There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra-and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer cell proliferation and tumorigenesis. Our findings reveal a mechanism of LIN28B activation in cancer and the potential utility of LIN28B-TST for clinical purposes.

Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor‐specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues. Many of the TSTs were found to be unannotated and noncoding RNAs. We observed that intergenic TSTs are generated from transcription initiation sites frequently harboring long terminal repeat (LTR) elements. The strong presence of TSTs indicates significantly poor prognoses in HCC. Functional screening revealed a noncoding TST (termed TST1), which acted as a regulator of HCC cell proliferation and tumorigenesis. TST1 is generated from an LTR12C promoter regulated by DNA methylation and retinoic‐acid–related drugs. Additionally, we observed that TSTs may be detected in the blood extracellular vesicles of patients with HCC. Conclusion: Our findings suggest an abundance of TSTs in HCC and their potential in clinical settings. The identification and characterization of TSTs may help toward the development of strategies for cancer diagnosis and treatment.

Vitamin D status has been shown to be positively correlated with the morbidity and prognosis of colorectal cancer (CRC) patients. However, the prognostic effect of vitamin D status on patients with stage II and III CRC, especially Asian patients, remains unclear. A total of 728 patients (523 in the primary cohort and 205 in the validation cohort) who were diagnosed with stage II-III CRC between January 2011 and December 2015 were enrolled. Their serum 25-hydroxyvitamin D3 [25(OH)D] levels were tested. Kaplan-Meier curves and Cox regression analyses were carried out. Subgroup analyses were conducted according to tumor location. In the primary cohort, the serum 25(OH)D level was positively correlated with the overall survival (OS) of all CRC patients (p= 0.016) and stage III patients (p= 0.009), while no correlation was found between 25(OH)D level and the prognosis of patients with stage II CRC. Moreover, 25(OH)D level was an independent prognostic factor for the OS of all patients with CRC [HR 0.541, 95% CI 0.334–0.875, p=0.012] and those with stage III CRC (HR 0.563, 95% CI 0.319–0.993, p=0.047). Subgroup analysis indicated that only in the left-sided subgroup, stage III CRC patients with high 25(OH)D levels had better OS than those with low 25(OH)D levels (HR 0.474, 95% CI 0.230–0.978, p=0.043). In the validation cohort, serum 25(OH)D levels were verified to have prognostic value for patients with stage III CRC (HR 0.220, 95% CI 0.080–0.602, p=0.003), and low 25(OH)D levels indicated worse OS for left-sided stage III CRC patients (HR 0.233, 95% CI 0.075–0.727, p=.012). In conclusion, vitamin D status is positively correlated with the survival of CRC patients, especially those with left-sided stage III CRC.