PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study.

BACKGROUND: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. METHODS: We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates. RESULTS: We detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher's exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. CONCLUSIONS: The two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.

Prognostic value of organic anion transporting polypeptide 1B3 and copper transporter 1 expression in endometrial cancer patients treated with paclitaxel and carboplatin.

Paclitaxel and carboplatin (TC) chemotherapy is an effective and well-tolerated regimen against advanced endometrial cancer. Organic anion transporting polypeptide 1B3 (OATP1B3) and copper transporter 1 (CTR1) are critical for the uptake of paclitaxel and carboplatin, respectively. This study aimed to address the prognostic impact of OATP1B3 and CTR1 in endometrial cancer patients treated with adjuvant TC chemotherapy. We immunohistochemically evaluated the expressions of OATP1B3 and CTR1 in 47 stage III endometrial cancers. The high expression levels of OATP1B3 were significantly correlated with type I tumor (P = 0.0005). In univariate analysis, high expression levels of OATP1B3 (P = 0.047) and CTR1 (P = 0.009) were significantly associated with longer disease-free survival (DFS) and longer overall survival (OS), respectively. The patients with tumors showing high expression levels of at least one of OATP1B3 and CTR1 had potentially longer DFS (P = 0.058) and significantly longer OS (P = 0.003) sin the univariate analysis. Combined OATP1B3/CTR1 expression was the sole independent prognostic factor for longer OS in the multivariate analysis (P = 0.013). Our findings suggest that combined OATP1B3/CTR1 expression is a possible predictive/prognostic factor for a good outcome in stage III endometrial cancer patients treated with adjuvant TC chemotherapy.

Endoscopic balloon dilation for obstructive colorectal cancer: a basic study on morphologic and pathologic features associated with perforation.

BACKGROUND: The use of endoscopic dilation and a self-expandable stent for colorectal cancer (CRC) presenting with a stricture or obstruction, either prior to surgery or as a palliative measure (an alternative to colostomy), causes perforation with relative high incidence (1%-17%). OBJECTIVE: To experimentally investigate risk factors associated with perforation in excised CRC specimens. DESIGN: Experimental study. SETTING: Ex vivo experiment on freshly excised human colon cancer specimens at an academic hospital. PATIENTS: This study involved 47 patients with strictured CRCs of <15 mm in internal diameter as assessed by a preoperative contrast enema. INTERVENTION: Immediately after surgical resection, a balloon with a diameter of 18 mm was placed in the stricture. The balloon was inflated slowly with hydrostatic pressure over 1 minute and kept at the maximum diameter for 1 minute. MAIN OUTCOME MEASUREMENTS: Correlations between macroscopic perforation and 20 items, including morphological and histopathological characteristics. RESULTS: Perforation occurred in 8 of 47 (17.0%) CRC specimens. Four items showed statistically significant (P < .05) correlations with perforation: peritumoral proliferation of collagen fibers (relative area > or =23.9% in the visual field), annularity of the tumor, severe stricture (<7.9 mm), and fewer residual smooth muscle cells in the muscularis propria, reflecting tumor encroachment. The best predictor of perforation was a combination of severe stricture and pronounced peritumoral proliferation of collagen fibers. LIMITATIONS: An uncontrolled study with a small number of patients. CONCLUSION: Histopathological and morphological items associated with a decrease in elastic compliance were more important as predictors of perforation than dilation procedure parameters, such as balloon pressure.