BACKGROUND Stool DNA (sDNA) methylation analysis is a promising, noninvasive approach for colorectal cancer screening; however, reliable biomarkers for detecting early-stage colon cancer (ECC) are lacking, particularly in the Chinese population. AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening. METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients, and 125 control subjects with normal colonoscopy. The cohort was randomly divided into training and test sets at a 1.5:1 ratio. Targeted bisulfite sequencing (TBSeq) was conducted on five pairs of preoperative and postop-erative sDNA samples from ECC patients to identify DNA methylation biomarkers, which were validated using pyrosequencing. By logistic regression analysis, a multiplex stool-based assay was developed in the training set, and the detection performance was further assessed in the test set and combined set. The χ2 test was used to investigate the association of detection sensitivity with clinico-pathological features. RESULTS Following TBSeq, three hypermethylated cytosine-guanine sites were selected as biomarkers, including paired box 8, Ras-association domain family 1 and secreted frizzled-related protein 2, which differed between the groups and were involved in important cancer pathways. An sDNA panel containing the three biomarkers was constructed with a logistic model. Receiver operating characteristic (ROC) analysis revealed that this panel was superior to the fecal immunochemical test (FIT) or serum carcinoembryonic antigen for the detection of ECC. We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness. In the combined set, the sensitivity, specificity and area under the ROC curve for this multiplex assay were 80.0%, 93.6% and 0.918, respectively, and the performance remained excellent in the subgroup analysis by tumor stage. In addition, the detection sensitivity did not differ with tumor site, tumor stage, histological differentiation, age or sex, but was significantly higher in T4 than in T1-3 stage tumors (P = 0.041). CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT, which could detect ECC with high sensitivity and specificity throughout the colon, showing a promising application perspective.

Heterogeneity of kidney cancer poses great challenges in clinical management. Practicians are still in need of an effective way to identify high-risk patients. Here we browsed big data from The Cancer Genome Atlas database with reference to cancer cell stemness and identified genes of interest in clear cell renal cell carcinoma. We further analyzed these genes to uncover their role in cancer promotion and progression and presented an interaction network. The results highlighted the NOTCH signaling pathway and functions related with epithelial cell migration. Finally, we managed to construct a predictive model consisting of a reasonable number of genes that successfully recognized patients at higher risk, rendering these genes suitable as subjects in future research.

Purpose: To explore the impact of family history (FH) on renal cell carcinoma (RCC) and its pathological subtype clear cell RCC (ccRCC) in a Chinese population; a significant association has previously been determined not only in familial cancer syndrome but also in sporadic cases in western populations. Methods: Consecutive patients with kidney tumors from October 2017 to May 2021 at a tertiary hospital in Shanghai were enrolled in the study. Demographic and clinical information was collected, including age, gender, FH (positive or negative, types of cancers, degree of relatives, etc.), pathological diagnosis, and Fuhrman grades. Results: A positive FH of any cancer was observed in 26.5% of the RCC patients, while only 16.8% patients with benign kidney tumor were found to have a positive FH. A strong correlation was observed between FH of any cancers in first-degree relatives and RCC (odds ratio [OR]=4.60, 95% confidence interval [CI]: 1.95-10.85, P=5.50x10-5) or ccRCC (OR=4.63, 95% CI: 1.95-11.02, P=9.63x10-5). In subgroup analysis, FH of digestive cancers was significantly associated with RCC (OR=4.42, 95% CI: 1.35-14.51, P=0.005) or ccRCC (OR=4.14, 95% CI: 1.25-13.75, P=6.84x10-4). Similar results were found in multivariate analyses. However, no significant association was observed between FH and age at onset. Conclusion: FH was an independent risk factor for RCC and ccRCC in this Chinese population. FH of any cancer in first-degree relatives and FH of digestive cancers were found to be the most significant risk factors for kidney cancers.

Primary female urethral adenocarcinoma is rare. This paper reports a case of primary urethral mucinous adenocarcinoma complicated with signet ring cell carcinoma. The patient underwent urethral tumor resection in another hospital. Postoperative examination indicated that the tumor remained, and the tumor was completely removed after urethral tumor resection. After 11 months of follow-up, there was no tumor residue or recurrence.

Abstract Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high‐throughput sequencing data revealed that JMJD6 could assemble super‐enhancers to drive a list of identity genes in kidney cancer, including VEGFA, β‐catenin, and SRC. Moreover, this JMJD6‐mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient‐derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients.

Tubulocystic renal cell carcinoma is a rare neoplasm of kidney with low metastatic tendency. There has only been a relatively small collection of literature dedicated to this subtype. Here we present two cases diagnosed in our center with detailed clinical information. Along with literature review, we aim to paint a comprehensive profile of TC-RCC. Hematuria and asthenia could be the chief complaints although most patients are asymptomatic. This lesion has a signature multilocular cystic form on radiology and enhancement of septa should reveal malignancy. Histologically, the cysts are lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium with enlarged nuclei and intermediate to large nucleoli. PAX8 and AMACR are most commonly positive while CD10 or CK7 could be focally stained in some cases. Overall, the diagnosis of TC-RCC should be based on comprehensive clinical and molecular results because early determination of the lesion could prelude a timely intervention and favorable prognosis.