Search results
Through a systematic literature search, we primarily identified a total of 139 articles. After removal of 92 duplicate publications, 47 articles remained. We further excluded 7 articles by browsing the titles and abstracts. 39 articles explored the prognostic role of LCR in cancers. However, 11 were not suitable for inclusion criteria. Finally, we identified 31 studies from 29 articles published between 2020 and 2023 [14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44]. The flow diagram of the literature search was shown in Fig. 1.
Study characteristics
The total number of patients in the included articles was 11429 (range: 48–1303 patients).13 studies were produced in China, 15 studies were conducted in Japan, and three other studies were conducted in Turkey. 29 studies reported OS data, 12 studies displayed DFS data, 7 studies covered RFS, 3 studies presented PFS data and 3 studies revealed CSS data. A total of 10 types of tumors were included, such as gastric cancer(GC), colorectal cancer(CRC), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma(ICC), pancreatic cancer(PC), esophageal cancer(EC), breast cancer(BC), lung cancer(LC), soft tissue sarcoma(STS) and osteosarcoma. The NOS scores of the included studies ranged from 6 to 8 (mean: 6.74). The basic study data are shown in Table 1.
Table 1
Basic information of included studies
Study | Year | Country | Study type | Tumor type | Sample | Treatment methods | Analysis type | Survival analysis | NOS score |
Angin | 2021 | Turkey | R | GC | 123 | Surgery | Univariate | OS | 6 |
Aoyama | 2022 | Japan | R | GC | 480 | Surgery | Multivariate | OS,RFS | 7 |
Cheng | 2020 | China | R | GC | 607 | Surgery | Multivariate | OS,DFS | 7 |
Eren | 2022 | Turkey | R | CRC | 102 | Surgery | Multivariate | OS,DFS | 7 |
He | 2020A | China | R | LC | 753 | Mixed | Multivariate | OS,DFS, PFS | 7 |
He | 2020B | China | R | LC | 252 | Mixed | Multivariate | OS,DFS, PFS | 7 |
Hu | 2020 | China | R | osteosarcoma | 137 | Surgery | Multivariate | OS | 6 |
Iseda | 2021 | Japan | R | HCC | 306 | Surgery | Multivariate | OS,RFS | 7 |
Iseda | 2022 | Japan | R | PC | 97 | Surgery | Multivariate | OS,RFS | 7 |
Mei | 2021 | China | R | HCC | 442 | Anti-PD-1 Therapy | Univariate | OS | 6 |
Nakamura | 2021 | Japan | R | CRC | 756 | Chemotherapy | Multivariate | OS | 6 |
Nakamura | 2022 | Japan | R | STS | 132 | Surgery | Multivariate | DSS,EFS | 7 |
Nakamura | 2022 | Japan | R | CRC | 433 | Surgery | Multivariate | OS | 6 |
Ni | 2022 | China | R | HCC | 290 | Surgery | Multivariate | OS,DFS | 7 |
Nishi | 2021 | Japan | R | CRC | 48 | Surgery | Univariate | OS,DFS | 6 |
Noguchi | 2021 | Japan | R | ICC | 60 | Surgery | Multivariate | DSS | 6 |
Okugawa | 2020 | Japan | R | GC | 551 | Surgery | Multivariate | OS,DFS | 7 |
Okugawa | 2021 | Japan | R | CRC | 307 | Surgery | Multivariate | OS,DFS | 7 |
Ou | 2021 | China | R | CRC | 955 | Surgery | Multivariate | OS,CSS | 7 |
Takeuchi | 2021 | Japan | R | EC | 495 | Surgery | Multivariate | OS,RFS | 7 |
Tsujiura | 2022 | Japan | R | GC | 103 | Surgery | Multivariate | OS,RFS | 7 |
Utsumi | 2022 | Japan | R | CRC | 104 | Surgery | Multivariate | OS,RFS | 7 |
Wang | 2022 | China | R | BC | 375 | Surgery | Multivariate | OS,DFS | 7 |
Utsumi | 2022 | Japan | R | HCC | 173 | Surgery | Multivariate | OS,RFS | 7 |
Xiong | 2022A | China | R | GC | 575 | Surgery | Multivariate | OS,DFS | 7 |
Xiong | 2022B | China | R | GC | 774 | Surgery | Multivariate | OS,DFS | 7 |
Matsunaga | 2023 | Japan | R | GC | 101 | Chemotherapy | Univariate | OS | 6 |
Yang | 2022 | China | R | ICC | 73 | Anti-PD-1 Therapy | Univariate | OS | 6 |
Yilmaz | 2022 | Turkey | R | LCC | 162 | Chemo-radiotherapy | Multivariate | OS, PFS | 7 |
Suzuki | 2020 | Japan | R | CRC | 1303 | Surgery | Multivariate | OS,DFS | 7 |
Sugawara | 2022 | Japan | R | EC | 360 | Surgery | Univariate | OS | 6 |
Abbreviations: GC, gastric cancer; CRC, colorectal cancer; HCC, hepatocellular carcinoma;, ICC, cholangiocarcinoma PC, pancreatic cancer; EC, esophageal cancer; BC, breast cancer; LC, lung cancer; STS, soft tissue sarcoma; R, retrospective; OS, overall survival; DFS, disease-free survival; RFS, recurrence free survival; PFS, progression-free survival; CSS, cancer-specific survival;
Association between high LCR and OS
29 studies from 27 articles involving 11237 patients explored the association between LCR and prognosis using OS. We used a fixed model to calculate the pooled HRs owing to moderate heterogeneity (I2 = 46.7%). The results of the meta-analysis revealed that high LCR was significantly related to beneficial OS (HR:0.51,95% CI: 0.48–0.55). The forest plot was displayed in Fig. 2.
Subgroup analysis for OS
We further conducted subgroup analyses based on cancer type, analysis type, treatment and country. The results were shown in Table 2. We found that high LCR was an favorable prognostic marker in GC (HR: 0.45; 95% CI: 0.39–0.53), CRC(HR:0.56; 95% CI: 0.50–0.62), HCC (HR:0.60; 95% CI:0.49–0.73),LC(HR:0.48,95%CI:0.33–0.71) and EC (HR:0.42; 95% CI: 0.34–0.54). In terms of digestive or non-digestive system cancers, high LCR indicated good OS. Moreover, we also found that high LCR was associated with favorable OS for the Japan group (HR: 0.48; 95% CI:0.43–0.54), China group (HR: 0.48; 95% CI: 0.40–0.58) and Turkey group (HR:0.41; 95% CI: 0.30–0.56). Overall, high LCR predicted good OS regardless of any subgroup.
Table 2
Stratified study | No of studies | Pool HR(95% CI) | P-value | Heterogeneity I2(%) | P | Model |
Cancer type | | | | | | |
GC | 7 | 0.45(0.39–0.53) | <0.01 | 0 | 0.71 | Fxed |
CRC | 8 | 0.56(0.50–0.62) | <0.01 | 40.9 | 0.106 | Fixed |
HCC | 4 | 0.60(0.49–0.73) | <0.01 | 0 | 0.71 | Fixed |
LC | 3 | 0.48(0.33–0.71) | <0.01 | 69.5 | 0.025 | Random |
EC | 3 | 0.42(0.34–0.54) | <0.01 | 42.6 | 0.175 | Fixed |
Other cancers | 4 | 0.25(0.17–0.38) | <0.01 | 25.3 | 0.26 | Fixed |
Digestive system cancers | 24 | 0.52(0.48–0.56) | <0.01 | 47.30% | 0.006 | Fixed |
Non-digestive system cancers | 5 | 0.45(0.33–0.61) | <0.01 | 55 | 0.064 | Random |
Analysis type | | | | | | |
Univariate analysis | 6 | 0.43(0.31–0.60) | <0.01 | 59.90% | 0.029 | Random |
Multivariate analysis | 23 | 0.52(0.48–0.56) | <0.01 | 44.4 | 0.012 | Fixed |
Treatments | | | | | | |
Surgery | 22 | 0.51(0.47–0.56) | <0.01 | 37.1 | 0.042 | Fixed |
No-surgery | 7 | 0.46(0.36–0.59) | <0.01 | 68.6 | 0.004 | Random |
Country | | | | | | |
Japan | 15 | 0.48(0.43–0.54) | <0.01 | 17.6 | 0.257 | Fixed |
China | 11 | 0.48(0.40–0.58) | <0.01 | 65.40% | 0.001 | Random |
Turkey | 3 | 0.41(0.30–0.56) | <0.01 | 0 | 0.622 | Fixed |
Abbreviations: GC, gastric cancer; CRC, colorectal cancer; HCC, hepatocellular carcinoma;, EC, esophageal cancer; LC, lung cancer;
Association between high LCR and DFS
12 studies from 10 articles involving 5937 patients documented the association between high LCR and prognosis of cancers using DFS. We used a random model to calculate the pooled HRs because of the obvious heterogeneity (I2 = 72.1%). The results showed that high LCR was correlated with good DFS (HR: 0.55; 95% CI: 0.43–0.70). The forest plot was illustrated in Fig. 3. We further performed subgroup analysis(Table 3). The results showed that high LCR was closely related to the subgroups of GC (HR: 0.46, 95% CI: 0.38–0.55), CRC (HR: 0.43, 95% CI: 0.20–0.91), digestive system cancers (HR: 0.50,95% CI: 0.39–0.65), surgery (HR: 0.50,95% CI: 0.39–0.64) and multivariate analysis (HR: 0.55, 95%CI: 0.43–0.71). In subgroup analysis based on countries, high LCR revealed good DFS.
Table 3
Subgroup analysis for DFS
Stratified study | No of studies | Pool HR(95% CI) | P-value | Heterogeneity I2(%) | P | Model |
Cancer type | | | | | | |
GC | 3 | 0.46(0.38–0.55) | <0.01 | 17.9 | 0.3 | Fixed |
CRC | 4 | 0.43(0.20–0.91) | 0.027 | 78.5 | 0.003 | Random |
LC | 2 | 1.01(0.73–1.38) | 0.963 | 19.9 | 0.264 | Fixed |
Other cancers | 2 | 0.61(0.46–0.80) | 0.001 | 0.00% | 0.396 | Fixed |
Digestive system cancers | 9 | 0.50(0.39–0.65) | <0.01 | 68.50% | 0.001 | Random |
Non-digestive system cancers | 3 | 0.77(0.45–1.31) | 0.332 | 60.7 | 0.079 | Random |
Analysis type | | | | | | |
Univariate analysis | 1 | 0.58(0.13–2.58) | | | | |
Multivariate analysis | 11 | 0.55(0.43–0.71) | <0.01 | 74.60% | <0.01 | Random |
Treatment method | | | | | | |
Surgery | 10 | 0.50(0.39–0.64) | <0.01 | 64.9 | 0.002 | Random |
Mixed | 2 | 1.01(0.73–1.38) | 0.96 | 19.9 | 0.264 | fixed |
Country | | | | | | |
China | 7 | 0.56(0.41–0.76) | <0.01 | 74.50% | <0.010 | Random |
Turkey | 1 | 0.09(0.029–0.28) | | | | |
Japan | 4 | 0.71(0.58–0.86) | 0.001 | <0.01 | 0.635 | Fixed |
Abbreviations: GC, gastric cancer; CRC, colorectal cancer; LC, lung cancer;
Association between high LCR and RFS
7 studies involving 1758 patients investigated the association between high LCR and prognosis using RFS. The results displayed that high LCR was significantly associated with good prognosis (HR:0.57; 95% CI 0.48–0.67)(Fig. 4)
Association between high LCR and CSS and PFS
3 studies analyzed the association between high LCR and CSS. In addition, 3 studies examined the association between high LCR and PFS. The results showed that high LCR was significantly associated with good CSS (HR: 0.53,95% CI: 0.42–0.67) (Fig. 5) and PFS(HR:0.50, 95%CI: 0.27–0.92)(Fig. 6).
Sensitivity analysis
Sensitivity analysis was implemented by removing one study. The results were consistent with the comprehensive analysis, confirming that the outcomes of the combined OS, DFS and RFS were stable(Fig. 7).
Publication bias
Begg’s test and Egger’s test were used to evaluate the publication bias. P value of Begg’s test and Egger’s test was 0.016 and 0 for OS(Fig. 8A), respectively. There was a degree of publication bias, however, we found that the overall results were not affected through the trim-and-fill method (HR:0.473,95%CI:0.424–0.528). P values of Begg’s and Egger’s tests were 0.451 and 0.247 for DFS, respectively (Fig. 8B). P values of Begg’s and Egger’s tests were 1 and 0.546 for RFS, respectively (Fig. 8C). P was more than 0.05 and no significant bias was observed.