High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

Low ferroptosis score predicts chemotherapy responsiveness and immune-activation in colorectal cancer.

BACKGROUND: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro-environmental distributions. METHODS: Immunohistochemical staining was performed for CRC patients' tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan-Meier analysis and cox analysis. RESULTS: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C-index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN-γ was potentially the central molecule at the crossroad between ferroptosis and onco-immune response. CONCLUSION: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune-supportive responses and IFN-γ was the central molecule for this process.

Combined test of third lumbar skeletal muscle index and prognostic nutrition index improve prognosis prediction power in resected colorectal cancer liver metastasis.

BACKGROUND: In this paper, we aim to explore clinical value of skeletal muscle index (SMI) and prognostic nutrition index (PNI) on resected colorectal cancer liver metastasis (CRLM). RESULTS: Among the 539 patients, 355 were males. Baseline lower SMI was associated with smaller BMI, smaller PNI, smaller pre-albumin and longer hospitalization days (P<0.05). Patients with lower SMI and PNI had significantly shorter duration of PFS and OS (P<0.05). SMI can reflect the postoperative treatment response. Postoperative 6-month's and 12-month's SMI and PNI can indicate overall prognosis. When combined SMI and PNI, prognostic AUC of ROC curves improved significantly. CONCLUSION: Combined monitor of SMI and PNI can improve the power at predicting prognosis. Postoperative 6-month's record of SMI and PNI was more accurate and predictive for CRLM prognosis. METHOD: A total of 539 resected CRLM patients between January 2013 to December 2016 with complete clinical data were included. Computed tomography image was collected from each patient. Receiver-operating characteristic (ROC) curves were constructed; area under curves (AUC) were also determined. All clinical variables were analyzed in proper way.

Exploration of exact significance of lymph node ratio and construction of a novel stage in colon cancer with no distant metastasis.

AIM: Lymph node ratio (LNR) seems to be more precise than classic N stage in classifying cancer stage. Thus, we aim to construct a modified classification system based on LNR for colon cancer without distant metastasis. METHODS: This study enrolled two independent cohorts of patients. The primary cohort enrolled 2,152 patients from 2008 to 2013 in Zhongshan Hospital, Fudan University. The validation cohort consisted of 77,406 patients from the Surveillance, Epidemiology, and End Results (SEER) registry from 2004 to 2014. The inclusion criteria were: pathologically confirmed colon cancer, and American Joint Committee on Cancer (AJCC) stage I/II/III. The exclusion criteria included: incomplete follow-up information, rectal cancer, and multiple primary sites. The prognostic value of LNR for overall survival was evaluated. The cutoff value of LNR was determined by the X-tile. Predictive performance of modified classification was determined by the concordance index. RESULTS: After analysis, 0.05 and 0.50 were determined as the best threshold values of LNR. A value of <0.05, 0.05-0.50 and >0.50 was reclassified as the mN0, mN1 and mN2 stage. A modified classification based on mN0, mN1, and mN2 was further constructed for stage I/II/III colon cancer. C-index of the modified classification was statistically more precise than AJCC classification (0.687 versus 0.605, P<0.001). The same results can also be determined in the validation cohort (0.715 versus 0.640, P<0.001). Furthermore, a prognostic nomogram including independent factors was constructed. The constructed nomogram showed good performance according to the calibration curve. CONCLUSION: The clinical value of LNR level was preferable to classic N stage in colon cancer patients. Our proposed classification based on LNR and AJCC T category can effectively differentiate patients with varied survival outcomes.

[Current situation and countermeasures of two-way referral between wound healing department and community health system].

This study analyzed the current situation and problems of two-way referral between wound healing department of general hospitals and community health service centers through stipulated interview with physicians in general hospitals and community health service centers, and patients visiting these organizations from March 2011 to April. It was found that the current two-way referral process for wound repair were facing a series of problems, including hospitals-transfer difficulty, incomplete two-way referral policy and undefined practice protocol, information-sharing obstacle between general hospitals and community health service centers. The critical countermeasures for overcoming these obstacles in two-way referral of wound ailments shall include construction of further linkage mechanism among all levels of hospitals, establishment of the drug-obtaining mechanism, establishment of an explicit two-way referral process of wound repair, and establishment of a database of diagnosis and treatment information of patients that can be accessed by doctors of different levels of hospitals, etc.