min (mean 121 min), respectively. Oncological safety and excellent cosmetic results were achieved. CONCLUSIONS: TM combining partial mastectomy with NA grafting was successfully performed in patients with early-stage cancer in all quadrant areas.

[ONCOPLASTIC BREAST SURGERY AND BREAST RECONSTRUCTION].

Surgical treatment offering both cure and good cosmetic outcomes is important in patients with breast cancer. Mastectomy followed by breast reconstruction is performed with a combination of autologous tissue or implant and can be immediate or delayed in one stage or two stages, respectively. Breast surgeons and plastic surgeons should understand the characteristic indications for surgery and select the appropriate procedure for each patient. Oncoplastic breast surgery (OBS) at the time of breast-conserving surgery is classified into two main methods, volume replacement and volume displacement. It is necessary for clinicians to understand both the advantages and disadvantages of oncoplastic procedures. The problem of some OBS methods remaining ineligible for coverage by national health insurance in Japan remains unresolved, but OBS will become more important as a novel method offering a balance between cancer curability and excellent cosmetic results in the near future.

Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). METHODS: The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. RESULTS: Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. CONCLUSIONS: Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

A Long Non-coding RNA Activated by Transforming Growth Factor-ß is an Independent Prognostic Marker of Gastric Cancer.

BACKGROUND: A recent study reported that long non-coding RNA activated by TGF-ß (lncRNA-ATB) induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-ß (TGF-ß)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients. MATERIALS AND METHODS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-ß, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-ß1 or TGF-ß receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. RESULTS: The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73-7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-ß in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression. CONCLUSION: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-ß/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.

Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer.

BACKGROUND: RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC). METHODS: The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples. RESULTS: TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p < 0.05), and tended to have more frequent venous invasion than the low-TTF1 expression group. Furthermore, the high-TTF1 expression group had a significantly poorer prognosis than the low-TTF1 expression group (p = 0.011). Moreover, overexpression of TTF1 enhanced the proliferation and migration capacity of CRC cells in vitro. GSEA revealed that TTF1 was significantly associated with the RAS and MYC pathways, and this observation was confirmed in samples from 136 patients with CRC. CONCLUSION: TTF1 was involved in cancer progression via the RAS and MYC pathways in CRC, suggesting that TTF1 may be a prognostic indicator and therapeutic target in CRC.

The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer.

BACKGROUND: MicroRNAs have roles in the regulation of the epithelial-mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer. METHODS: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3' untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines. RESULTS: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P < 0.05). Low miR-506 expression was significantly correlated with high SNAI2 expression (P = 0.009) and poorly differentiated type (P = 0.015). In vitro, miR-506 suppressed SNAI2 expression by binding to its 3'UTR, resulting in increased expression of E-cadherin (P < 0.05), verified by immunohistochemical analysis. Pre-miR-506 transfected cells showed significantly suppressed cell proliferation and migration (P < 0.05) compared with the control cells. CONCLUSIONS: The EMT was directly suppressed by miR-506, and its low expression was an independent prognostic factor in gastric cancer patients. The data indicated that miR-506 may act as a tumor suppressor and could be a novel therapeutic agent.

Impaired wound healing and expansion of a large ulcer after bevacizumab with paclitaxel for skin metastases from breast cancer: report of a case.

A 48-year-old Japanese woman was found to have local recurrence of breast cancer in the chest wall following neoadjuvant chemotherapy, total mastectomy with axillary lymphadenectomy, postoperative radiation therapy to the chest wall, and adjuvant systemic therapy using trastuzumab. As a third line of treatment after recurrence, bevacizumab with paclitaxel was initiated for several metastatic lesions on the skin of the chest wall, left internal costal lymph nodes, and right axillary lymph nodes. The wound on the chest wall continued to expand in diameter and depth after the third course of bevacizumab with paclitaxel until the rib was exposed. After stopping the bevacizumab, granulation tissue expanded and by 3 months, had covered the bottom of the ulcer. The patient died soon thereafter, despite systemic chemotherapy with eribulin; however, there was no further bleeding from the ulcer on the chest wall or the exposed ribs.

Aberrant expression of plastin-3 via copy number gain induces the epithelial-mesenchymal transition in circulating colorectal cancer cells.

PURPOSE: Plastin-3 (PLS3) is a novel marker for circulating tumor cells (CTCs) in colorectal cancer (CRC). We sought to investigate the mechanisms mediating the aberrant expression of PLS3, the role of PLS3 in the epithelial-mesenchymal transition (EMT), and its association with the acquisition of invasive and metastatic abilities in human CRC. METHODS: The expression levels of PLS3 messenger RNA in the tumor drainage venous blood (TDB) were examined in 177 CRC cases, and the associations between PLS3 expression and Xq23 copy numbers were analyzed in 132 CRC samples. We then established a stable PLS3-expressing CRC cell line and assessed the role of PLS3 in the EMT. RESULTS: In clinical CRC cases, high expression of PLS3 in CTCs of TDB as well as peripheral blood was established as an independent prognostic factor of overall survival (p < 0.001), and the copy number gain of Xq23, which is the locus of the PLS3 gene, was significantly related to PLS3 overexpression. PLS3 induced the EMT via transforming growth factor (TGF)-ß signaling and resulted in the acquisition of invasive ability in CRC cells. CONCLUSIONS: The aberrant expression of PLS3 was associated with copy number gain in CTCs from primary tumors and was involved in the regulation of the EMT, contributing to a poor prognosis in CRC patients.

Clinical significance of GAB2, a scaffolding/docking protein acting downstream of EGFR in human colorectal cancer.

PURPOSE: Recent studies indicated that the scaffolding adaptor protein GAB2 (GRB2-associated binding protein 2) plays a critical role in the proliferation and migration of various cancers. This study aimed to determine the role of aberrant GAB2 expression in human colorectal cancer (CRC). METHODS: Quantitative real-time reverse transcription polymerase chain reaction was used to evaluate GAB2 mRNA expression in 152 CRC tissues samples to determine the clinicopathological significance of GAB2 expression. We also performed in vitro proliferation assays using siGAB2-transfected CRC cells. RESULTS: GAB2 expression in tumor colorectal tissues was significantly higher than in normal colorectal tissues (p = 0.0212). High GAB2 expression levels were associated with malignant clinicopathologic potential factors, including lymphatic invasion (p = 0.0003), venous invasion (p = 0.0170), and liver metastasis (p = 0.0144). The survival rate of patients with high GAB2 expression levels was significantly lower than that of patients with low GAB2 expression (p = 0.0074). Multivariate analysis indicated that GAB2 expression was a factor affecting lymph node metastasis. Cell proliferation was significantly suppressed by siGAB2 expression in CRC cells in vitro. CONCLUSIONS: GAB2 expression was associated with lymph node metastasis and may play a role in the growth and metastasis of CRC. These results suggest that GAB2 is a potential therapeutic target in CRC.