Background: It is necessary to identify valuable predictors of primary lymph node metastasis and prognosis for patients with synchronous colorectal cancer liver metastases (CRLM) with simultaneous resection of colorectal cancer (CRC) and liver metastases. This study constructed nomograms especially incorporating preoperative testing markers to predict primary lymph node metastases and prognosis in CRLM patients.Methods: By the highest Youden index (sensitivity + 1-specificity), the optimal cut-off values of testing markers for postoperative major complications and lymph node metastasis were identified. Multivariate regression analysis was used to reveal independent predictors for primary lymph node metastasis, postoperative major complications and progression-free survival (PFS). Nomograms based on independent predictors were constructed, and the discrimination and calibration were evaluated. Results: A nomogram predicting primary lymph node metastasis was based on four risky independent predictors: American Society of Anesthesiologists (ASA) score 3-4, preoperative albumin (ALB) <41.15 g/L, poor differentiation and multiple liver metastases. The performance of the model was acceptable in predicting lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.655 (95% CI: 0.591-0.739). Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 13.26, P=0.815). In the multivariate analysis, preoperative lactate dehydrogenase (LDH) ≥202.5 U/L [odds ratio (OR) =2.084, 95% confidence interval (CI): 1.039-4.181, P=0.039] and operation time ≥350.5 min (OR =2.848, 95% CI: 1.418-5.723, P=0.003) were independently associated with the presence of postoperative major complications. A nomogram predicting PFS was constructed based on poor differentiation, positive lymph node metastasis, bilobar liver distribution and R0 resection with good discrimination (C-index: 0.656±0.021) and calibration.Conclusions: This study established predictive nomograms specifically incorporating preoperative ALB and LDH levels for the prediction of primary lymph node metastasis and prognosis in synchronous CRLM patients with simultaneous resection, which have favourable discrimination and calibration to make individualized predictions.

Background Colorectal cancer (CRC) is one of the most common malignancies, and it’s expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. Methods Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. Results Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. Conclusions These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.

Background: This study sought to evaluate the effects of pre-neoadjuvant chemotherapy lactate dehydrogenase (pre-NAC LDH) levels, preoperative LDH levels, and changes in LDH levels on the pathological response and outcomes of colorectal liver metastases (CRLM) patients treated with liver resection after NAC.Methods: This study included 152 colorectal CRLM patients, who underwent NAC followed by liver resection. Patients were excluded if they were diagnosed with other malignancies or lacked follow-up and clinical data. Demographic and clinicopathological data were collected from hospital records. Pathological response and postoperative complications were measured according to the tumor regression grade (TRG) and Clavien-Dindo classification system, respectively. The optimal cutoff values were determined by the receiver operating characteristic curve and the X-tile analysis. Changes in LDH levels were graded as 0, 1, and 2. A logistic regression analysis was conducted to identify the independent predictors of pathological response and postoperative major complications. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors of progression-free survival (PFS) and overall survival (OS). Results: The multivariate analysis indicated that a grade 2 LDH level change was a risk factor of an unfavorable histological response [odds ratio (OR) 0.249, 95% confidence interval (CI): 0.066-0.942; P=0.041] and major postoperative complications (OR 2.523, 95% CI: 1.179-10.530; P=0.024), which were independent of other clinical covariates. A pre-NAC LDH level ≥145 IU/L [hazards ratio (HR) 0.584, 95% CI: 0.359-0.950; P=0.030], a grade 1 LDH level change (HR 0.584, 95% CI: 0.359-0.950; P=0.030) and a grade 2 LDH level change (HR 0.447, 95% CI: 0.231-0.864; P=0.017) were independent prognostic predictors of PFS. A preoperative a LDH level ≥231 IU/L (HR 0.405, 95% CI: 0.192-0.852; P=0.017) and a grade 2 LDH level change (HR 0.362, 95% CI: 0.157-0.834; P=0.017) were independent prognostic factors of OS, which were independent of other clinical covariates.Conclusions: LDH levels and changes in LDH levels are potentially useful biomarkers for predicting the pathological response and prognosis of CRLM patients receiving NAC followed by liver resection.