The predictive value of CD4, CD8, and C-reactive protein in the prognosis of schistosomal and non-schistosomal colorectal cancer.

BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China and occasional outbreaks occur in Europe in recent years. The relationship between inflammation caused by Schistosoma japonicum and colorectal cancer (CRC) is still obscure, and the inflammation based prognostic systems of schistosomal colorectal (SCRC) has rarely been reported. AIM: To explore the different roles of tumor infiltrating lymphocytes (TILs) and C-reactive protein (CRP) in SCRC and in Non-schistosomal CRC (NSCRC), providing a possible predictive system to evaluate outcomes and to improve the risk stratification for CRC patients, especially for CRC patients with schistosomiasis. METHODS: Three hundred fifty-one CRC tumors were evaluated for density of CD4 + , CD8 + T cells and CRP in intratumoral and stromal compartments by immunohistochemical using tissue microarray. RESULTS: There were no association between TILs and CRP and schistosomiasis. Multivariate analysis identified stromal CD4 (sCD4) (p = 0.038), intratumoral CD8 (iCD8) (p = 0.003), schistosomiasis (p = 0.045) as independent prognostic factors for overall survival (OS) in the whole cohort; and sCD4 (p = 0.006) and iCD8 (p = 0.020) were independent prognostic factors for OS in the NSCRC and SCRC set, respectively. Besides, we found that there were no differences of TILs and CRP, which were distributed in different areas of tumor tissue, between CRC patients with and without schistosomiasis. CONCLUSION: The results remind us that different subtypes of TILs have distinguished biological behavior and prognosis value in the immune microenvironment of NSCRC and SCRC patients. Meanwhile, the findings require us to stratify patients with schistosomiasis and this might facilitate patient counseling and management.

Comparison of the prognostic value of stromal tumor-infiltrating lymphocytes and CD3 + T cells between schistosomal and non-schistosomal colorectal cancer.

AIM: To compare the prognostic value of tumor-infiltrating lymphocytes (TILs) and CD3 + cells and CD20 + cells between schistosomal colorectal cancer (SCRC) and non-schistosomal CRC (NSCRC). BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China, and occasional outbreaks occur in Europe recently. The role of immune cells in the immune microenvironment of SCRC and NSCRC is remaining obscure, and the inflammation-based prognostic systems of SCRC has rarely been reported. METHODS: HE-stained sections of 349 colorectal cancer (CRC) tumors, which were completely resected, were evaluated for density of TILs. Meanwhile, we evaluated CD3 + T lymphocytes and CD20 + B lymphocytes by immunochemistry. The relationship of these infiltrating immune cells with clinicopathological features, including schistosomiasis, and clinical outcomes was evaluated, and the prognostic roles of TILs in SCRC and NSCRC were explored. RESULTS: Except for age (P < 0.0001), there were no significant differences between NSCRC and SCRC patients in clinicopathological features (P > 0.05). Beside, the positive expression pattern of sTILs, iTILs, CD3, and CD20 between NSCRC and SCRC patients was also similar (P > 0.05). In the whole cohort, sTILs and CD3 were defined as independent prognostic factors (P = 0.031 and P = 0.003, respectively). CD3 was an independent prognostic factor both in the NSCRC and SCRC set (P = 0.026 and P = 0.045, respectively). Higher sTILs, CD3, and CD20 were correlated with less aggressive tumor characteristics in the whole cohort and in subgroups. CONCLUSION: Although CD3 was an independent prognostic factor for both NSCRC and SCRC set, there were no significant differences between SCRC and NSCRC patients in sTILs, CD3, CD20, and in other clinicopathological features.

Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer.

BACKGROUND: The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. METHODS: Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. RESULTS: In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). CONCLUSIONS: The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer.

OBJECTIVE: The purpose of this study was to explore the prognostic role of c-MYC amplification in colorectal cancer, particularly in schistosomiasis-associated colorectal cancer. METHODS: Three hundred and fifty four cases of colorectal cancer, which were from Qingpu Branch of Zhongshan Hospital affiliated to Fudan University, were retrospectively analyzed in a tissue microarray (TMA) format, with fluorescence in situ hybridization (FISH) assay and immunohistochemistry (IHC). RESULTS: c-MYC gene amplification was found in 14.1% (50 out of 354) of patients with colorectal cancer and was correlated with old age (P = 0.028), positive lymph node metastasis (P = 0.004) and advanced stage tumors (P = 0.002). The overexpression of c-MYC was closely associated with the amplification status (P = 0.023). Kaplan-Meier survival curves for overall survival (OS) showed a statistically significant difference for patients with c-MYC amplification in full cohort of colorectal cancer, stage III-IV set and patients with lymph node metastasis (P = 0.002, 0.034, 0.012, respectively). Further analysis found c-MYC amplification associated with poorer survival in the subgroup of colorectal cancer with schistosomiasis (CRC-S, P < 0.001), but not in colorectal cancer without schistosomiasis (CRC-NS, P = 0.155). By multivariate analysis, c-MYC amplification was an independent poor-prognostic factor in CRC-S set (P = 0.046). CONCLUSIONS: Our study firstly found c-MYC amplification could predict poor prognosis in schistosomiasis-associated colorectal cancer, but not in colorectal cancer without schistosomiasis.

Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer.

AIM: The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients' clinical outcomes. METHODS: Three hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. RESULTS: Colorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III-IV tumors and in patients with lymph node metastasis, but not in patients with stage I-II tumors and in patients without lymph node metastasis. CONCLUSION: Schistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III-IV tumors or patients with lymph node metastasis.